Mechanisms of cell entry by influenza virus
ABSTRACT A wide range of viruses, including many human and animal pathogens representing various taxonomic groups, contain genomes that are enclosed in lipid envelopes. These envelopes are generally acquired in the final stages of assembly, as viruses bud from regions of the membrane of the infected cell at which virally encoded membrane proteins have accumulated. The viruses procure their membranes during this process and mature particles 'pinch off' from the cellular membranes. Under most circumstances, initiation of another round of infection is dependent on two critical functions supplied by the envelope proteins. The virus must bind to cell-surface receptors of a new host cell, and fusion of the viral and cellular membranes must occur to transfer the viral genome into the cell. Enveloped viruses have evolved a variety of mechanisms to execute these two basic functions. Owing to their relative simplicity, studies of binding and fusion using enveloped viruses and their components have contributed significantly to the overall understanding of receptor-ligand interactions and membrane fusion processes - fundamental activities involved in a plethora of biological functions.
- SourceAvailable from: PubMed Central
[Show abstract] [Hide abstract]
- "HA is responsible for membrane fusion of the viral envelope with the host cell membrane . However, HA does not induce membrane fusion in neutral conditions, and it acquires its fusion activity through conformational change in acidic conditions [45, 46]. Viral particles are taken into the endosomes of host cells by endocytosis after HN-receptor binding, thereby exposing the particles to acidic conditions. "
ABSTRACT: A virosome is an artificial envelope that includes viral surface proteins and lacks the ability to produce progeny virus. Virosomes are able to introduce an encapsulated macromolecule into the cytoplasm of cells using their viral envelope fusion ability. Moreover, virus-derived factors have an adjuvant effect for immune stimulation. Therefore, many virosomes have been utilized as drug delivery vectors and adjuvants for cancer therapy. This paper introduces the application of virosomes for cancer treatment. In Particular, we focus on virosomes derived from the influenza and Sendai viruses which have been widely used for cancer therapy. Influenza virosomes have been mainly applied as drug delivery vectors and adjuvants. By contrast, the Sendai virosomes have been mainly applied as anticancer immune activators and apoptosis inducers.12/2013; 2013(5038):764706. DOI:10.1155/2013/764706
[Show abstract] [Hide abstract]
- "After endocytic uptake of the influenza virus into the host cell, the viral genome segments must be released into the cytoplasm and transported to the nucleus to initiate RNA transcription and replication (Cross et al., 2001a). This endosomal escape of the virus critically depends on the activity of two viral proteins which are both activated at the low endosomal pH: the M2 proton channel, required for uncoating of the viral ribonucleoproteins, and the HA protein, which upon acidification adopts a fusogenic conformation to cause fusion of the endosomal and viral membranes and formation of a fusion pore (Cross et al., 2001a). Therefore, dually acting polycyclic amines which combine blockade of the M2 channel with an inhibitory effect on HA refolding, appear highly attractive . "
ABSTRACT: We here report on the synthesis of new series of polycyclic amines initially designed as ring-rearranged analogs of amantadine and featuring pentacyclo, hexacyclo, and octacyclo rings. A secondary amine, 3-azahexacyclo[126.96.36.199(1,5).0(5,12).0(6,10).0(11,15)]pentadeca-7,13-diene, 3, effectively inhibited A/M2 proton channel function, and, moreover, possessed dual activity against an A/H3N2 virus carrying a wild-type A/M2 proton channel, as well as an amantadine-resistant A/H1N1 virus. Among the polycyclic amines that did not inhibit influenza A/M2 proton channel function, several showed low-micromolar activity against tested A/H1N1 strains (in particular, the A/PR/8/34 strain), but not A/H3N2 influenza viruses. A/PR/8/34 mutants selected for resistance to these compounds possessed mutations in the viral hemagglutinin that markedly increased the hemolysis pH. Our data suggest that A/H1N1 viruses such as the A/PR/8/34 strain are particularly sensitive to a subtle increase in the endosomal pH, as caused by the polycyclic amine compounds.Antiviral research 06/2013; 99(3). DOI:10.1016/j.antiviral.2013.06.006 · 3.94 Impact Factor
[Show abstract] [Hide abstract]
- "After mutation in the amminoacids which form the cleavage site, some strains turn that site unstable allowing proteases to break it, thus favoring infection. This is the main pathogenicity acquisition mechanism of the influenza virus, which can be followed by mutations in other sites which could favor adsorption and viral penetration, in addition to increasing its pathogenicity (Cross et al., 2001). The nucleotide sequencing of all influenza genome virus has revealed that the 1957's Asian pandemic (the introduction of an A/H2N2 influenza virus), and the Hong Kong pandemics in 1968 (the introduction of an A/H3N2 influenza virus) were caused by an influenza virus resulting from an antigenic rearrangement (Scholtissek et al, 1978; Li et al., 2004). "
ABSTRACT: Among reemerging illnesses, influenza constitutes one of the main concerns. The avian influenza has recently demonstrated the strong transmission capacity of the etiological agent -a virus from the Orthomyxoviridae family - associated to high pathogenic manifestations of the illness. The strong mutation capacity of this virus, through different hosts, reveals how important integrated actions aiming at monitoring its presence in different species are. The swine infection represents an additional concern not only in relation to that species but also in relation to the possibility of the virus to mutate and adapt to humans. The elements that determine the pathogenicity of the various viral subtypes must be well understood, for the tools used to control the illness - such as vaccination - may promote viral mutation and thus render the control even more difficult instead of favoring it. The present review aims at characterizing various components involved in the virus maintenance in different species as well as the determinant elements involved in its evolution, from the point of view of Conservation Medicine, which is the branch of science that deals exactly with the interaction among the environment, human beings, and animals, thus creating a holistic vision not only of the problem but also of the coherent and effective actions involved in their solution.Brazilian Archives of Biology and Technology 07/2009; 52(4). DOI:10.1590/S1516-89132009000400010 · 0.55 Impact Factor