The inhibition of CD1d-mediated antigen presentation upon an HSV-1 infection is VP22-dependent (VIR1P.1134)

Abstract

Abstract CD1d-restricted T (NKT) cells are important for controlling a herpes simplex virus (HSV) infection. One of the mechanisms of immune evasion by HSV is to down-regulate CD1d-mediated activation of NKT cells. VP22 is an HSV-1-encoded protein responsible for reorganizing the host cell’s cytoskeletal network and viral spreading. We have shown that modification of the cytoskeleton can alter CD1d-mediated antigen presentation. In this study, we found an HSV-1 lacking VP22 (ΔUL49) was impaired in its ability to inhibit CD1d-mediated antigen presentation compared to wild-type (WT) virus; this was reversed by a repair virus (UL49R) in CD1d-expressing cells. Of importance, the effects of VP22 were shown to be exerted on the T322/S323 dyad, critical residues for the virus to reduced antigen presentation. We further demonstrated that CD1d recycling was inhibited by infection with WT and UL49R, but not ΔUL49 virus. Rather than inhibiting antigen presentation by CD1d, ectopic expression of VP22 in CD1d-expressing cells complemented the VP22-deficient virus in inhibiting antigen presentation. Therefore, VP22 is required (but not sufficient) for the inhibition of CD1d-mediated antigen presentation by an HSV-1 infection.