Bannert N, Schenten D, Craig S, Sodroski J
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Virol. 2000 Dec;74(23):10984-93. doi: 10.1128/jvi.74.23.10984-10993.2000.
The entry of primate immunodeficiency viruses into cells is dependent on the interaction of the viral envelope glycoproteins with receptors, CD4, and specific members of the chemokine receptor family. Although in many cases the tropism of these viruses is explained by the qualitative pattern of coreceptor expression, several instances have been observed where the expression of a coreceptor on the cell surface is not sufficient to allow infection by a virus that successfully utilizes the coreceptor in a different context. For example, both the T-tropic simian immunodeficiency virus (SIV) SIVmac239 and the macrophagetropic (M-tropic) SIVmac316 can utilize CD4 and CCR5 as coreceptors, and both viruses can infect primary T lymphocytes, yet only SIVmac316 can efficiently infect CCR5-expressing primary macrophages from rhesus monkeys. Likewise, M-tropic strains of human immunodeficiency virus type 1 (HIV-1) do not infect primary rhesus monkey macrophages efficiently. Here we show that the basis of this restriction is the low level of CD4 on the surface of these cells. Overexpression of human or rhesus monkey CD4 in primary rhesus monkey macrophages allowed infection by both T-tropic and M-tropic SIV and by primary M-tropic HIV-1. By contrast, CCR5 overexpression did not specifically compensate for the inefficient infection of primary monkey macrophages by T-tropic SIV or M-tropic HIV-1. Apparently, the limited ability of these viruses to utilize a low density of CD4 for target cell entry accounts for the restriction of these viruses in primary rhesus monkey macrophages.
灵长类免疫缺陷病毒进入细胞依赖于病毒包膜糖蛋白与受体、CD4以及趋化因子受体家族特定成员之间的相互作用。尽管在许多情况下，这些病毒的嗜性可通过共受体表达的定性模式来解释，但已观察到一些实例，即细胞表面共受体的表达不足以使在其他情况下能成功利用该共受体的病毒进行感染。例如，T嗜性猴免疫缺陷病毒（SIV）SIVmac239和巨噬细胞嗜性（M嗜性）SIVmac316都可利用CD4和CCR5作为共受体，且这两种病毒都能感染原代T淋巴细胞，但只有SIVmac316能有效感染恒河猴表达CCR5的原代巨噬细胞。同样，1型人类免疫缺陷病毒（HIV-1）的M嗜性毒株也不能有效感染原代恒河猴巨噬细胞。在此我们表明，这种限制的基础是这些细胞表面CD4水平较低。在原代恒河猴巨噬细胞中过表达人或恒河猴CD4可使T嗜性和M嗜性SIV以及原代M嗜性HIV-1进行感染。相比之下，过表达CCR5并不能特异性补偿T嗜性SIV或M嗜性HIV-1对原代猴巨噬细胞感染效率低下的问题。显然，这些病毒利用低密度CD4进入靶细胞的能力有限，这导致了这些病毒在原代恒河猴巨噬细胞中的限制。
