PRIMARY SIV INFECTION DYNAMICS IN AFRICAN AND ASIAN MONKEYS

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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. Objective: To analyze the primary infection dynamics of natural SIV infection among African non-human primates (NHPs) and to identify the major differences with pathogenic SIV infection in macaques. Methods: Five species of African (N=43) and Asian (N=43) NHPs were inoculated with SIV. Mathematical modeling using frequently sampled plasma RNA viral loads (VLs) and peripheral CD4+ lymphocyte counts allowed estimation of infection parameter values. Results: The average levels of peak viremia (7.5¿0.7 log copies RNA/mL at 9¿1 days) and viral steady state levels were similar in the African and Asian NHPs (5.4¿1.1 log copies RNA/mL). The exponential growth stage had viral doubling times (average 10¿3 days) similar in all species. The CD4+ lymphocytes declined to similar extent in all species during acute SIV infection. However, the decline in VL was faster in African monkeys indicating that the infected cell loss rate following the peak was faster in nonpathogenic than pathogenic infections (P0.001), indicating that the infected cell half-lifes were shorter in African NHPs (0.8¿0.3 days) than in Asian NHPs (2.7¿1.6 days). The number of secondary infections was much lower in African NHPs leading to a lower percentage of infected cells in these animals compared with their Asian counterparts. Conclusions: The analysis shows that the viral setpoint is reached more rapidly in African than in Asian NHPs. Our modeling suggests that this is due to a more rapid loss of productively infected cells in Africans NHPs as compared to Asian NHPs.