![]() |
![]() |
||||||||||||
|
02467 A PATHOGENIC CCR5-UTILIZING SHIV162PT CAN IMPROVE MACAQUE MODEL FOR TOPICAL MICROBICIDE EVALUATION Tsai, Che-Chung Improved animal models that have biologic and virologic relevance to human HIV infection would facilitate current research. Rhesus macaques challenged with a chimeric CCR5-utilizing SIV/HIV, SHIV162P3, have been used to evaluate topical microbicides. However, vaginal challenge of pigtailed macaques (Macaca nemestrina; Mne) with SHIV162P3 results in poor infectivity and non-persistent replication. To improve these viral characteristics, we serially passaged SHIV162P3 in four adult female Mne. The first animal (P1) was inoculated intravenously with both cell-free and cell-associated SHIV162P3 grown in Mne PBMCs. Two weeks after inoculation, 10 ml of whole blood from P1 were transferred to a second macaque (P2). This passage schedule was performed consecutively in two additional macaques (P3 and P4). The animals were clinically monitored and lab assays were performed on blood samples. Results indicated that SHIV162P3 evolved during passage to a variant (SHIV162Pt) with increased infectivity and pathogenicity. SHIV162Pt was propagated in macaque PBMCs. Virus from this stock replicates in macaque and human PBMCs and CCR5+ cell lines but does not replicate in CXCR4+ cell lines. Evaluation of this stock in vivo should indicate whether this SHIV can improve the Mne model for topical microbicide evaluation. (This work supported by NIH Contract NO1-AI-15450). Dr. Che-Chung Tsai |
|||||||||||||