Demma Linda J, Logsdon John M, Vanderford Thomas H, Feinberg Mark B, Staprans Silvija I
Department of Biology, Emory University, Atlanta, Georgia, United States of America.
PLoS Pathog. 2005 Sep;1(1):e3. doi: 10.1371/journal.ppat.0010003. Epub 2005 Sep 30.
Despite the potential for infectious agents harbored by other species to become emerging human pathogens, little is known about why some agents establish successful cross-species transmission, while others do not. The simian immunodeficiency viruses (SIVs), certain variants of which gave rise to the human HIV-1 and HIV-2 epidemics, have demonstrated tremendous success in infecting new host species, both simian and human. SIVsm from sooty mangabeys appears to have infected humans on several occasions, and was readily transmitted to nonnatural Asian macaque species, providing animal models of AIDS. Here we describe the first in-depth analysis of the tremendous SIVsm quasispecies sequence variation harbored by individual sooty mangabeys, and how this diverse quasispecies adapts to two different host species-new nonnatural rhesus macaque hosts and natural sooty mangabey hosts. Viral adaptation to rhesus macaques was associated with the immediate amplification of a phylogenetically related subset of envelope (env) variants. These variants contained a shorter variable region 1 loop and lacked two specific glycosylation sites, which may be selected for during acute infection. In contrast, transfer of SIVsm to its natural host did not subject the quasispecies to any significant selective pressures or bottleneck. After 100 d postinfection, variants more closely representative of the source inoculum reemerged in the macaques. This study describes an approach for elucidating how pathogens adapt to new host species, and highlights the particular importance of SIVsm env diversity in enabling cross-species transmission. The replicative advantage of a subset of SIVsm variants in macaques may be related to features of target cells or receptors that are specific to the new host environment, and may involve CD4-independent engagement of a viral coreceptor conserved among primates.
尽管其他物种携带的感染因子有可能成为新出现的人类病原体，但对于为何有些因子能成功实现跨物种传播而有些不能，我们却知之甚少。猿猴免疫缺陷病毒（SIVs），其某些变体引发了人类HIV - 1和HIV - 2的流行，在感染新的宿主物种（包括猿猴和人类）方面已显示出巨大的成功。来自乌黑白眉猴的SIVsm似乎曾多次感染人类，并能轻易传播给非天然的亚洲猕猴物种，从而提供了艾滋病动物模型。在此，我们描述了对单个乌黑白眉猴所携带的巨大SIVsm准种序列变异的首次深入分析，以及这种多样的准种如何适应两种不同的宿主物种——新的非天然恒河猴宿主和天然的乌黑白眉猴宿主。病毒对恒河猴的适应与包膜（env）变体的一个系统发育相关亚群的迅速扩增有关。这些变体的可变区1环较短，并且缺少两个特定的糖基化位点，这可能是在急性感染期间被选择的。相比之下，SIVsm转移到其天然宿主时，准种并未受到任何显著的选择压力或瓶颈效应。感染后100天，猕猴体内重新出现了更能代表原始接种物的变体。这项研究描述了一种阐明病原体如何适应新宿主物种的方法，并突出了SIVsm env多样性在实现跨物种传播中的特殊重要性。SIVsm变体亚群在猕猴中的复制优势可能与新宿主环境特有的靶细胞或受体特征有关，并且可能涉及灵长类动物中保守的病毒共受体的非CD4依赖性结合。
