Serinc Inhibits Hiv-1 Env Induced Membrane Fusion And Slows Fusion Pore Enlargement

The SERINC family of proteins are integral membrane proteins that regulate the incorporation of serine into phospholipids, to create PS, and into sphingolipids. It has recently been shown that two members of the family, SERINC3 and SERINC5, inhibit HIV infectivity. Using a cell-cell fusion system to determine the extent to which inhibition of infectivity is due to reduced fusion, we found that the presence of SERINC3 or SERINC5 in either effector or target cells slows the kinetics and reduces the extent of fusion induced by HIV-1 Env. These two incorporators of serine greatly retard fusion pore enlargement, as determined by the rate of aqueous dye transfer once a pore forms. Nef is an auxiliary protein of HIV that is well-known to enhance HIV infectivity. The presence of SERINC5 and Nef in effector cells leads to the same extent of fusion induced by expression of Env alone, showing that Nef eliminates the reduction of fusion caused by SERINC. (R01 GM 101 539).