Ryzhova Elena V, Vos Robin M, Albright Andrew V, Harrist Alexia V, Harvey Thomas, González-Scarano Francisco
Department of Neurology and Microbiology, University of Pennsylvania, 3 W. Gates, 3400 Spruce Street, Philadelphia, Pennsylvania 19104-4283, USA.
J Virol. 2006 Mar;80(6):2694-704. doi: 10.1128/JVI.80.6.2694-2704.2006.
Human immunodeficiency virus (HIV) replication in the major natural target cells, CD4+ T lymphocytes and macrophages, is parallel in many aspects of the virus life cycle. However, it differs as to viral assembly and budding, which take place on plasma membranes in T cells and on endosomal membranes in macrophages. It has been postulated that cell type-specific host factors may aid in directing viral assembly to distinct destinations. In this study we defined annexin 2 (Anx2) as a novel HIV Gag binding partner in macrophages. Anx2-Gag binding was confined to productively infected macrophages and was not detected in quiescently infected monocyte-derived macrophages (MDM) in which an HIV replication block was mapped to the late stages of the viral life cycle (A. V. Albright, R. M. Vos, and F. Gonzalez-Scarano, Virology 325:328-339, 2004). We demonstrate that the Anx2-Gag interaction likely occurs at the limiting membranes of late endosomes/multivesicular bodies and that Anx2 depletion is associated with a significant decline in the infectivity of released virions; this coincided with incomplete Gag processing and inefficient incorporation of CD63. Cumulatively, our data suggest that Anx2 is essential for the proper assembly of HIV in MDM.
人类免疫缺陷病毒（HIV）在主要天然靶细胞，即CD4 + T淋巴细胞和巨噬细胞中的复制，在病毒生命周期的许多方面是并行的。然而，在病毒组装和出芽方面存在差异，这分别发生在T细胞的质膜上和巨噬细胞的内体膜上。据推测，细胞类型特异性宿主因子可能有助于将病毒组装引导至不同的目的地。在本研究中，我们将膜联蛋白2（Anx2）定义为巨噬细胞中一种新的HIV Gag结合伴侣。Anx2与Gag的结合仅限于高效感染的巨噬细胞，而在静止感染的单核细胞衍生巨噬细胞（MDM）中未检测到，在这些细胞中，HIV复制阻滞被定位到病毒生命周期的后期（A. V. Albright、R. M. Vos和F. Gonzalez-Scarano，《病毒学》325:328 - 339，2004）。我们证明Anx2与Gag的相互作用可能发生在晚期内体/多囊泡体的限制膜上，并且Anx2的缺失与释放病毒颗粒的感染性显著下降有关；这与Gag加工不完全和CD63掺入效率低下相一致。总的来说，我们的数据表明Anx2对于MDM中HIV的正确组装至关重要。
