PRIMARY SIV INFECTION DYNAMICS IN AFRICAN AND ASIAN MONKEYS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 目的：分析SIV在非洲非人灵长类动物中的初次感染动态，并确定其与猕猴中致病性SIV感染的主要差异。 方法：用SIV接种5种非洲（N=43）和亚洲（N=43）NHP。使用频繁采样的血浆RNA病毒载量（VL）和外周血CD 4+淋巴细胞计数的数学建模允许估计感染参数值。 结果如下：非洲和亚洲NHP的峰值病毒血症平均水平（9 <$1天时为7.5 <$0.7 log拷贝RNA/mL）和病毒稳态水平相似（5.4 <$1.1 log拷贝RNA/mL）。指数生长阶段的病毒倍增时间（平均10 - 3天）在所有物种中相似。在急性SIV感染期间，所有物种的CD 4+淋巴细胞下降的程度相似。然而，非洲猴的VL下降速度更快，表明非致病性感染的峰值后感染细胞损失率比致病性感染更快（P0.001），表明非洲NHP中感染细胞的半衰期（0.8 <$0.3天）比亚洲NHP（2.7 <$1.6天）短。与亚洲同行相比，非洲NHP中继发感染的数量要低得多，导致这些动物中感染细胞的百分比较低。 结论：分析表明，非洲国家卫生保健人员比亚洲国家卫生保健人员更快达到病毒设定点。我们的模型表明，这是由于与亚洲NHP相比，非洲NHP中生产性感染细胞的损失更快。

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.