Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q3V6T2 (ape)
 2,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two strains of feline leukemia virus, two endogenous feline type-C viruses (RD/CCC group), several endogenous and laboratory strains of murine "leukemia" virus, two rat viruses, two primate viruses (woolly monkey and gibbon ape), as well as hamster, pig, and avian type-C viruses were examined for their relatedness to one another by molecular hybridization. The extent of nucleic-acid homology was determined by hybridization of the various viral RNAs to a [(3)H]DNA product synthesized from each virus. Among the murine type-C viruses (Rauscher, Kirsten, AT-124, and endogenous BALB/c virus) a high degree of homology is observed, although the viruses are not identical. The two primate viruses are also closely related to one another. The feline, rat, hamster, and pig endogenous viruses can be readily distinguished from one another and from the murine and primate viruses since their DNA products share very little or no nucleic-acid homology. However, the murine and primate type-C virus groups possess a surprising degree of relatedness. Feline type-C viruses fall into two distinct groups, the feline leukemia virus group and the RD-114/CCC group, with little detectable nucleic-acid homology between them. Infection of feline or rat cells with type-C virus results in production of the endogenous type-C virus of the species along with the infecting virus.
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PMID:Homology between type-C viruses of various species as determined by molecular hybridization. 435 65

Infection with a replication-competent bovine leukemia virus structural gene vector (BLV SGV) is an innovative vaccination approach to prevent disease by complex retroviruses. Previously we developed BLV SGV that constitutively expresses BLV gag, pol, and env and related cis-acting sequences but lacks tax, rex, RIII, and GIV and most of the BLV long terminal repeat sequences, including the cis-acting Tax and Rex response elements. The novel SGV virus is replication competent and replicates a selectable vector to a titer similar to that of the parental BLV in cell culture. The overall goal of this study was to test the hypothesis that infection with BLV SGV is nonpathogenic in rabbits. BLV infection of rabbits by inoculation of cell-free BLV or cell-associated BLV typically causes an immunodeficiency-like syndrome and death by 1 year postinfection. We sought to evaluate whether in vivo transfection of BLV provirus recapitulates pathogenic BLV infection and to compare BLV and BLV SGV with respect to infection, immunogenicity, and clinical outcome. Three groups of rabbits were subjected to in vivo transfection with BLV, BLV SGV, or negative control DNA. The results of our 20-month study indicate that in vivo transfection of rabbits with BLV recapitulates the fatal BLV infection produced by cell-free or cell-associated BLV. The BLV-infected rabbits exhibited sudden onset of clinical decline and immunodeficiency-like symptoms that culminated in death. BLV and BLV SGV infected peripheral blood mononuclear cells and induced similar levels of seroconversion to BLV structural proteins. However, BLV SGV exhibited a reduced proviral load and did not trigger the immunodeficiency-like syndrome. These results are consistent with the hypothesis that BLV SGV is infectious and immunogenic and lacks BLV pathogenicity in rabbits, and they support the use of this modified proviral vector delivery system for vaccines against complex retroviruses like BLV.
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PMID:Bovine leukemia virus structural gene vectors are immunogenic and lack pathogenicity in a rabbit model. 1048 66

Expression of suicide genes (e.g. herpes simplex virus thymidine kinase,HSV-TK) in T cells is an appealing approach to regulate graft-versus-host disease in adoptive immunotherapy. Here we report the optimization of retroviral infection of canine T cells. Canine T cells were stimulated either with phytohemagglutinin (PHA, 2 microg/ml) for 24-72 hours or with 100 U/ml interleukin-2 for seven days. Stimulated cells were co-cultivated with irradiated virus-producing cells. Transduction efficiencies ranged from 4% to 45% using PG13, a gibbon ape leukemia virus envelope (env) pseudotyped packaging cell line. Infection of cells with GPenvAM12, expressing the amphotropic Moloney murine leukemia virus env, did not yield a satisfactory percentage of transduced cells. Enrichment of transduced cells was performed using immunoselection, and gave a purity of up to 98%. Transfusion of 1 x 10(6) transduced cells per kilogram body weight showed that transduced cells could convert mixed chimerism to 100% and transfer immunity to a specific antigen. Transduced cells were repeatedly detected in peripheral blood and bone marrow by polymerase chain reaction with primers specific for the HSV-TK gene. We have demonstrated the feasibility of using the canine model to study gene therapy as a preclinical model.
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PMID:Expression of HSV-TK suicide gene in primary T lymphocytes: the dog as a preclinical model. 1097 36

Infection with hepatitis B virus (HBV) has been detected in human populations throughout the world, as well as in a number of ape species (Pan troglodytes, Gorilla gorilla, gibbons [Nomascus and Hylobates species] and Pongo pygmaeus). To investigate the distribution of naturally occurring HBV infection in these species and other African Old World monkey species (Cercopithecidae), we screened 137 plasma samples from mainly wild caught animals by polymerase chain reaction (PCR) using several of highly conserved primers from the HB surface (HBs) gene, and for HBs antigen (HBsAg) by ELISA. None of the 93 Cercopithecidae screened (6 species) showed PCR or serology evidence for HBV infection; in contrast 2 from 8 chimpanzees and 5 from 22 gibbons were PCR-positive with each set of primers. Complete genome sequences from each of the positive apes were obtained and compared with all previously published complete and surface gene sequences. This extended phylogenetic analysis indicated that HBV variants from orangutans were interspersed by with HBV variants from southerly distributed gibbon species (H. agilis and H. moloch) occupying overlapping or adjacent habitat ranges with orangutans; in contrast, HBV variants from gibbon species in mainland Asia were phylogenetically distinct. A geographical rather than (sub)species association of HBV would account for the distribution of HBV variants in different subspecies of chimpanzees in Africa, and explain the inlier position of the previously described lowland gorilla sequence in the chimpanzee clade. These new findings have a number of implication for understanding the origins and epidemiology of HBV infection in non-human primates.
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PMID:Geographic and species association of hepatitis B virus genotypes in non-human primates. 1451 90

Infection of a host cell by a retrovirus requires an initial interaction with a cellular receptor. For numerous gammaretroviruses, such as the gibbon ape leukemia virus, woolly monkey virus, feline leukemia virus subgroup B, feline leukemia virus subgroup T, and 10A1 murine leukemia virus, this receptor is the human type III sodium-dependent inorganic phosphate transporter, SLC20A1, formerly known as PiT1. Understanding the critical receptor functionalities and interactions with the virus that lead to successful infection requires that we first know the surface structure of the cellular receptor. Previous molecular modeling from the protein sequence, and limited empirical data, predicted a protein with 10 transmembrane helices. Here we undertake the biochemical approach of substituted cysteine accessibility mutagenesis to resolve the topology of this receptor in live cells. We discover that there are segments of the protein that are unexpectedly exposed to the outside milieu. By using information determined by substituted cysteine accessibility mutagenesis to set constraints in HMMTOP, a hidden Markov model-based transmembrane topology prediction method, we now propose a comprehensive topological model for SLC20A1, a transmembrane protein with 12 transmembrane helices and 7 extracellular regions, that varies from previous models and should permit approaches that define both virus interaction and transport function.
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PMID:New structural arrangement of the extracellular regions of the phosphate transporter SLC20A1, the receptor for gibbon ape leukemia virus. 1971 69

Should monkeys be used in painful and often deadly infectious disease research that may save many human lives? This is the challenging question that Anne Barnhill, Steven Joffe, and Franklin G. Miller take on in their carefully argued and compelling article "The Ethics of Infection Challenges in Primates." The authors offer a nuanced and even-handed position that takes philosophical worries about nonhuman primate moral status seriously and still appreciates the very real value of such research for human welfare. Overall, they argue for an extension and revision of the recommendations regarding chimpanzee research offered by the Institute of Medicine in 2011; the practical upshot of their argument would allow for infection challenge research for promising interventions for Ebola and Marburg virus diseases but not for smallpox or the common cold. The IOM recommendations regarding chimpanzee research put in motion an exceptionalist policy for this great ape population. Barnhill and colleagues' proposal would enlarge the scope of that exceptionalism to embrace NHPs other than great apes. But is such exceptionalism warranted? It is not obvious to me either that the more sophisticated capacities of a species as a whole give it greater ethical protections or that less intellectually or socially sophisticated animals ought to therefore receive less protection when it comes to painful experimental interventions.
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PMID:Beyond Primates: Research Protections and Animal Moral Value. 2741 67

Gibbon ape leukemia virus (GALV) can infect a wide variety of cells but fails to infect most cells derived from laboratory mice. Transduction of human hematopoietic stem cells with GALV retroviral vectors is more efficient than with amphotropic vectors. In this study, a Moloney murine leukemia virus-gibbon ape leukemia virus (MoMLV-GALV) vector was constructed by replacing the natural env gene of the full-length Moloney MLV genome with the GALV env gene. To monitor viral transmission by green fluorescent protein (GFP) expression, internal ribosomal entry site-enhanced GFP (IRES-EGFP) was positioned between the GALV env gene and the 3' untranslated region (3' UTR) to obtain pMoMLV-GALV-EGFP. The MoMLV-GALV-EGFP vector was able to replicate with high titer in TE671 human rhabdomyosarcoma cells and U-87 human glioma cells. To evaluate the potential of the MoMLV-GALV vector as a therapeutic agent, the gene for the fusogenic envelope G glycoprotein of vesicular stomatitis virus (VSV-G) was incorporated into the vector. Infection with the resulting MoMLV-GALV-VSV-G vector resulted in lysis of the U-87 cells due to syncytium formation. Syncytium formation was also observed in the transfected human prostate cancer cell line LNCaP after extended cultivation of cells. In addition, we deleted the GALV env gene from the MoMLV-GALV-VSV-G vector to improve viral genome stability. This MoMLV-VSV-G vector is also replication competent and induces syncytium formation in 293T, HT1080, TE671 and U-87 cells. These results suggest that replication of the MoMLV-GALV-VSV-G vector or MoMLV-VSV-G vector may directly lead to cytotoxicity. Therefore, the vectors developed in this study are potentially useful tools for cancer gene therapy.
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PMID:Construction of a replication-competent retroviral vector for expression of the VSV-G envelope glycoprotein for cancer gene therapy. 3214 6