INSERM U941, Paris 75010, France.
Retrovirology. 2013 May 6;10:50. doi: 10.1186/1742-4690-10-50.
HIV-2, which was transmitted to humans from a distant primate species (sooty mangabey), differs remarkably from HIV-1 in its infectivity, transmissibility and pathogenicity. We have tested the possibility that a greater susceptibility of HIV-2 capsid (CA) to the human restriction factor TRIM5α (hTRIM5α) could contribute to these differences.
We constructed recombinant clones expressing CA from a variety of HIV-2 viruses in the context of HIV-1 NL4-3-luciferase. CA sequences were amplified from the plasma of HIV-2 infected patients, including 8 subtype A and 7 subtype B viruses. CA from 6 non-epidemic HIV-2 subtypes, 3 HIV-2 CRF01_AB recombinants and 4 SIVsmm viruses were also tested. Susceptibility to hTRIM5α was measured by comparing single-cycle infectivity in human target cells expressing hTRIM5α to that measured in cells in which hTRIM5α activity was inhibited by overexpression of hTRIM5γ.The insertion of HIV-2 CA sequences in the context of HIV-1 did not affect expression and maturation of the HIV-2 CA protein. The level of susceptibility hTRIM5α expressed by viruses carrying HIV-2 CA sequences was up to 9-fold higher than that of HIV-1 NL4-3 and markedly higher than a panel of primary HIV-1 CA sequences. This phenotype was found both for viruses carrying CA from primary HIV-2 sequences and viruses carrying CA from laboratory-adapted HIV-2 clones. High hTRIM5α susceptibility was found in all HIV-2 subtypes. In this series of viruses, susceptibility to hTRIM5α was not significantly affected by the presence of a proline at position 119 or by the number of prolines at positions 119, 159 or 178 in HIV-2 CA. No significant correlation was found between HIV-2 viremia and sensitivity to hTRIM5α.
HIV-2 capsid sequences expressed high levels of susceptibility to hTRIM5α. This property, common to all HIV-2 sequences tested, may contribute in part to the lower replication and pathogenicity of this virus in humans.
HIV-2 是从一种遥远的灵长类动物（黑眉长尾猴）传播给人类的，其感染性、传染性和致病性与 HIV-1 有显著差异。我们已经测试了 HIV-2 衣壳（CA）对人类限制因子 TRIM5α（hTRIM5α）的易感性增加的可能性，这可能导致了这些差异。
我们构建了表达来自各种 HIV-2 病毒的 CA 的重组克隆，这些病毒的 CA 序列是从 HIV-2 感染患者的血浆中扩增出来的，包括 8 种亚型 A 和 7 种亚型 B 病毒。还测试了来自 6 种非流行 HIV-2 亚型、3 种 HIV-2 CRF01_AB 重组体和 4 种 SIVsmm 病毒的 CA。通过比较在表达 hTRIM5α 的人类靶细胞中单次感染循环的感染性与在 hTRIM5α 活性被 hTRIM5γ 过表达抑制的细胞中测量的感染性，来测量对 hTRIM5α 的敏感性。在 HIV-1 背景下插入 HIV-2 CA 序列不会影响 HIV-2 CA 蛋白的表达和成熟。携带 HIV-2 CA 序列的病毒表达的 hTRIM5α 的敏感性水平比 HIV-1 NL4-3 高 9 倍，比一组原发性 HIV-1 CA 序列高得多。这种表型既存在于携带原发性 HIV-2 CA 序列的病毒中，也存在于携带实验室适应的 HIV-2 克隆 CA 的病毒中。在所有 HIV-2 亚型中都发现了高 hTRIM5α 易感性。在这一系列病毒中，HIV-2 CA 第 119 位脯氨酸的存在或第 119、159 或 178 位脯氨酸的数量对 hTRIM5α 的敏感性没有显著影响。在 HIV-2 病毒血症与对 hTRIM5α 的敏感性之间没有发现显著相关性。
HIV-2 衣壳序列对 hTRIM5α 表达高水平的易感性。这种特性在所有测试的 HIV-2 序列中都很常见，可能部分导致了这种病毒在人类中的复制和致病性较低。
