Pushkarsky T, Zybarth G, Dubrovsky L, Yurchenko V, Tang H, Guo H, Toole B, Sherry B, Bukrinsky M
The Picower Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA.
Proc Natl Acad Sci U S A. 2001 May 22;98(11):6360-5. doi: 10.1073/pnas.111583198. Epub 2001 May 15.
Cyclophilin A (CyPA) is specifically incorporated into the virions of HIV-1 and has been shown to enhance significantly an early step of cellular HIV-1 infection. Our preliminary studies implicated CD147 as a receptor for extracellular CyPA. Here, we demonstrate a role for CyPA-CD147 interaction during the early steps of HIV-1 infection. Expression of human CD147 increased infection by HIV-1 under one-cycle conditions. However, susceptibility to infection by viruses lacking CyPA (simian immunodeficiency virus or HIV-1 produced in the presence of cyclosporin A) was unaffected by CD147. Virus-associated CyPA coimmunoprecipitated with CD147 from infected cells. Antibody to CD147 inhibited HIV-1 entry as evidenced by the delay in translocation of the HIV-1 core proteins from the membrane and inhibition of viral reverse transcription. Viruses whose replication did not require CyPA (SIV or mutant HIV-1) were resistant to the inhibitory effect of anti-CD147 antibody. These results suggest that HIV-1 entry depends on an interaction between virus-associated CyPA and CD147 on a target cell.
亲环素A（CyPA）特异性地整合到HIV-1病毒体中，并已证明能显著增强细胞HIV-1感染的早期步骤。我们的初步研究表明CD147是细胞外CyPA的受体。在此，我们证明了CyPA-CD147相互作用在HIV-1感染早期步骤中的作用。在单周期条件下，人CD147的表达增加了HIV-1的感染。然而，缺乏CyPA的病毒（猿猴免疫缺陷病毒或在环孢菌素A存在下产生的HIV-1）的感染易感性不受CD147的影响。病毒相关的CyPA与感染细胞中的CD147共免疫沉淀。抗CD147抗体抑制HIV-1进入，这可通过HIV-1核心蛋白从膜上的转运延迟和病毒逆转录的抑制来证明。复制不需要CyPA的病毒（SIV或突变型HIV-1）对抗CD147抗体的抑制作用具有抗性。这些结果表明，HIV-1进入取决于病毒相关的CyPA与靶细胞上的CD147之间的相互作用。
