Abstract:
SIV pathogenesis studies have been restricted primarily to viruses isolated from sooty mangabeys (SIVsm) or macaques (SIVmac) since these viruses induce immunodeficiency similar to human AIDS in inoculated macaques. In contrast, infection of macaques with SIV isolated from African green monkeys (SIVagm) generally results in transient viremia with no associated disease, leading some to suggest that SIVagm is nonpathogenic. However, we previously observed CD4 depletion and Mycobacterium infection in a pig-tailed macaque (Macaca nemestrina) inoculated with SIVagm isolated from a naturally infected vervet monkey (Cercopithecus pygerythrus). Terminally, virus was isolated from the spleen in CEMss cells, and this isolate was designated SIVagm9063. The goal of the present study was to characterize the pathogenic and molecular properties of this novel SIVagm strain. Pig-tailed macaques, rhesus macaques, and African green monkeys were inoculated intravenously with SIVagm9063. All three species became infected, however, only pig-tailed macaques developed an AIDS-like syndrome with a progressive decline in circulating CD4 lymphocytes. Three of these macaques were sacrificed within 1 year of inoculation due to opportunistic infections. In parallel studies, genomic DNA derived from the SIVagm9063 isolate was used to generate a lambda library and derive two infectious clones. Sequence analysis showed that this virus clustered with other vervet isolates but was genetically distinct. Progeny virus derived by transfection of either clone infected macaque PBMC and macrophages in culture and resulted in persistent infection in pig-tailed macaques. Although animal studies are preliminary, an early, persistent decline in CD4 cells in the blood suggest that these cloned viruses are representative of the parental strain in virulence. This study demonstrates that some SIVagm strains induce AIDS in experimentally-infected macaques and will provide a basis for studying host and virus specific factors in pathogenicity.
Keywords: Acquired Immunodeficiency Syndrome/MICROBIOLOGY Animal Antigens, CD4/BLOOD Cercopithecus aethiops/*MICROBIOLOGY DNA, Viral/ANALYSIS/GENETICS Genome, Viral Human Macaca mulatta/*MICROBIOLOGY Macaca nemestrina/*MICROBIOLOGY Simian Acquired Immunodeficiency Syndrome/IMMUNOLOGY/ *MICROBIOLOGY Species Specificity SIV/GENETICS/*ISOLATION & PURIF/*PATHOGENICITY T-Lymphocyte Subsets/IMMUNOLOGY Virulence ABSTRACT 940730
M9470897
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