Fusion Stage of HIV-1 Entry Depends on Virus-Induced Cell Surface Exposure of Phosphatidylserine

Publication date: 12 July 2017
Source:Cell Host & Microbe, Volume 22, Issue 1
Author(s): Elena Zaitseva, Eugene Zaitsev, Kamran Melikov, Anush Arakelyan, Mariana Marin, Rafael Villasmil, Leonid B. Margolis, Gregory B. Melikyan, Leonid V. Chernomordik
HIV-1 entry into host cells starts with interactions between the viral envelope glycoprotein (Env) and cellular CD4 receptors and coreceptors. Previous work has suggested that efficient HIV entry also depends on intracellular signaling, but this remains controversial. Here we report that formation of the pre-fusion Env-CD4-coreceptor complexes triggers non-apoptotic cell surface exposure of the membrane lipid phosphatidylserine (PS). HIV-1-induced PS redistribution depends on Ca²⁺ signaling triggered by Env-coreceptor interactions and involves the lipid scramblase TMEM16F. Externalized PS strongly promotes Env-mediated membrane fusion and HIV-1 infection. Blocking externalized PS or suppressing TMEM16F inhibited Env-mediated fusion. Exogenously added PS promoted fusion, with fusion dependence on PS being especially strong for cells with low surface density of coreceptors. These findings suggest that cell-surface PS acts as an important cofactor that promotes the fusogenic restructuring of pre-fusion complexes and likely focuses the infection on cells conducive to PS signaling.

Graphical abstract

Teaser

Zaitseva et al. show that HIV binding to target cells induces signaling that leads to exposure of phosphatidylserine on the cell surface. Interaction between the viral envelope glycoprotein and phosphatidylserine facilitates receptor-dependent merger of viral and cell membranes and infection. Phosphatidylserine dependence may focus infection on cells of certain activation status.


http://ift.tt/2ugdRsC