Lin Tsai-Yu, Emerman Michael
Pathobiology Graduate Program, University of Washington, Seattle, WA 98195, USA.
Retrovirology. 2006 Oct 12;3:70. doi: 10.1186/1742-4690-3-70.
The capsid (CA) protein of HIV-1 binds with high affinity to the host protein cyclophilin A (CypA). This binding positively affects some early stage of the viral life-cycle because prevention of binding either by drugs that occupy that active site of cyclophilin A, by mutation in HIV-1 CA, or RNAi that knocks down intracellular CypA level diminishes viral infectivity. The closely related lentivirus, SIVcpz also binds CypA, but it was thought that this interaction was limited to the HIV-1/SIVcpz lineage because other retroviruses failed to interact with CypA in a yeast two-hybrid assay.
We find that diverse lentiviruses, FIV and SIVagmTAN also bind to CypA. Mutagenesis of FIV CA showed that an amino acid that is in a homologous position to the proline at amino acid 90 of HIV-1 CA is essential for FIV interactions with CypA.
These results demonstrate that CypA binding to lentiviruses is more widespread than previously thought and suggest that this interaction is evolutionarily important for lentiviral infection.
HIV-1的衣壳（CA）蛋白与宿主蛋白亲环素A（CypA）具有高亲和力结合。这种结合对病毒生命周期的某些早期阶段有积极影响，因为通过占据亲环素A活性位点的药物、HIV-1 CA中的突变或降低细胞内CypA水平的RNA干扰来阻止结合，都会降低病毒感染性。密切相关的慢病毒SIVcpz也结合CypA，但人们认为这种相互作用仅限于HIV-1/SIVcpz谱系，因为在酵母双杂交试验中其他逆转录病毒未能与CypA相互作用。
我们发现多种慢病毒、猫免疫缺陷病毒（FIV）和非洲绿猴SIV（SIVagmTAN）也与CypA结合。FIV CA的诱变表明，与HIV-1 CA第90位氨基酸处的脯氨酸处于同源位置的一个氨基酸对于FIV与CypA的相互作用至关重要。
这些结果表明，CypA与慢病毒的结合比以前认为的更为广泛，并且表明这种相互作用在慢病毒感染的进化过程中很重要。
