Specht Anke, DeGottardi M Quinn, Schindler Michael, Hahn Beatrice, Evans David T, Kirchhoff Frank
Institute of Virology, Universitätsklinikum, 89081 Ulm, Germany.
Virology. 2008 Mar 30;373(1):229-37. doi: 10.1016/j.virol.2007.11.019. Epub 2007 Dec 21.
It has been demonstrated that the HIV-1 NL4-3 and IIIB Nef alleles downregulate HLA-A and -B but not -C or -E from the cell surface. It remained elusive, however, whether selective modulation of specific HLA molecules is conserved between different groups of human and simian immunodeficiency viruses, respectively. To address this, we analyzed a large panel of primate lentiviral Nef proteins and we found that this property is conserved among nef alleles from the M, N and O groups of HIV-1, as well as those from SIVcpz, the precursor of HIV-1, and a variety of other highly divergent primate lentiviruses. In conclusion, our data indicate that Nef's ability to selectively downregulate HLA-A and -B alleles to prevent CTL lysis and NK killing of virally infected cells is conserved among different primate lentiviral lineages and preceded the zoonotic transmission of SIVcpz from chimpanzees to humans.
已证明，HIV-1 NL4-3和IIIB Nef等位基因可从细胞表面下调HLA-A和-B，但不会下调HLA-C或-HLA-E。然而，不同组的人类免疫缺陷病毒和猿猴免疫缺陷病毒之间是否分别保守特定HLA分子的选择性调节仍不清楚。为了解决这个问题，我们分析了大量灵长类慢病毒Nef蛋白，发现这种特性在HIV-1的M、N和O组的Nef等位基因中是保守的，HIV-1的前体SIVcpz以及其他多种高度分化的灵长类慢病毒的Nef等位基因中也是保守的。总之，我们的数据表明，Nef选择性下调HLA-A和-B等位基因以防止CTL裂解和NK杀伤病毒感染细胞的能力在不同的灵长类慢病毒谱系中是保守的，并且在SIVcpz从黑猩猩到人类的人畜共患传播之前就已存在。
