Ylinen Laura M J, Keckesova Zuzana, Wilson Sam J, Ranasinghe Srinika, Towers Greg J
Wohl Virion Center, Division of Infection and Immunity, Windeyer Building, University College London, 46 Cleveland St., London W1T4JF, United Kingdom.
J Virol. 2005 Sep;79(18):11580-7. doi: 10.1128/JVI.79.18.11580-11587.2005.
Primate lentiviruses have narrow host ranges, due in part to their sensitivities to mammalian intracellular antiviral factors such as APOBEC3G and TRIM5alpha. Despite the protection provided by this innate immune system, retroviruses are able to transfer between species where they can cause disease. This is true for sooty mangabey simian immunodeficiency virus, which has transferred to humans as HIV-2 and to rhesus macaques as SIVmac, where it causes AIDS. Here we examine the sensitivities of the closely related HIV-2 and SIVmac to restriction by TRIM5alpha. We show that rhesus TRIM5alpha can restrict HIV-2 but not the closely related SIVmac. SIVmac has not completely escaped TRIM5alpha, as shown by its sensitivity to distantly related TRIM5alpha from the New World squirrel monkey. Squirrel monkey TRIM5alpha blocks SIVmac infection after DNA synthesis and is not saturable with restriction-sensitive virus-like particles. We map the determinant for TRIM5alpha sensitivity to the structure in the capsid protein that recruits CypA into HIV-1 virions. We also make an SIV, mutated at this site, which bypasses restriction in all cells tested.
灵长类慢病毒的宿主范围较窄，部分原因是它们对哺乳动物细胞内抗病毒因子如载脂蛋白B mRNA编辑酶催化多肽样蛋白3G（APOBEC3G）和TRIM5α敏感。尽管这种先天免疫系统提供了保护，但逆转录病毒仍能够在物种间传播并引发疾病。乌黑白眉猴猴免疫缺陷病毒就是如此，它已传播给人类成为HIV-2，并传播给恒河猴成为SIVmac，在这些宿主中引发艾滋病。在此，我们研究了密切相关的HIV-2和SIVmac对TRIM5α限制作用的敏感性。我们发现恒河猴TRIM5α能够限制HIV-2，但对密切相关的SIVmac却没有作用。SIVmac并未完全逃脱TRIM5α的限制，这从它对来自新世界松鼠猴的远亲TRIM5α敏感可以看出。松鼠猴TRIM5α在DNA合成后阻断SIVmac感染，并且对限制敏感的病毒样颗粒不饱和。我们将TRIM5α敏感性的决定因素定位到衣壳蛋白中能将亲环素A（CypA）招募到HIV-1病毒体中的结构上。我们还构建了在此位点发生突变的SIV，它在所有测试细胞中都能绕过限制作用。
