Utilization of chemokine receptors, orphan receptors, and herpesvirus-encoded receptors by diverse human and simian immunodeficiency viruses.
Utilization of chemokine receptors, orphan receptors, and herpesvirus-encoded receptors by diverse human and simian immunodeficiency viruses.
复制标题
多种人类和猿猴免疫缺陷病毒对趋化因子受体、孤儿受体和疱疹病毒编码受体的利用。
DOI：
10.1128/jvi.71.12.8999-9007.1997
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发表时间：
1997
影响因子：
5.4
通讯作者：
Doms,RW
中科院分区：
文献类型：
--
作者：
Rucker,J;Edinger,AL;Sharron,M;Samson,M;Lee,B;Berson,JF;Yi,Y;Margulies,B;Collman,RG;Doranz,BJ;Parmentier,M;Doms,RW
人类免疫缺陷病毒1型（HIV-1）需要CD 4和辅助受体来感染细胞。嗜巨噬细胞（M-嗜性）HIV-1毒株利用趋化因子受体CCR 5与CD 4结合感染细胞，而嗜T细胞（T-嗜性）毒株通常利用CXCR 4作为辅助受体。一些病毒可以使用CCR 5和CXCR 4两者用于病毒进入（即，是双嗜性的），而其它趋化因子受体可被病毒株的子集使用。由于HIV-1、HIV-2和猿猴免疫缺陷病毒（SIV）的遗传多样性以及除CCR 5或CXCR 4以外的趋化因子受体影响病毒发病机制的潜力，我们测试了一组28种HIV-1、HIV-2和SIV包膜（Env）蛋白利用趋化因子受体、孤儿受体、和疱疹病毒编码的趋化因子受体同源物。虽然所有Env蛋白使用CCR 5或CXCR 4或两者，但也有几种使用CCR 3。CCR 3的使用强烈依赖于其表面表达水平，大量的病毒Env蛋白能够在较高的表面表达水平下利用这种辅助受体。ChemR 1是一种孤儿受体，最近显示与CC趋化因子I309（因此更名为CCR 8）结合，在单核细胞和淋巴细胞群中表达，并作为多种HIV-1、HIV-2和SIV Env蛋白的辅助受体发挥作用。SIV毒株对ChemR 1/CCR 8的使用部分依赖于V3环序列。孤儿受体V28支持Env介导的细胞-细胞融合的四个T-或双嗜性HIV-1和HIV-2株。另外三种孤儿受体对测试的28种Env蛋白中的任何一种都不起作用。同样，疱疹病毒编码的六个七跨膜结构域受体中有五个不支持Env介导的膜融合。然而，由巨细胞病毒编码的趋化因子受体US 28确实支持两种HIV-1毒株的无效感染。这些发现表明，其他趋化因子受体可以作为HIV和SIV辅助受体，表面表达水平可以强烈影响辅助受体的使用。
Human immunodeficiency virus type 1 (HIV-1) requires both CD4 and a coreceptor to infect cells. Macrophage-tropic (M-tropic) HIV-1 strains utilize the chemokine receptor CCR5 in conjunction with CD4 to infect cells, while T-cell-tropic (T-tropic) strains generally utilize CXCR4 as a coreceptor. Some viruses can use both CCR5 and CXCR4 for virus entry (i.e., are dual-tropic), while other chemokine receptors can be used by a subset of virus strains. Due to the genetic diversity of HIV-1, HIV-2, and simian immunodeficiency virus (SIV) and the potential for chemokine receptors other than CCR5 or CXCR4 to influence viral pathogenesis, we tested a panel of 28 HIV-1, HIV-2, and SIV envelope (Env) proteins for the ability to utilize chemokine receptors, orphan receptors, and herpesvirus-encoded chemokine receptor homologs by membrane fusion and virus infection assays. While all Env proteins used either CCR5 or CXCR4 or both, several also used CCR3. Use of CCR3 was strongly dependent on its surface expression levels, with a larger number of viral Env proteins being able to utilize this coreceptor at the higher levels of surface expression. ChemR1, an orphan receptor recently shown to bind the CC chemokine I309 (and therefore renamed CCR8), was expressed in monocyte and lymphocyte cell populations and functioned as a coreceptor for diverse HIV-1, HIV-2, and SIV Env proteins. Use of ChemR1/CCR8 by SIV strains was dependent in part on V3 loop sequences. The orphan receptor V28 supported Env-mediated cell-cell fusion by four T- or dual-tropic HIV-1 and HIV-2 strains. Three additional orphan receptors failed to function for any of the 28 Env proteins tested. Likewise, five of six seven-transmembrane-domain receptors encoded by herpesviruses did not support Env-mediated membrane fusion. However, the chemokine receptor US28, encoded by cytomegalovirus, did support inefficient infection by two HIV-1 strains. These findings indicate that additional chemokine receptors can function as HIV and SIV coreceptors and that surface expression levels can strongly influence coreceptor use.