Diop O M, Gueye A, Dias-Tavares M, Kornfeld C, Faye A, Ave P, Huerre M, Corbet S, Barre-Sinoussi F, Müller-Trutwin M C
Laboratoire de Rétrovirologie, Institut Pasteur, Dakar, Senegal.
J Virol. 2000 Aug;74(16):7538-47. doi: 10.1128/jvi.74.16.7538-7547.2000.
In contrast to pathogenic human immunodeficiency virus and simian immunodeficiency virus (SIV) infections, chronic SIVagm infections in African green monkeys (AGMs) are characterized by persistently low peripheral and tissue viral loads that correlate with the lack of disease observed in these animals. We report here data on the dynamics of acute SIVagm infection in AGMs that exhibit remarkable similarities with viral replication patterns observed in peripheral blood during the first 2 weeks of pathogenic SIVmac infections. Plasma viremia was evident at day 3 postinfection (p.i.) in AGMs, and rapid viral replication led by days 7 to 10 to peak viremias characterized by high levels of antigenemia (1.2 to 5 ng of p27/ml of plasma), peripheral DNA viral load (10(4) to 10(5) DNA copies/10(6) peripheral blood mononuclear cells [PBMC]), and plasma RNA viral load (2 x 10(6) to 2 x 10(8) RNA copies/ml). The lymph node (LN) RNA and DNA viral load patterns were similar to those in blood, with peaks observed between day 7 and day 14. These values in LNs (ranging from 3 x 10(5) to 3 x 10(6) RNA copies/10(6) LN cell [LNC] and 10(3) to 10(4) DNA copies/10(6) LNC) were at no time point higher than those observed in the blood. Both in LNs and in blood, rapid and significant decreases were observed in all infected animals after this peak of viral replication. Within 3 to 4 weeks p. i., antigenemia was no longer detectable and peripheral viral loads decreased to values similar to those characteristic of the chronic phase of infection (10(2) to 10(3) DNA copies/10(6) PBMC and 2 x 10(3) to 2 x 10(5) RNA copies/ml of plasma). In LNs, viral loads declined to 5 x 10(1) to 10(3) DNA copies and 10(4) to 3 x 10(5) RNA copies per 10(6) LNC at day 28 p.i. and continued to decrease until day 84 p.i. (<10 to 3 x 10(4) RNA copies/10(6) LNC). Despite extensive viremia during primary infection, neither follicular hyperplasia nor CD8(+) cell infiltration into LN germinal centers was detected. Altogether, these results indicate that the nonpathogenic outcome of SIVagm infection in its natural host is associated with a rapidly induced control of viral replication in response to SIVagm infection, rather than with a poorly replicating virus or a constitutive host genetic resistance to virus replication.
与致病性人类免疫缺陷病毒和猿猴免疫缺陷病毒（SIV）感染不同，非洲绿猴（AGM）的慢性SIVagm感染的特征是外周血和组织中的病毒载量持续较低，这与这些动物未出现疾病相关。我们在此报告了AGM急性SIVagm感染的动态数据，这些数据与致病性SIVmac感染的前2周在外周血中观察到的病毒复制模式具有显著相似性。在AGM中，感染后第3天（p.i.）血浆病毒血症明显，到第7至10天快速的病毒复制导致病毒血症达到峰值，其特征为高水平的抗原血症（1.2至5 ng p27/毫升血浆）、外周血DNA病毒载量（10⁴至10⁵ DNA拷贝/10⁶外周血单个核细胞[PBMC]）和血浆RNA病毒载量（2×10⁶至2×10⁸ RNA拷贝/毫升）。淋巴结（LN）的RNA和DNA病毒载量模式与血液中的相似，在第7天至第14天之间出现峰值。LN中的这些值（范围为3×10⁵至3×10⁶ RNA拷贝/10⁶ LN细胞[LNC]和10³至10⁴ DNA拷贝/10⁶ LNC）在任何时间点都不高于血液中观察到的值。在LN和血液中，所有感染动物在病毒复制达到峰值后均观察到病毒载量迅速且显著下降。感染后3至4周内，抗原血症不再可检测到，外周病毒载量降至与感染慢性期特征相似的值（10²至10³ DNA拷贝/10⁶ PBMC和2×10³至2×10⁵ RNA拷贝/毫升血浆）。在LN中，感染后第28天病毒载量降至每10⁶ LNC 5×10¹至10³ DNA拷贝和10⁴至3×10⁵ RNA拷贝，并持续下降直至感染后第84天（<10至3×10⁴ RNA拷贝/10⁶ LNC）。尽管在初次感染期间存在广泛的病毒血症，但未检测到滤泡增生或CD8⁺细胞浸润到LN生发中心。总之，这些结果表明，SIVagm在其天然宿主中的非致病性结果与对SIVagm感染迅速诱导的病毒复制控制有关，而不是与复制能力差病毒或宿主对病毒复制的固有遗传抗性有关。
