Advances in Virus Research

Published by Elsevier
Online ISSN: 0065-3527
Publications
Article
This chapter presents studies on the pathogenicity and pathogenesis of Japanese encephalitis (JE) virus in China. In China, the disease is very widespread. Practically all provinces except the two most western ones, Xinjiang and Xizang, have the disease. Based on studies on the pathogenic properties of different virulence strains of JE virus, on the variation of virus virulence in mice and tissue culture, and on the ecology of JE virus, a hypothetical sketch on the possible origin of emergence of virus strains with different virulence is deduced. It indicates that a mosquito-pig, duck-mosquito cycle is responsible for the origin of high virulence virus strains. In the years after 1949, the morbidity rate (cases/100,000) for JE in Beijing was between 15 and 25. In recent years, the morbidity rate in Beijing has been reduced to around 2.5, in spite of the fact that rice fields, a good breeding place for the vector C. tritaeniorrhynchus, have been greatly increased. The reduction in the morbidity rate is attributed primarily to the effect of mass immunization of children under 10 and partly to the antimosquito campaign and virus vaccines.
 
Article
This chapter discusses the possible evolutionary significance of viroids as well as speculates as to their place within the biological universe. Recognition of the fundamental disparity between viruses and viroids became possible only after the establishment of certain basic principles of virology and molecular biology. These principles helped create an intellectual milieu in which the existence of free nucleic acid pathogens could not a priori be ruled out. A few plant virologists and molecular biologists recognized the potential significance of the viroid, not only for plant pathology but also for cell and molecular biology and decided to become active in the field. This led to healthy competition and a substantial acceleration of research. Comparative examination of viroid sequences reveals that some variants may have originated as a result of point mutations or sequence duplications/deletions. Others apparently originated because of recombination phenomena among different viroids. As is the case with plant viruses, viroid entry into host cells is a passive process. The required penetration of the cell wall is achieved by either appropriate wounding or direct injection into cells by insects or other vectors.
 
Article
Kaposi's sarcoma-associated herpesvirus (KSHV) is the eighth human herpesvirus (HHVS) and is the subject of considerable interest because of its association with several major acquired immunodeficiency syndromes (AIDS)-related malignancies. Epidemiologic studies now largely agree that this virus is the required infectious cofactor responsible for Kaposi's sarcoma (KS) and related neoplastic disorders. Although the virus is important from a clinical and a public health standpoint, it also promises to provide a surprisingly rich source of basic information on how viruses induce cellular proliferation. As with other tumor viruses, there are also a number of important obstacles to the study of KSHV. Although KSHV can be cultured to high titer in naturally infected lymphoma cell lines, the virus cannot be sustainably cultivated from KS lesions analogous to Epstein-Barr virus (EBV or human herpesvirus 4/HHV4) in nasopharyngeal carcinoma.
 
Article
Progress during the past several years, has resulted in the elucidation of the mechanism of replication of a variety of bacterial and animal viruses. The sequence of events leading to the formation of complete virus particles has been described in considerable detail through the analysis of virus gene products at various stages during the infectious cycle. Most of the early advances were made by studying the intracellular localization and synthesis of the structural components of the viruses. In the case of RNA tumor viruses, very little is known about the mechanism of replication of these agents. Although it has been well established that the particles mature at the cell surface, it is not understood how and where the individual nucleic acid and protein components are synthesized. Recently, a great deal of information has been obtained about the various structural components of the virus particle. It is the purpose of this chapter to bring this information into focus and to indicate how these materials are being utilized to study the expression of the virus genome in the host cell.
 
Article
This chapter discusses the specific features of an outbreak of poliomyelitis comprising nine paralytic cases and one nonparalytic case that occurred in Finland. The chapter presents detailed background information on the history of poliomyelitis and antipolio immunizations in Finland before this outbreak. Several lessons can be learned from this limited outbreak and from recent research in poliovirus epidemiology and immunology. Although the uncommon antigenic properties of the P3/Finland/84 strains were certainly not the only reason for the outbreak, this episode should justify international efforts to thoroughly characterize the range of antigenic variation among the currently circulating poliovirus strains. There is evidence that the genetic variation found among poliovirus strains is not only temporally but also geographically determined. Although this episode in Finland would not require other explanations besides the uncommon antigenic properties of the epidemic type 3 poliovirus strains and the consistent use of the relatively weakly immunogenic IPV preparation, this incident should also be taken as a warning for the unexpected drawbacks in vaccine-induced immunity. Humans vary in their capacity to respond to individual antigenic sites. Thus, a single antigenic site may not be enough for use as a vaccine in humans if a significant proportion of people happen to be poor responders to this particular site.
 
Article
In 1959, 5-iodo-2'-deoxyuridine (IDU) was described, the first antiviral drug ever to be (and still) marketed (for the topical treatment of herpetic keratitis). Now 50 years following the description (of the synthesis) of IDU, we have 50 compounds on the market that have been licensed for clinical use in the treatment of virus infections. Of those 50, exactly 25 have been formally approved as anti-HIV drugs; the other 25 have been formally approved for the treatment of other virus infections: herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), hepatitis B virus (HBV), hepatitis C virus (HCV), and influenza virus infections.
 
Article
Partitiviruses constitute one of the nine currently recognized families of viruses with encapsidated, double-stranded (ds)RNA genomes. The partitivirus genome is bisegmented, and each genome segment is packaged inside a separate viral capsid. Different partitiviruses infect plants, fungi, or protozoa. Recent studies have shed light on the three-dimensional structures of the virions of three representative fungal partitiviruses. These structures include a number of distinctive features, allowing informative comparisons with the structures of dsRNA viruses from other families. The results and comparisons suggest several new conclusions about the functions, assembly, and evolution of these viruses.
 
Article
The precision of molecular biology has allowed a better definition of the components of the Abelson system. We know the gene structures and gene products for the cellular and viral forms of this family of related tyrosine kinases. However, many basic issues first identified in the early biological observations of Abelson, Rabstein, and others remain unanswered. The precise pathway for transformation in biochemical terms remains unknown for Ab-MLV and all of its relatives. Relatively little can be said to explain the preferential growth stimulation for certain hematopoietic cell types by the viral and other altered forms of the oncogene, and no clear insights into the function of the normal cellular forms of the abl oncogene are available. Future progress will certainly depend on the intensive efforts by many workers in the broader field of cellular growth control mechanisms.
 
Article
The horse (Equus caballus) is unusual, in that it is host to three distinct alphaherpes viruses, designated as equine herpesvirus 1 (EHV1; equine abortion virus), EHV4 (equine rhinopneumonitis virus), and EHV3 (equine coital exanthema virus). EHV4 and EHVl are closely related viruses that, prior to 1981, were considered a single virus type or subtypes of a single virus. There was an assumption that this single virus, “EHV1,” caused an acute respiratory tract disease called “rhinopneumonitis,”which established a latent infection and then, as an unpredictable sequel in the case of a pregnant mare, underwent reactivation followed by viremic spread to the fetus, causing abortion. This chapter is concerned primarily with EHV4 and EHV1, with brief consideration of AHV3, highlighting its relationship to EHV1. Earlier, the reviews of “EHV1” may be consulted for a historic perspective and earlier references. However, each of these reviews carries ambiguities related to a belief that only a single virus type “EHV1,” rather than two distinct viruses, was involved. This chapter mainly focuses on the advances in our understanding of the molecular biology, including genetic and antigenic characteristics, of EHV4 and EHVl since 1981. A brief overview of the clinical syndromes and pathogenesis, epidemiology, laboratory diagnosis, vaccines, and immunity of EHV4 and EHVl is also given in this chapter.
 
Article
The chapter discusses the various properties of the adenoviruses, such as the nature of virion and the controlling factors in the productive or abortive infection. The dissection of the virion and its component parts, summarized in this chapter, has provided essential markers for the exploration and correlation of these biological variables, the mapping of phage chromosomes, based on deletions in conditional lethal mutants, required the structural and functional identification of phage precursors and subunits, such that each identifiable moiety of the adenovirion will help in relating biological activity to structural and molecular properties of the viral genomes. For a full understanding of the biology of adenovirus infection, as of other virus-cell systems, it is important to recognize that uniformity and synchrony of response is a deliberately created experimental artifact resulting only from high multiplicity infection of competent cells. This type of response may be absent in natural infections, which does not occur under conditions of low multiplicity infection, and may be fundamentally irrelevant in adenoviral tumorigenesis and abortive infection. For the sake of simplicity, any infection with complete adenovirus particles not leading to production of infectious progeny will be defined as “abortive.” The term “complete” in this context, implies that the same virions can induce productive infection in some suitable indicator cell. Hence, these viruses can be characterized, operationally, as host dependent conditionally lethal, either the permissive host cell supplies some function needed for virus replication that the non permissive cell lacks, or the latter imposes a restriction not present in the permissive one. Both alternatives could, in a purely descriptive way, satisfy the need for working hypotheses to explain the various examples of abortive infection with adenoviruses.
 
Article
Tumor induction in rodents by human adenovirus type 12 (Ad12), one of the classical systems for studies in DNA viral oncology still presents numerous riddles and opportunities for the researcher in molecular biology. The mechanism of DNA virus transformation is not generally understood because many functions exist that may be responsible for the transformation event. These functions could be virus-encoded or cellular functions that are activated or modified in their activity as a consequence of interactions with viral proteins. The chapter studies the abortive interaction of Ad12 with hamster cells under the premise that an improved understanding of viral gene activities at early and late times after the infection of hamster cells may be intimately related to the transformation event. Ad12 does not replicate in hamster cells, and the block in this aborted replication cycle lies prior to viral DNA replication. Ad12 virions can enter the cytoplasm, Ad12 DNA reaches the nucleus, and viral DNA can integrate into the cellular genome.
 
Article
The Gammaherpesvirinae subfamily of herpesviruses comprises lymphotropic viruses, including the oncogenic human pathogens Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus. During lytic infection, gammaherpesviruses manipulate host gene expression to optimize the cellular environment for viral replication and to evade the immune response. Additionally, although a lytically infected cell will itself be killed in the process of viral replication, lytic infection can contribute to pathogenesis by inducing the secretion of paracrine factors with functions in cell survival and proliferation, and angiogenesis. The mechanisms by which these viruses manipulate host gene expression are varied and target the accumulation of cellular mRNAs and their translation, signaling pathways, and protein stability. Here, we discuss how gammaherpesviral proteins directly influence host mRNA biogenesis and stability, either selectively or globally, in order to fine-tune the cellular environment to the advantage of the virus. Appreciation of the mechanisms by which these viruses interface with and adapt normal cellular processes continues to inform our understanding of gammaherpesviral biology and the regulation of mRNA accumulation and turnover in our own cells.
 
Article
The problems that are discussed in this chapter are confined to viruses, and to be more exact, to the question of similarities and differences between the structure and properties of usual forms of nucleic acids in solution and that of nucleic acids inside viral particles. Such differences should exist, as the viral particle is a rather peculiar and highly specialized object designed for storage and transport of the genetic substance of viruses. The properties of nucleic acids in situ ought to be affected by the environment, which they have in viruses, by the special functions that they have to perform, by their close partnership with protein, and by a number of other intraviral factors of which very little is known. The bulk of the information dealt with in this chapter is obtained by the means of X-ray diffraction and electron microscopy, various combinations of optical methods, and chemical and physical modifications combined with some way of recording corresponding results. There are a number of theoretical and practical difficulties to be overcome, which are discussed in detail in this chapter. Determination of true absorption, values of objects that scatter light in the region where they absorb, is always a matter of difficulty when conformation of intraviral nucleic acid is studied by means of absorption, anisotropic absorption, or optical rotatory dispersion (ORD). The use of the extrapolation method is often objected to form a theoretical point of view. The more specific problem of obscurity of UV dichroism data and some others are considered in this chapter.
 
Article
The history of the study of the nucleic acids has in fact been a tragic-comedy of the application of drastic methods to materials that in many ways are less stable than most proteins and are also susceptible to attack by a large number of enzymes, many of which are extremely stable and most of which are widely distributed. This state of affairs has left its mark on most of the work on nucleic acids and, not least, on that which has been done on the nucleic acids of viruses. In the viruses, the number of genetic characteristics is obviously less than is to be found, for example, in the vertebrates, and so one might expect that there would be less tendency for the summation of the compositions of numbers of different nucleic acids to smooth out to give a mean composition that may differ but little from species to species. Thus, one may see that more is likely to be deduced from the study of the nucleic acids of viruses and simple microorganisms than from those of the vertebrates, and particularly from those of the former, because the viruses, from a structural point of view, would appear to have a complexity that is the minimum necessity for the maintenance of genetic continuity and self-reproduction. The viruses, especially the plant viruses, are also extremely good sources of relatively “native” nucleic acid because one of the major difficulties in preparing such material is the fact that the nucleic acids are found in tissues, in which large amounts of the various phosphatases are present and consequently, it is difficult to ensure that enzymic degradation does not take place. With many of the viruses, however, it is possible to remove all the sources of enzymes before liberating the nucleic acids, and in those plant viruses that can be purified in adequate amounts, one has a source of ribonucleic acid of a quality that is unrivaled.
 
Article
This chapter discusses the current progress and future aspects of plant protoplast electrotransfection with viral nucleic acids, including several experimental results. Several factors—such as the biological condition of protoplast and viral nucleic acid samples, the capabilities of the apparatus, and the experimental conditions for transfection—affect the frequency of electrotransfection. The chapter describes the capabilities of the apparatus for electrotransfection. Under optimum conditions, almost all protoplasts are transfected with viral nucleic acid without remarkable protoplast damage. It seems possible that the optimum conditions for electrotransfection of one kind of plant protoplast are almost the same with any kind of viral nucleic acids isolated from virus particles. However, in conventional methods, using polycations, it is necessary to find the optimum conditions for the infection of protoplasts with different kinds of virus particles each time. Electrotransfection combined with in vitro mutagenesis is one of the most effective, simplest, and fastest methods for analyzing the relationships between the structure and the function of the genomes in the reverse genetics of plant viruses. Electrotransfection provides a simpler, more efficient, and more harmless method for the transfection of plant protoplasts with viral nucleic acids than the conventional method and it can be used for mass-scale experiments.
 
Article
Ionizing radiation may be employed to study the loss of infectivity of viruses and determine the size of the sensitive volume of the virus in consequence. Virus irradiation can be achieved by the bombardment technique. Fast electrons are being used for virus irradiation. Ionizing radiation inactivates a part of the virus. Ionizing radiation on water leads to the formation of H and OH radicals together with more durable products, such as H2O2 and HO2, in the presence of dissolved oxygen. These not only have an effect on the virus but also on any of the variety of molecules that could accordingly remove the “activation” of the water and so protect the virus. Indirect effects of radiation on T2 phage are described in the chapter. Experimental studies with T2 phage showed that two types of viral inactivation are present, one that is transient in time and requires irradiation of the virus and solution medium together, and other is an aftereffect that can be produced by adding virus to previously irradiated medium. The most striking action of ionizing radiation was on adsorption. The finding is very reasonable because irradiated water should act predominantly on the surface, which must also act in adsorption. Ionizing radiation also leads to an effect that developed with time after irradiation, and is presumably because of the products of radiation action that have long life. Damage produced in this way was strongly temperature-dependent and is apparently also of the cumulative damage type.
 
Article
This chapter emphasizes additional aspects of the part played by the interferons (IFNs) in determining the outcome of encounters between viruses and host cells. Specifically, it reviews the biosynthesis of IFNs with particular stress on molecular mechanisms by which the IFN-α/β genes are activated transcriptionally by virus infection. The induction of IFN-γ by immune activation of lymphocytes is also discussed. Subsequently, the means by which IFN stimulates nuclear transcription of specific genes are examined. The chapter reviews the IFN-induced proteins that possess documented roles in antiviral mechanisms, primarily to highlight recent observations. It also describes the strategies employed by viruses to confound the IFN-induced antiviral activities. The major conclusion of this chapter is that there is a prominent and instructive overlap between mechanisms of regulation of the interferon-stimulated genes (ISG) and the IFN-α/β genes themselves. This network of interacting gene-regulator influences has become more salient as some pathways of gene induction by IFNs have been elucidated.
 
Article
Successful transmission of murine leukemia by the passage of cell-free filtrates from leukemic tissue was first described in 1951. Viruses have subsequently been shown to be causally related to a wide variety of leukemias and lymphomas in many different mammalian species. Many of these viral agents were initially derived from tumors other than leukemias and some of them induce neoplasias uncharacteristic of those generally seen in nature. Others, however, were recovered initially from spontaneous or induced leukemias and induce similar tumors in the recipients. Still a third group of viruses were derived from apparently the normal tissues and were found to be capable of inducing leukemias or lymphomas either in the same or in a different genus or species of mammal. In these instances, the viral genetic information may vary from being unexpressed, partially or fully expressed. When viral information initially present in covert form becomes expressed in overt form, the process can be described as virus activation or induction. Many events, both physiological and pharmacological, are associated with the activation of leukemia viruses in vivo and in vitro. Among these events are radiation, treatment with hormones or chemicals, certain specific immunological reactions, and sometimes even aging itself. This chapter covers in vivo and in vitro activation of endogcnous mammalian leukemia viruses, both descriptively and analytically. It attempts to relate the phenomena described both to the current theories of viral oncogenesis and to the pathogenesis of mammalian cancer.
 
Article
This chapter discusses the features and characteristics of the E1A trans-activation system besides the related details deriving from other relevant viral systems. The studies of herpes virus trans-activation have provided many details both unique and similar to the E1A system. Each of the DNA viruses that replicates in the nucleus of virus infected cells—as well as many of the retroviruses—encodes a trans-activation function. SV40 T antigen, papillomavirus E2 and E7 gene products, hepatitis B virus pX protein, HIV tat gene product, and HTLV I and II tat gene products function to trans-activate transcription of the respective viral genomes. The characteristics of these systems have also been described in the chapter. Given a process of control through the activation of cellular transcription factors as well as evidence that in some cases, this results in the stimulation of specific cellular genes, a role for these proteins in altering cell proliferation control can be imagined.
 
Article
The hepatitis C virus (HCV) is a global public health problem affecting approximately 2% of the human population. The majority of HCV infections (more than 70%) result in life-long persistence of the virus that substantially increases the risk of serious liver diseases, including cirrhosis and hepatocellular carcinoma. The remainder (less than 30%) resolves spontaneously, often resulting in long-lived protection from persistence upon reexposure to the virus. To persist, the virus must replicate and this requires effective evasion of adaptive immune responses. In this review, the role of humoral and cellular immunity in preventing HCV persistence, and the mechanisms used by the virus to subvert protective host responses, are considered.
 
Article
The adeno-associated viruses (AAV) are defective parvoviruses that require coinfection with an adenovirus for a productive infection. In many ways AAV is a unique virus because of its special properties of dependence on adenovirus for replication and the fact that both plus and minus strands are encapsidated. It is a parvovirus but differs from the autonomous parvoviruses in its defectiveness, the encapsidation of both DNA strands, and the existence of an inverted terminal nucleotide sequence repetition in its genome. The ability of AAV to inhibit adenovirus DNA replication may indicate a common feature in an early step of DNA replication in spite of the apparent overall differences in the mechanism of initiation. The ability of various adenovirus variants to help AAV DNA replication may be used to screen for new genes involved in adenovirus DNA replication. AAV may inhibit SV40 DNA replication but is not helped by SV40 coinfection at the level of DNA. AAV inhibition of adenovirus and herpes simplex virus oncogenicity is another interesting phenomenon. There are no data concerning the level at which the interference takes place. The only suggestive data in this regard come from the observation that AAV does not have an effect on adenovirus oncogenicity in newborn Syrian hamsters. AAV can establish a latent infection in the normal host in the absence of concomitant adenovirus infection.
 
Article
The adeno-associated viruses (AAV) are the only known DNA animal viruses that are absolutely dependent upon coinfection by a second unrelated virus to undergo productive infection. They are members of the family Parvoviridae, which are among the smallest of the DNA animal viruses. The Parvoviridae genome is a linear single-stranded DNA molecule approximately 5 kb in size, which is encapsidated in a naked icosahedral particle 18–27 nm in diameter. In addition to one genus of insect viruses (densoviruses), the family contains two genera that infect a broad spectrum of vertebrates ranging from birds to humans. The parvoviruses are able to replicate autonomously in infected cells but require actively dividing cells for a productive infection. Although the dependoviruses (AAV) are structurally similar to the autonomous parvoviruses, they are absolutely defective and require coinfection with structurally unrelated adenoviruses or herpesviruses for a productive infection to occur. Adeno-associated virus does not have any structural relatedness to either of its helpers; on the other hand, the three viruses do represent all of the known vertebrate virus families with linear DNA genomes that replicate in cell nuclei.
 
Article
This chapter focuses on adeno-associated virus vector-mediated gene transfer to somatic cells in the central nervous system (CNS). The recombinant adeno-associated virus (rAAV) vector system incorporates features that make it a good choice for in vivo research. These features include efficient and long-term gene expression in a broad range of organs that appears to be well tolerated by laboratory animals. The brain is a, particularly good target for viral vector approaches because of the topic maps of neuroanatomical organization. Wild-type AAV infection commonly occurs early in life, and up to 80% of the human population is seropositive for AAV. AAV is a dependovirus requiring a helper virus to complete its life cycle. Apart from gene therapy applications, in vivo rAAV somatic cell gene transfer is likely to be useful for disease modeling. The pathology of Parkinson's disease is characterized by movement disorders concomitant with the degeneration of dopaminergic neurons in the substantia nigra and their axons in the striatum. Alzheimer's disease is, in part, a cholinergic deficit supported by the role of the neurotransmitter acetylcholine in memory function.
 
Article
This chapter emphasizes the current picture of the regulation of adenoviral gene expression. The large body of work discussed in this chapter amply documents the complexity and intricacy of the regulation of adenoviral mRNA production. The most obvious generalization that can be made concerns the relative roles of transcriptional and posttranscriptional regulation. It seems obvious that transcriptional control must determine when during the productive cycle a particular transcription unit is expressed. However, transcription units that are transcribed in adenovirus-infected cells do not necessarily generate functional mRNA species, a situation exemplified by many cellular transcription units during the late phase of infection. Moreover, a subtle network of posttranscriptional regulatory circuits is superimposed upon transcriptional control mechanisms. These can determine both the nature of the end product generated from a given transcript and the relative concentrations of individual mRNA species that may be processed from that transcript. Thus, the fine tuning of regulation of adenoviral gene expression appears to be largely a posttranscriptional affair.
 
Article
This chapter discusses the structure and biology of adenovirus (Ad) and its exploitation to create a high-level expression vector with use in human gene therapy as one of its most exciting applications. Some of the problems associated with Ad gene therapy, including the host-immune response to Ad, and some potential solutions to these problems are also discussed. The ability of Ad to transduce a wide variety of cell types with high efficiency and the relative ease with which the viral genome can be manipulated genetically make it an ideal vehicle for gene therapy. One of the most promising advancements in Ad gene therapy is the development of helper-dependent Ad vectors, which have maximal cloning capacity, because all of the viral genes have been removed and would be expected to induce a minimal host-immune response. Other recent innovations in vector design described in the chapter include the generation of hybrid Ad vectors to facilitate the transgene integration and manipulations of Ad vectors for targeting specific cell types. First-generation vectors are in many cases, the most effective means at hand for in vivo delivery of foreign genes, and they have proven useful as research tools for efficient gene delivery and expression in vitro.
 
Article
Publisher Summary This chapter discusses recent results concerning early and late adenovirus messenger RNAs and proteins. An emphasis on their map positions on the viral genome and their possible function in early and late virus gene expression is considered appropriate. An attempt to review available data on adenovirus assembly is also included. The chapter focuses on gene expression of the group C human adenoviruses comprising the thoroughly studied types ad2 and ad5. Similar, but not identical, results have been reported for other human and avian adenoviruses but in most cases, the human group C adenoviruses have been studied in more detail at the molecular level. The chapter concludes that delineation of the molecular events occurring at both the initiation of DNA replication and transcription in a mammalian cell will be forthcoming.
 
Article
The mechanism, as well as the regulation, of the biogenesis of adenovirus messenger RNA (mRNA) has been the subject of intensive research over the past several years, principally because it provides an excellent model for the events that occur in the uninfected mammalian cell. The usefulness of adenovirus as a model system is illustrated in this chapter. Adenovirus is a double-stranded DNA virus, which replicates in the nucleus of infected cells. The virus carries no known enzymes into the cell and thus, is completely dependent upon the cellular machinery for at least the initial transcription of its genome. Purified adenovirus DNA can be prepared in large quantities so that defined segments of the genome are available in sufficient amounts for most experiments. The chapter presents a more limited picture of the processes involved in the production of a group of specific mRNAs. As the most comprehensive information available is that dealing with the production of the late adenovirus mRNAs, it is the subject on which the chapter focuses, making reference when appropriate to other systems.
 
Article
The life of adenoviruses began with the investigations of the structure of the virion and the mechanism of its replication. Purification of the virus and electron microscopic examination revealed the virion to be a highly structured icosahedron with a fiber protein at each apex. It was then found that adenoviruses contain DNA and the virion was attached to susceptible cells via the fibers. Hexon, the major capsid protein, not the fiber attachment protein, contains the antigen that stimulates the development of virus-specific, neutralizing antibodies. This is essential to state because many virologists believe that neutralizing antibodies merely inhibit virion attachment to susceptible cells. The influenza virus neutralizing antibody-stimulating antigen does not prevent attachment to susceptible cells, although this critical antigen is on the stem of the hemagglutinin structure. The chapter discusses about the researcher who had done extensive work in the study of adenovirus.
 
Article
The Tetraviridae are a family of insect viruses with small, isometric particles, and single-stranded positive-sense RNA (ss +RNA) genomes that have received relatively little attention from virologists. Their obscurity is due mainly to their perceived lack of economic importance and the difficulty of their study, but recently the situation changed. This chapter discusses the significance of tetraviridae viruses to diverse fields of study and describes their newfound economic potential. The reports of complete genome sequences of tetraviruses from both groups and the determination of the crystal structure of an ω-like virus. These and other data that are rapidly emerging about their pathology and replication strategies appear to have broad implications for areas as diverse as cell and structural biology, virus evolution, and agricultural and medical biotechnology. The high resolution tetravirus structure has given fundamental insights into the structure and function of viral structural proteins. The identification of the capsid protein surface domain—implicated in cell binding—represents the first such observation on a simple, nonenveloped, icosahedral virus.
 
Article
Tick-borne encephalitis (TBE), one of the most dangerous neuroinfections in Europe and Asia, is caused by tick-borne encephalitis virus (TBEV) and currently involves approximately 11,000 human cases annually, mostly in Russia. This chapter describes the main problems associated with the epidemiology, ecology, pathogenesis, and control of this disease. We have attempted to review the factors that influence the incidence and distribution of TBE, and to discuss possible reasons for the different clinical manifestations including most commonly observed asymptomatic infections, fever forms, acute encephalitis, and the less frequently registered biphasic milk fever and chronic encephalitis. Epidemiologic data concerning the other tick-borne flaviviruses, namely Louping ill virus, Langat virus, and Powassan virus that also produce encephalitis on a smaller scale, are also presented. Here we describe the history and current epidemiological role of Omsk hemorrhagic fever virus and Kyasanur forest disease virus, two viruses that are genetically closely related to TBEV, but produce hemorrhagic fever instead of encephalitis, and provide possible explanations for these differences. The other viruses in the tick-borne flavivirus group are also included despite the fact that they do not play an essential epidemiologic role in humans. This chapter contains a brief history of vaccination against TBE including the trials with live attenuated vaccine and reviews the modern trends in development of vaccine virus strains.
 
Geographical distribution of bat lyssavirus isolates across the globe. Countries are shaded according to the detection of different lyssavirus species in bats. Where only single isolates have been detected, viruses are denoted by symbols. Lyssavirus species are colored according to the key.
Phylogenetic analysis of characterized lyssavirus isolates based on 405 nucleotides of the nucleoprotein. Sequences were aligned using the ClustalW, and the tree was visualized using Treeview (Version 3.2). Bootstrap values at significant nodes are shown. For each lyssavirus species, animals found naturally infected are silhouetted at branch termini. Differentiation into phylogroups according to antigenicity is labeled and separated by dashed lines. 
Geographical distribution of both bat-associated lyssavirus isolates and detection of WCBV neutralising antibodies across Africa. Isolates are colored as shown in the key.
Colonies of E. helvum roosting in trees in Accra, Ghana. Images courtesy of David Hayman.
Maximum likelihood phylogenetic tree of 36 partial N gene sequences (590 nucleotides) of RABV isolated from at least 27 different bat species from across the Americas. Previously identified bat RABV lineages are shown (Nadin-Davis et al., 2001). Significant bootstrap values (> 70%, 1000 replicates) are indicated. Latin names of bats are detailed in black boxes (white text) with sample identification codes corresponding to Table IV. 
Article
Numerous bat species have been identified as important reservoirs of zoonotic viral pathogens. Rabies and rabies-related viruses constitute one of the most important viral zoonoses and pose a significant threat to public health across the globe. Whereas rabies virus (RABV) appears to be restricted to bats of the New World, related lyssavirus species have not been detected in the Americas and have only been detected in bat populations across Africa, Eurasia, and Australia. Currently, 11 distinct species of lyssavirus have been identified, 10 of which have been isolated from bat species and all of which appear to be able to cause encephalitis consistent with that seen with RABV infection of humans. In contrast, whereas lyssaviruses are apparently able to cause clinical disease in bats, it appears that these lyssaviruses may also be able to circulate within bat populations in the absence of clinical disease. This feature of these highly encephalitic viruses, alongside many other aspects of lyssavirus infection in bats, is poorly understood. Here, we review what is known of the complex relationship between bats and lyssaviruses, detailing both natural and experimental infections of these viruses in both chiropteran and nonchiropteran models. We also discuss potential mechanisms of virus excretion, transmission both to conspecifics and spill-over of virus into nonvolant species, and mechanisms of maintenance within bat populations. Importantly, we review the significance of neutralizing antibodies reported within bat populations and discuss the potential mechanisms by which highly neurovirulent viruses such as the lyssaviruses are able to infect bat species in the absence of clinical disease.
 
Article
This chapter focuses on the advances in iridovirus research over the past decade. It summarizes salient features of the iridovirus research studies, and discusses their importance to future work. As knowledge of iridovirus biology increases, so does the understanding of the taxonomic structure of the family. A new genus (Megalocytivirus) has recently been created to accommodate a number of viruses isolated from diseased fish in Southeast Asia, and an established one (Chloriridovirus) is about to be validated following the sequencing of the genome of the mosquito pathogen IIV-3. Genomic sequencing projects have clarified evolutionary relationships between iridoviruses and other families of large, nucleocytoplasmic DNA viruses. Iridoviruses appear situated at the center of a clade of DNA viruses that include the poxviruses, phycodnaviruses,ASFV, ascoviruses, and possibly a new giant virus of amoebae (mimivirus). Not all iridovirus infections result in mortal disease. The recognition that many iridovirus infections are chronic, especially among insects, should stimulate studies on the importance of such illnesses on host fitness. Sublethal effects have been demonstrated in infected insects, and theoretical studies suggest such effects have a major influence on the dynamics of host populations. However, the consequences of chronic disease on the demography (fecundity, fertility, death rate, etc.) of infected amphibian and fish populations are notable by their absence. The ability to detect iridovirus infections has advanced markedly with the adoption of highly sensitive loop-mediated isothermal amplification and multiplex polymerase chain reaction techniques for rapid diagnosis of infected individuals.
 
Article
The regular increase of drug-resistant pathogens has been a major force in the renewed interest in the use of bacteriophages as therapeutics. In addition to experience acquired in eastern Europe where bacteriophages have been used to treat bacterial infections in humans, in Western countries only experimental models have been developed until recently. The Gram-negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen causing particularly severe infections in cystic fibrosis patients. Several experimental models in mice have yielded encouraging results for the use of bacteriophages to treat or prevent septicemia, skin and lungs infections caused by P. aeruginosa. Now, a phase II clinical trial conducted in the United Kingdom provides evidence for the efficacy of bacteriophage treatments in chronic otitis due to antibiotic-resistant P. aeruginosa strains. Together with experimental models, these results provide an incentive to develop more research and clinical studies to fully appreciate the benefits of the use of bacteriophages in medicine.
 
Article
Bacteria Pseudomonas aeruginosa, being opportunistic pathogens, are the major cause of nosocomial infections and, in some cases, the primary cause of death. They are virtually untreatable with currently known antibiotics. Phage therapy is considered as one of the possible approaches to the treatment of P. aeruginosa infections. Difficulties in the implementation of phage therapy in medical practice are related, for example, to the insufficient number and diversity of virulent phages that are active against P. aeruginosa. Results of interaction of therapeutic phages with bacteria in different conditions and environments are studied insufficiently. A little is known about possible interactions of therapeutic phages with resident prophages and plasmids in clinical strains in the foci of infections. This chapter highlights the different approaches to solving these problems and possible ways to expand the diversity of therapeutic P. aeruginosa phages and organizational arrangements (as banks of phages) to ensure long-term use of phages in the treatment of P. aeruginosa infections.
 
Genome organization of PepMV and ToTV. (A) The PepMV genome comprises a single, positive-sense, $6400-nt RNA strand containing five open reading frames encoding the putative viral polymerase (RdRp), the triple gene block proteins (TGBp1, TGBp2, and TGBp3), the coat protein (CP), and two short untranslated regions (UTRs) flanking the coding regions; there is a poly(A) tail at the 3 0 end of the genomic RNA. Genes are expressed from genomic and subgenomic RNAs. (B) The ToTV genome is divided into two positive-sense RNA molecules of about 7800 bp (RNA1) and 5400 bp (RNA2). RNA1 contains one open reading frame encoding a polyprotein with motifs representing RNA-dependent RNA polymerase (RdRp), protease cofactor (Pro-Co), and helicase (He). RNA2 contains two open reading frames encoding the putative movement protein (MP) and three coat proteins (CPs). Two UTRs flank the coding regions with a poly (A) tail at the 3 0 end of the genomic RNAs 1 and 2.
Phylogenetic tree for the full-length genome sequence of seven PepMV isolates. The tree was built using the neighbor-joining method with 1000 bootstrap replicates in MEGA 4. LE2000 and Sp13 are Spanish isolates (accession numbers AJ600359 and NC004067, respectively), LP2000 is a Peruvian isolate (accession number AJ606361), US1 is an american isolate (accession number AY509926), CH2 is a Chilean isolate (accession number DQ000985) and Pa and PK are Polish isolates (accession numbers FJ612601 and EF408821, respectively)
Detection of PepMV in samples from symptomatic tomato plants. Detection of PepMV-EU and/or PepMV-CH2 in infected samples of commercial tomato crops in the Murcia region over a period of 8 years. Data from 2000 to 2004 are from Pagan et al. (2006).
Effective number of PepMV infections. Bayesian skyline plot (m ¼ 10) showing the evolution of the effective number of PepMV infections. N e t represents the effective number population size times the generation time (in years). The thick line is the median estimate, and the dashed gray lines show the 95% HPD limits. The plot shows a sharp increase in the effective number of infections around 2005 (Gómez et al., 2012).
Article
The molecular biology, epidemiology, and evolutionary dynamics of Pepino mosaic virus (PepMV) are much better understood than those of Tomato torrado virus (ToTV). The earliest descriptions of PepMV suggest a recent jump from nontomato species (e.g., pepino; Solanum muricatum) to tomato (Solanum lycopersicum). Its stability in contaminated plant tissues, its transmission through seeds, and the global trade of tomato seeds and fruits may have facilitated the global spread of PepMV. Stability and seed transmission also probably account for the devastating epidemics caused by already-established PepMV strains, although additional contributing factors may include the efficient transmission of PepMV by contact and the often-inconspicuous symptoms in vegetative tomato tissues. The genetic variability of PepMV is likely to have promoted the first phase of emergence (i.e., the species jump) and it continues to play an important role as the virus becomes more pervasive, progressing from regional outbreaks to pandemics. In contrast, the long-term progression of ToTV outbreaks is not yet clear and this may reflect factors such as the limited accumulation of the virus in infected plants, which has been shown to be approximately two orders of magnitude less than PepMV. The efficient dispersion of ToTV may therefore depend on dense populations of its principal vectors, Bemisia tabaci and Trialeurodes vaporariorum, as has been proposed for the necrogenic satellite RNA of Cucumber mosaic virus.
 
Article
Publisher Summary This chapter describes various methods that are used to measure absolute and relative affinities, to pinpoint the difficulties and errors inherent in some of them, and to attempt to rationalize their solution. The heterogeneous nature of antibodies in antisera makes meaningful measurements of affinity very difficult. Different values of association constant and viral valency can be generated for a single antiserum from experiments carried out at different antibody dilutions, and particular antibody valencies cannot be assumed. Nevertheless, the Scatchard form of analysis can yield useful information about the range of affinities within an antibody population and under appropriate conditions can produce accurate estimates of virus valency. Solid-phase measurements have considerably simplified the mechanical operations of antibody/antigen assays. They can, however, be subject to errors because of limiting diffusion rates at low antibody concentration, conformational distortion of coated antigen, artificial increases of avidity at high coating concentrations, and differential binding of secondary label. Comparative assays can provide useful estimates of relative affinities if they are used in the sensitive range for any particular antibody-antigen assay system. Solid-phase coating densities critically affect the sensitivities of these assays to relative affinities. Monoclonal antibodies pose particular problems because of their individual characteristics in terms of affinity, behavior in different physical and chemical environments, and detectability with secondary label. These factors affect the suitability of different types of assay for detection of relative affinities.
 
Estimated extent of the epidemic of the CMD pandemic in SSA in years 1997, 2001 and 2005. DR Congo, Democratic Republic of Congo; R Congo, Republic of Congo; Rw., Rwanda; Bu., Burundi.  
Epidemic index values for cassava mosaic disease in regions of SSA surveyed between 1998 and 2003.  
Risk assessment map for the CMD pandemic in East/Central Africa, 2001.  
(A) Vegetation map for Central/West Africa used to predict spread of EACMV-UG into Gabon ( Anon, 2005d). (B) Occurrence and distribution of cassava mosaic geminiviruses in Gabon, 2003 (Legg et al. , 2004).  
CMD incidence and abundance of B. tabaci whiteflies recorded from initially CMD-free plots of the local CMD-susceptible cultivar 'Bao' planted at Namulonge, Uganda from 1992–99 (CMD incidence was the percentage of plants infected with CMD at the end of each trial, 12 months after planting; whitefly abundance was the mean number of B. tabaci adults on the top five leaves of a representative shoot of plants sampled weekly over a period of 6 months from 2–8 months after planting).  
Article
This chapter provides a detailed description of the character, pattern of spread and impact of the pandemic and reviews management initiatives implemented to mitigate against its effects. It assesses the status of the pandemic and recommendations for its improved management. Although cassava mosaic disease (CMD) has been an important constraint to cassava production in Africa for more than a century, changes in the nature of the disease during the last two decades have led to losses on a hitherto unprecedented scale. Strategic epidemiological studies that have traced the development and spread of what is now known as the African CMD pandemic have provided vital insights into the mechanisms and pattern through which this disease is spread and the critical interactions with its whitefly vector, B. tabaci. Based on this new knowledge, an effective and wide-ranging management programme has been implemented utilizing each of the principal virus management tools, although the primary focus has been on the deployment of host-plant resistance. There has been a substantial impact in areas where management programmes have run for several years. The best example of this is Uganda, where more than a third of the cassava crop is under CMD-resistant varieties.
 
Article
Of the seven compounds currently approved by the U.S. Food and Drug Administration (FDA) as antiviral agents for use in humans, six are nucleoside or nucleotide analogs. Amantadine (l-adamantanamine hydrochloride), the first antiviral compound to be licensed for clinical use, is the sole exception. Effective in the prophylaxis and therapy of influenza A infections, amantadine appears to inhibit the initiation of transcription at an early stage between uncoating and virus-specific RNA synthesis. Idoxyuridine (IDU, 5-iodo-2 ‘-deoxyuridine) represents the first antiviral drug to be successfully used for preventing development of severe ocular lesions and blindness because of herpesvirus infections. Its activity is limited to DNA viruses, specifically herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and varicella zoster virus (VZV). Being poorly soluble in water, aqueous solutions of IDU are ineffective against infections other than those localized in the eye. Trifluorothymidine (TFT, 5-trifluoromethyl-2’-deoxyuridine) is another halogenated pyrimidine nucleoside analog licensed for use in humans.
 
Article
The target protein (enzyme) with which antiviral agents interact determines their antiviral activity spectrum. Based on their activity spectrum, antiviral compounds could be divided into the following classes: (1) sulfated polysaccharides (i.e., dextran sulfate), which interact with the viral envelope glycoproteins and are inhibitory to a broad variety of enveloped viruses (i.e., retro-, herpes-, rhabdo-, and arenaviruses): (2) SAH hydrolase inhibitors (i.e., neplanocin A derivatives), which are particularly effective against poxvirus, (-)RNA viruses (paramyxovirus, rhabdovirus), and (+/-)RNA virus (reovirus); (3) OMP decarboxylase inhibitors (i.e., pyrazofurin) and CTP synthetase inhibitors (i.e., cyclopentenylcytosine), which are active against a broad range of DNA, (+)RNA, (-)RNA, and (+/-)RNA viruses; (4) IMP dehydrogenase inhibitors (i.e., ribavirin), which are also active against various (+)RNA and (-)RNA viruses and, in particular, ortho- and paramyxoviruses; (5) acyclic guanosine analogs (i.e., ganciclovir) and carbocyclic guanosine analogs (i.e., cyclobut-G), which are particularly active against herpesviruses (i.e., HSV-1, HSV-2, VZV, CMV); (6) thymidine analogs (i.e., BVDU, BVaraU), which are specifically active against HSV-1 and VZV because of their preferential phosphorylation by the virus-encoded thymidine kinase; (7) acyclic nucleoside phosphonates (i.e., HPMPA, HPMPC, PMEA, FPMPA), which, depending on the structure of the acyclic side chain, span an activity spectrum from DNA viruses (papova-, adeno-, herpes-, hepadna-, and poxvirus) to retroviruses (HIV); (8) dideoxynucleoside analogs (i.e., AZT, DDC), which act as chain terminators in the reverse transcriptase reaction and thus block the replication of retroviruses as well as hepadnaviruses; and (9) the TIBO, HEPT, and other TIBO-like compounds, which interact specifically with the reverse transcriptase of HIV-1 and thus block the replication of HIV-1, but not of HIV-2 or any other retrovirus.
 
Article
The discovery of the “Australia antigen” as a marker of hepatitis B infection, and the visualization of the 27-nm hepatitis A viral particle made it possible to develop reliable diagnostic assays for the detection of hepatitis A virus (HAV) and hepatitis B virus (HBV). Nevertheless, the appearance of post-transfusion associated hepatitis in patients negative for markers of either virus led researchers to believe that another new agent(s) existed. Such an agent(s) came to be known as non-A, non-B hepatitis (NANBH). In the past two years, major discoveries in the area of viral hepatitis have led to the identification of two new agents: hepatitis C virus (HCV), which is believed to cause the majority (at least 90%) of parenterally transmitted non-A, non-B hepatitis (PT-NANBH), and hepatitis E virus (HEW), responsible for enterically transmitted non-A, non-B hepatitis (ET-NANBH). This brings the number of known hepatotropic agents to five— namely, hepatitis A, B, C, D, and E viruses. HAV and HEV are spread by the fecal/oral route, whereas HBV, HCV, and HDV are transmitted principally by parenteral routes (e.g., blood and blood-derived products). These viral agents, with the exception of HBV, have RNA genomes. The successful development and application of molecular cloning strategies that had previously been applied to the elucidation of rare or low-abundance genes and gene transcripts have hastened the cloning and characterization of low-titer viruses that have not yet been successfully propagated in vitro. This chapter reviews the developments of the past two years that led to the successful identification of HCV and HEV.
 
Article
In plant virology, viruses are mostly dealt with as useful molecular biological tools in studies of the riddle of life. However, viruses were first detected and studied as incitants of disease, and those which damage crops, continue to cause considerable concern to society as major constraints in agricultural production. The pressure for agricultural development is especially high in the developing countries, most of which are located in the tropics, where agricultural productivity lags behind rapid population increases. Traditional subsistence agriculture on small-scale holdings, with a great variety of crops often grown in mixtures, is rapidly giving way to modern agricultural practices, with genetically more homogeneous monocultures grown over large acreages. The ensuing trade and transport of produce via complex peripheral organizations further allow and stimulate personal and regional specialization in agricultural production, in turn, leading to further change. Economically, such modernization is usually interpreted in terms of usefulness. But with increasing awareness of the complexity of nature and of agroecosystems, man is becoming increasingly alert that every coin has another side and that human interference is ambivalent. Through agricultural modernization, present day crops are often more vulnerable to a wide range of pests that, according to the Food and Agricultural Organization (FAO) definition, include weeds and viruses. Most, if not all, crop diseases and pests are man-made and new problems arise as a corollary of agricultural modernization. These problems are discussed in this chapter, with special reference to viruses, which play an intricate, intriguing, and often incompletely understood role that has a high impact on human society. This chapter concentrates on the developing countries, and thus largely on the tropics, because agricultural progress is hoped to be especially rapid there and also because of the author's involvement in the activities of organizations, such as the FAO, the International Board for Plant Genetic Resources (IBPGR), and International Agricultural Research Centres (IARCs) of the Consultative Group on International Agricultural Research (CGIAR) that are committed to helping to increase crop productivity in developing parts of the world in order to alleviate food shortages and improve the living standards.
 
Article
The incurable nature of viral diseases and the public awareness to the harmful effects of chemical pest control to the environment and human health led to the rise of the integrated pest management (IPM) concept. Cultural control methods serve today as a central pivot in the implementation of IPM. This group of methods is based on the understanding of the complex interactions between disease agents and their vectors as well as the interactions between the vectors and their habitat. This chapter describes a set of cultural control methods that are based on solar light manipulation in a way that interferes with vision behavior of insects, resulting in a significant crop protection against insect pests and their vectored viruses.
 
Models for HIV-1 infection of the brain. Trojan horse: diapedesis of HIVinfected cell through the MVEC monolayer and subsequent brain infection. Transcytosis: direct passage of HIV through MVEC monolayer by adsorption and subsequent budding to ablumenal side. Direct infection of MVEC: chemoattraction and adhesion of uninfected monocytes to HIV-infected, adhesion molecule-expressing MVECs with subsequent diapedesis of monocyte through MVEC monolayer. Infection of monocytes would result from passage through the infected MVEC monolayer, and spread of virus into the brain parenchyma would result from the now perivascular, HIV-infected monocytes. Blood-brain barrier disruption: any or all of the models proposed may result in a transient disruption of tight junctions, allowing free virus, virus-infected cells, and neurotoxic molecules access to the brain parenchyma.
[For color reproduction, see the color section.] HIV productively infects brain M V E C in vitro. Positive indirect immunofluorescence for viral p24 in HIV-infected MVEC. 
Model for the generation of MVEC-tropic HIV within infected bone marrow. HIV infects bone marrow early during the disease course, resulting in the derivation of MVECtropic strains that then preferentially seed into brain by penetrating the BBB. 
Article
This chapter focuses on how human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) are proposed to interact with and cross the blood–brain barrier (BBB) and to effect central nervous system (CNS) damage. The CNS as a reservoir of virus and the BBB as a limitation to the eradication of HIV are discussed. Animal and tissue culture models for the study of virus interactions with the BBB are reviewed. HIV infection of the CNS is currently one of the most challenging aspects of HIV-induced disease, despite the recent relative success of highly active antiretroviral therapy. Although HIV-induced pathological changes in the brain have been well documented in the absence of opportunistic infections, the mechanisms of viral entry into the brain are little understood as are the sequelae following virus entry. While HIV has now been clearly shown to infect the CNS, neural elements, including neurons and oligodendrocytes, surprisingly do not appear to be directly infected by virus. The BBB is an anatomical barrier between the general circulation and the brain parenchyma. The BBB is composed of specialized microvascular endothelial cells (MVECs) in contact with astrocytes. The contact between brain MVECs and astrocyte foot processes has been postulated to be critical for the formation of the barrier. Some of the enabling properties of the BBB are limited pinocytotic vesicular transport, the presence of tight junctions among endothelial cells, and a selective permeability to physiological ions.
 
Top-cited authors
Marilyn Roossinck
  • Pennsylvania State University
Victor Max Corman
  • Charité Universitätsmedizin Berlin
Ernest Gould
  • Aix-Marseille Université
Ari Helenius
  • ETH Zurich
Mark Marsh
  • University College London