Sphingomyelin Synthase 2, but not Sphingomyelin Synthase 1, is Involved in HIV-1 Envelope-mediated Membrane Fusion [Membrane Biology]

September 17th, 2014 by Hayashi, Y., Nemoto-Sasaki, Y., Tanikawa, T., Oka, S., Tsuchiya, K., Zama, K., Mitsutake, S., Sugiura, T., Yamashita, A.

Membrane fusion between the viral envelope and plasma membranes of target cells has previously been correlated with HIV-1 infection. Lipids in the plasma membrane, including sphingomyelin (SM), may be crucially involved in HIV-1 infection; however, the role of lipid-metabolic enzymes in membrane fusion remains unclear. In the present study, we examined the roles of SM synthase (SMS) in HIV-1 Env-mediated membrane fusion using a cell-cell fusion assay with HIV-1 mimetics and their target cells. We employed reconstituted cells as target cells that stably express SMS1 or SMS2 in SMS-deficient cells. Fusion susceptibility was approximately five-fold higher in SMS2-expressing cells (not in SMS1-expressing cells) than in SMS-deficient cells. The enhancement of fusion susceptibility observed in SMS2-expressing cells was reversed and reduced by SMS2 knockdown. We also found that catalytically non-active SMS2 promoted membrane fusion susceptibility. Moreover, SMS2 co-localized and was constitutively associated with the HIV receptor/co-receptor complex in the plasma membrane. In addition, HIV-1 Env treatment resulted in a transient increase in nonreceptor tyrosine kinase (Pyk2) phosphorylation in SMS2- and catalytically non-active SMS2-expressing cells. We observed that F-actin polymerization in the region of membrane fusion was more prominent in SMS2-expressing cells than SMS-deficient cells. Taken together, our research provides insight into a novel function of SMS2: regulation of HIV-1 Env-mediated membrane fusion via actin rearrangement.