Murray B Gardner

Murray B Gardner
University of California, Davis | UCD · Center for Comparative Medicine

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316
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Publications (316)
Article
Background: For the past 30 years, Simian AIDS has provided an indispensible animal model for the human disease. This historical perspective highlights the circumstances leading to the creation of this experimental model. Methods: Historical information and stored non-human primate (NHP) specimens, including isolates of Simian immunodeficiency v...
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Our long-term goal is to discover the combination of host parameters that help some HIV-infected individuals to resist progression to AIDS. In this study, we examined antibody responses using multiple samples obtained from a cohort of Long-Term Non-Progressors (LTNPs). Our hypothesis is that antibody responses to variable regions of the HIV-1 envel...
Article
Various strains of mice were exposed to ambient or filtered Los Angeles air. Filters removed most pollutants except nitric oxide and carbon monoxide. Maximum levels during 1962--64 were: oxidants--< 0.5 ppM, NO/sub 2/--< 0.6 ppM, NO--1.2 ppM, CO--40 ppM, hydrocarbons--12 ppM, SO/sub 2/--0.02 ppM. Monthly averages were approximately an order of magn...
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The University of California, Davis hosted a symposium on innate immunity in January 2012. Professors Bruce Beutler, Jules Hoffmann, Luke O'Neill and Pamela Ronald discussed their research on mechanisms that multicellular organisms use to recognize microbes.
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Human papillomavirus (HPV) is associated with premalignant lesions such as high-grade cervical intraepithelial neoplasia (CIN-III) with potential progression to cervical carcinoma. There are now preventive vaccines against HPV. However, no effective therapeutic vaccine or immunological treatment exists for individuals already infected or for the 47...
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Immune responses against hepatitis C virus (HCV) have been studied by numerous groups. However, details concerning the production of antibodies to antigenically variable epitopes remain to be elucidated. Since the sequences of the variable regions of several HCV proteins are different among the virus strains infecting patients, we decided to design...
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Evaluation of: Hansen SG, Vieville C, Whizin N et al. Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge. Nat. Med. 15(3), 293–299 (2009). The quest for a HIV vaccine that prevents HIV infection remains an ongoing struggle after failures of candidate vaccines in cli...
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Macaques have served as models for more than 70 human infectious diseases of diverse etiologies, including a multitude of agents-bacteria, viruses, fungi, parasites, prions. The remarkable diversity of human infectious diseases that have been modeled in the macaque includes global, childhood, and tropical diseases as well as newly emergent, sexuall...
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Research on animal retrovirus infections has contributed mightily to our understanding of biology and disease over the past century. Until the 1980s most attention was directed at the cancer-inducing role of the oncogenic retroviruses and, in particular, their genetic transmission in inbred mice as endogenous proviral DNA. Only since the onset of t...
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Newborn rhesus macaques were infected with two chimeric simian-human immunodeficiency virus (SHIV) strains which contain unique human immunodeficiency virus type 1 (HIV-1) env genes and exhibit distinct phenotypes. Infection with either the CCR5-specific SHIVSF162P3 or the CXCR4-utilizing SHIVSF33A resulted in clinical manifestations consistent wit...
Article
The author has had the unique opportunity to participate, over the last 35 years, in the retrovirus research field that proceeded and followed the discovery of human, simian and feline AIDS. The onset of human AIDS was certainly unanticipated, but in retrospect, the warning signs had been present for at least a decade in captive macaques. I will br...
Chapter
Animal retroviruses are classified within seven different genera, of which members of five genera are present in primates C-type virus, D-type virus, human T-cell leukemia virus (HTLV), simian T-cell lymphotropic virus (STLV), bovine leukemia virus (BLV), lentiviruses, and spuma or foamy viruses. This chapter reviews the salient biology of each of...
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Attenuated molecular clones of simian immunodeficiency virus (SIVmac) are important tools for studying the correlates of protective immunity to lentivirus infection in nonhuman primates. The most highly attenuated SIVmac mutants fail to induce disease but also fail to induce immune responses capable of protecting macaques from challenge with pathog...
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Human cytomegalovirus (HCMV) possesses low pathogenic potential in an immunocompetent host. In the immunosuppressed host, however, a wide spectrum of infection outcomes, ranging from asymptomatic to life threatening, can follow either primary or nonprimary infection. The variability in the manifestations of HCMV infection in immunosuppressed indivi...
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These epitomes were introduced with the thought that comparative medicine is based on the concept humans and animals often share the same disease. Although the concept has been suggested in the past, the development of genetically engineered mice (GEM) has brought this concept into breathtaking reality. The sometimes rather vague morphological and...
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The human and simian immunodeficiency virus (HIV-1 and SIVmac) transmembrane proteins contain unusually long intracytoplasmic domains (ICD-TM). These domains are suggested to play a role in envelope fusogenicity, interaction with the viral matrix protein during assembly, viral infectivity, binding of intracellular calmodulin, disruption of membrane...
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Despite recent insights into mucosal human immunodeficiency virus (HIV) transmission, the route used by primate lentiviruses to traverse the stratified squamous epithelium of mucosal surfaces remains undefined. To determine if dendritic cells (DC) are used by primate lentiviruses to traverse the epithelial barrier of the genital tract, rhesus macaq...
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Development of an effective preventive or therapeutic vaccine against HIV-1 is an important goal in the fight against AIDS. Effective virus clearance and inhibition of spread to target organs depends principally on the cellular immune response. Therefore, a vaccine against HIV-1 should elicit virus-specific cytotoxic lymphocyte (CTL) responses to e...
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Variability of the major antigenic sites of the envelope glycoprotein of HIV-1 constitutes a major problem in the formulation of effective vaccines. We have prepared a synthetic peptide vaccine that represents the major hypervariable epitopes (V1 through V5) of the clade B HIV-1 envelope glycoprotein (gp120). We refer to this preparation as variabl...
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We vaccinated 4 groups of macaques with several forms of SIV envelope antigens expressed from plasmid DNA. One group was later boosted with recombinant protein antigen and another group was further vaccinated with a noninfectious proviral DNA. We found protection in approximately half of the animals after oral challenge with pathogenic SlVMAC (251)...
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Using synthetic peptides, we developed an approach to account for protein epitope variability. We have prepared, in a single synthesis, a cocktail of peptides we have designated a hypervariable epitope construct (HEC), which collectively represents much of the in vivo variability seen in an epitope. Eight HECs representing the in vivo variability s...
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In year two of this project we have developed and characterized four novel SIV envelope expression vectors and one vector expressing both envelope and core components for genetic immunization of rhesus monkeys. Experiments using test antigens to determine optimum DNA vaccine parameters are near completion. Beginning in January 1997 we will test one...
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Retrospective data indicate that two separate outbreaks of simian AIDS and associated lymphoma were caused by Simian Immunodeficiency Virus (SIVmac and SIVstm, respectively) in group-housed macaques at the California Regional Primate Research Center (CRPRC) in the early and mid-1970s. Because these epizootics were not then recognized as infectious...
Article
To evaluate the role of humoral immunity against simian immunodeficiency virus (SIV), we tested whether passive immunization with plasma from SIVmac251 vaccine-protected or healthy infected animals would protect rhesus monkeys against intravenous infection with ten 50% animal infectious doses of the cell-free homologous virus. The challenge dose of...
Article
A cohort of rhesus macaques (Macaca mulatta), obtained from the California Regional Primate Research Center (CRPRC) and necropsied in 1970-72 with lesions suggestive of simian immunodeficiency virus (SIV) infection, was identified at the New England Regional Primate Research Center (NERPRC). Polymerase chain reaction (PCR), DNA sequence analysis, a...
Article
The simian and feline immunodeficiency lentivirus infections of captive macaques and domestic cats (SIV and FIV, respectively) are excellent models for HIV infection of humans (Gardner and Luciw 1989). Among the animal lentiviruses, SIV is the most closely related to HIV and both SIV and FIV models manifest a disease pattern and viral encephalopath...
Article
To demonstrate that antibodies against amino acids (aa) 603-622 of the SIV gp41 transmembrane glycoprotein enhance infection of SIV in vivo. A synthetic peptide derived from aa 603-622 of SIVmac251 gp41 was synthesized and tested for immunogenicity in rabbits and SIV-infected rhesus macaques. Next, SIV-naive animals were immunized with either a rec...
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Epitope variability is one of the greatest obstacles to development of synthetic peptide vaccines. Based on a recently described hypervariable epitope (aa 414-434) on the envelope glycoprotein (gp130) to simian immunodeficiency virus (SIVmac142), we have developed a novel approach to account for epitope variability. We have prepared, in a single sy...
Article
As a safe alternative to inactivated and live-attenuated whole-virus SIV vaccines, we have evaluated the potential of SIVmac239 gp160 expressed by recombinant vaccinia virus (vSIVgp160) and baculovirus (bSIVgp160) to protectively immunize rhesus macaques against intravenous (i.v.) infection with pathogenic SIVmac isolates. Macaques were immunized w...
Article
Passive immunization with plasma from an inactivated-whole SIVmac vaccine protected monkey conferred complete or partial protection to rhesus macaques challenged intravenously 4 or 18 hours later with 10 AID50 of homologous cell-free virus. In contrast, passive immunization with inactivated plasma or purified immunoglobulin (Ig) from SIVmac infecte...
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The chapter presents a description of retroviruses and wild mice. Then, it discusses about the trapping of wild mice and establishment of aging populations in the laboratory. The chapter also discusses about spontaneous cancer, lymphoma, motor neuron disease, and Type C retrovirus (Mu LV) infection in aging wild mice, first in case of cancer-resist...
Chapter
Two genera of simian retrovirus cause fatal immunosuppressive disease in macaques: the simian immunodeficiency lentiviruses (SIV) and the type D simian retroviruses (SRV). Simian retroviruses belonging to the exogenous oncovirus, e.g., simian T-lymphotropic virus (STLV), and spumavirus genus, e.g., simian foamy virus, are described in other chapter...
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In view of the importance of cell-associated virus in AIDS virus transmission, an HIV vaccine should be able to induce a virus-specific CTL response. Traditional subunit vaccines have not elicited virus-specific CD8+ MHC class I-restricted CTL. We have used the simian immunodeficiency virus of macaques (SIVmac)/rhesus monkey model to explore the us...
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We have tested synthetic peptides composed of Th (T1) and V3 loop B cell neutralizing determinants [SP10 MN(A)] of HIVMN gp120 and the fusogenic (F) domain of gp41 as immunogens in rhesus monkeys. After two immunizations with either HIV env peptide T1-SP10 MN(A) or F-T1-SP10 MN(A), rhesus monkey serum neutralization titers against the HIVMN isolate...
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SIVmac infection of macaques is an important animal model for HIV infection and AIDS; this model is being utilized for development of antiviral therapies and vaccines. In the present article, we sought to identify neutralization epitopes of SIVmac envelope surface glycoprotein (gp130). Algorithms were used to predict antigenicity of specific region...
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All six cats passively immunized with sera from either feline immunodeficiency virus (FIV)-vaccinated cats or cats infected with FIV (Petaluma strain) were protected from homologous FIV infection at a challenge dose that infected all six control cats. Passive immunization with sera from cats vaccinated with uninfected allogeneic T cells used to gro...
Article
Several decades have lapsed since the original description of retroviral infection of the central nervous system (CNS) appeared. With the recent arrival of the autoimmune deficiency syndrome (AIDS) epidemic and the associated human retroviral encephalitis, interest in murine models has been rekindled. In most of the published studies, susceptible m...
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Simian immunodeficiency virus (SIV) infection of rhesus macaques is a model for human immunodeficiency virus (HIV) infection in humans. Inactivated and modified live whole-virus vaccines have provided limited protective immunity against SIV in rhesus macaques. Because of safety concerns in the use of inactivated and live whole-virus vaccines, we ev...
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Retroviruses have been the common foe in two recent “wars,” first against cancer, then against AIDS. Although neither war is close to over, some battles have been won, thanks in part to research using nonhuman primates. As useful as these animals were in studying retroviruses and cancer, their contribution to AIDS research is already far greater. T...
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More than 90% of cats immunized with inactivated whole infected-cell or cell-free feline immunodeficiency virus (FIV) vaccines were protected against intraperitoneal infection with 10 50% animal infectious doses of either homologous FIV Petaluma (28 of 30 cats) or heterologous FIV Dixon strain (27 of 28 cats). All 15 control cats were readily infec...
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Different populations of wild mice (Mus musculus domesticus) in Los Angeles and Ventura Counties were observed over their lifespan in captivity for expression of infectious murine leukemia virus (MuLV) and murine mammary tumor virus (MMTV) and for the occurrence of cancer and other diseases. In most populations of feral mice these indigenous retrov...
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We analyzed SIV-specific monkey sera to localize B-cell epitopes of the envelope glycoprotein of SIV (gp130), using overlapping synthetic peptides representing the entire SIV gp130 protein and sera from experimentally infected monkeys and monkeys immunized with whole, inactivated SIV. A B-cell epitope which induces neutralizing antibody production...
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Rhesus macaques were immunized with live vaccinia virus recombinants expressing the envelope glycoproteins (gp70 and gp22) of simian type D retrovirus (SRV), serotype 1 or 3. All of the animals immunized with either the SRV-1 env or the SRV-3 env vaccinia virus recombinant developed neutralizing antibodies against the homologous SRV. In addition, b...
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We have developed a method for attenuating vaccinia virus recombinants by expressing a fusion protein of a lymphokine and an immunogen. Chimeric genes were constructed that coded for gamma interferon (IFN-gamma) and structural proteins of the human immunodeficiency virus type 1 (HIV-1). In this study, we describe the biological and immunological pr...
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Sera from SIV-infected macaques were found to contain antibodies that reacted with conformation-dependent, group-specific determinants on the SIV envelope protein gp130. These conformation-dependent antibodies exhibited virus neutralizing activity; their presence was associated with protection in vaccine studies. The properties of these antibodies...
Article
A retrospective study determined that an epizootic of immune suppression and lymphoma in stump-tailed macaques (Macaca arctoides) that began in 1976 was associated with a horizontally spread lentivirus infection. This conclusion was based on serology, epidemiology, pathology, and virus isolation. The lesions found in the stump-tailed macaques were...
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We report here the results of molecular analysis of a simian immunodeficiency virus (designated SIVstm) which was isolated from a rhesus monkey inoculated with stored lymph node tissue of an Asian stump-tailed macaque. The latter monkey had died in 1977 during an epidemic of acquired immunodeficiency and lymphoma at the California Regional Primate...
Chapter
The prominent neurological manifestations associated with infection by the human immunodeficiency virus (HIV) and the human T-lymphotropic retrovirus (HTLV) have focused attention on the neurotropic properties of the family Retroviridae. This family is divided into three subfamilies, the oncoviruses, the lentiviruses, and the spumaviruses, each of...
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Simian immunodeficiency virus (SIV), a lymphocytopathic lentivirus, induces an AIDS-like disease in rhesus macaques (Macaca mulatta). A pathogenic molecular clone of rhesus macaque SIV (SIVmac), SIVmac-239, replicates and induces cytopathology in T lymphocytes but is restricted for replication in macrophages. In contrast, a nonpathogenic molecular...
Article
SIV vaccines made of inactivated whole virus, modified live virus and native and recombinant envelope antigens have protected macaques against experimental infection with low doses of cell-free SIV given systemically. The few vaccinated monkeys that do become infected have tended to live longer than the infected controls. Protection against cell-as...
Article
Retroviral envelope glycoproteins interact with cell receptors and are targets for antiviral immune responses in infected hosts. Macaque simian immunodeficiency virus (SIVmac) is a T-lymphocytopathic lentivirus which causes an AIDS-like disease in rhesus macaques. The envelope gene of SIVmac encodes a precursor glycoprotein (gp160) which is cleaved...
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A simian type D retrovirus designated SRV induces a fatal immunosuppressive disease in rhesus macaques. This syndrome shows many clinical similarities to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus-infected individuals. To investigate the mechanisms of immune dysfunction in SRV infection, we have focused on the interac...
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Infection of domestic cats with the feline immunodeficiency virus (FIV) represents an important veterinary health problem and a useful animal model for the development of vaccines against acquired immunodeficiency syndrome (AIDS). Two experimental FIV vaccines have been developed; one consisting of fixed infected cells (Vaccine 1), the other of ina...
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The functional characteristics of polymorphonuclear leukocytes (PMN), considered to be the first line of host defense against infections, from rhesus macaques confirmed to have simian retrovirus (SRV)-induced simian acquired immunodeficiency syndrome (SAIDS), were evaluated. The PMN from SRV antibody-positive macaques without clinical signs were ch...