This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Four SIV challenge stocks were prepared and titered for in vivo infectivity in M. nemestrina. SIVmneClone 8 is a moderately pathogenic molecular clone of the prototype SIVmne E11S. SIVmne170 is a highly pathogenic molecular clone from a late isolate of a Clone 8-infected animal. Chimera 170/8 contains the 5? half of the viral genome of SIVmneWk170 and the 3? half of CL8, whereas chimera 8/170 represents the reciprocal construct. These viruses represent a set of molecularly defined viruses with distinct biological phenotypes. Sixteen M. nemestrina were inoculated intravenously with serial dilutions of these challenge stocks and peripheral blood was collected periodically to determine plasma and PBMC viral load and CD4 cell counts. From animals that did not show any detectable virus in the peripheral blood, we collected lymph nodes and assayed for proviral sequences to confirm their uninfected status. Based on the numbers of animals inoculated and infected (or uninfected) at each serial dilution, we used the VacMan program (Spouge, Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7581-5) to determine the 50% animal infectious dose of the challenge virus. The AID50 for the CL8, 170, 8/170 and 170/8 challenge stock have been determined to be: 4.0?104/ml , 7.1?104/ml 4.2?105/ml 1.3?104/ml, respectively Virological, immunologic and clinical analyses showed that the four SIVmne viruses had distinct outcomes after infection. CL8 infection resulted in low plasma viral load that was persistent only in a fraction of the infected animals, all of which survived without clinical symptoms of AIDS for 1 year. On the other hand, 170 Wk infected animals had high viral load and rapid CD4+ T cell depletion. Infection by either chimeras resulted high plasma viral loads, indicating that determinants in both gag and env contribute to the virulence and pathogenicity of SIVmne.
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