HIV Enters Cells via Endocytosis and Dynamin-Dependent Fusion with Endosome

Kosuke Miyauchi, Yuri Kim, Olga Latinovic, Vladimir Morozov, and Gregory B. Melikyan

Cell 2009, Vol.137, 433-444

Speaker：Siao-Fen Yeh(葉曉芬)                   Time：15:00~16:00, Dec.30,2009

Commentator：Dr. Shun-Hua Chen(陳舜華 老師)    Place：Room 601

Abstract：

   Human immunodeficiency virus（HIV）is an enveloped lentivirus. Previous study says that acidification of endosome is an obligatory entry for enveloped virus to enter cells and release its capsid. But some studies in 2002, 2004, and 2005, indicating that HIV infects cells independent of acidification. So well-known pathway is that HIV binds to CD4 and coreceptors of the target cells, such as CD4+ T cells and macrophages. Otherwise, some studies shows that HIV particles can be observed in the intracellular vesicles. Summarizing anterior researches, authors set up the hypothesis of HIV alternative entry. To discovery another entry of HIV, they design TZM-bl cells(cell surface expressing CD4, CCR5 and CXCR4) and two pseudovirus with particular envelope : JRFL with CCR5 tropism and HXB2 with CXCR4 tropism. First, they using β-lactamase(BlaM) assay to measure actual viral content amount in cytoplasma. The result indicates that plasma membrane fusion is not only entry for HIV. To confirm another pathway is endocytosis, authors used a technique called single-virus imaging which can observe the trend of HIV in the cell. In this experiment, they discover there are two kinds of endocytosis, and there are three routes for HIV enter to cells. Then, they were sure that endocytosis are entry for HIV , they wanted to know much clear mechanism of endocytosis in HIV infection. One research showed that inhibition of clathrin-mediated endocytosis reduced HIV-cell fusion. So authors chose dynamin inhibitor to discover it. Finally, authors conclude that dynamin-dependent endocytosis is a productive entry for HIV.

References：

1.          Pradeep D. Uchil and Walther Mothes, 2009. HIV Entry Revisited. Cell 137, 402-404

2.          Robert W. Doms and Ddier Trono, 2001. The plasma membrane as a combat zone in the HIV battlefield. Gene & Development 14: 2677-2688

3.          Jessica Daecke, Oliver T. Fackler, Matthias T. Dittmar , and Hans-Georg Kräusslich, 2004. Journal of Virology , Vol.79 , 1581-1594