A VP22-Null HSV-1 Is Impaired in Inhibiting CD1d-Mediated Antigen Presentation.
CD1d-restricted T (natural killer T [NKT]) cells are important for controlling a herpes simplex virus (HSV) infection. One of the mechanisms of immune evasion by HSV is to downregulate 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 previously shown that modification of the cytoskeleton can alter CD1d-mediated antigen presentation. In this study, we found that an HSV-1 lacking VP22 (ΔUL49) was impaired in its ability to inhibit CD1d-mediated antigen presentation compared with the wild-type (WT) virus; this was reversed by a repair virus (UL49R) in CD1d-expressing cells. We further demonstrated that CD1d recycling was inhibited by infection with WT and UL49R, but not the ΔUL49 virus. Ectopic expression of VP22 in CD1d-expressing cells complemented the VP22-deficient virus in inhibiting antigen presentation. Moreover, inhibiting viral protein synthesis rescued VP22-dependent inhibition of CD1d antigen presentation. In conclusion, our findings suggest that VP22 is required (but not sufficient) for the inhibition of CD1d-mediated antigen presentation by an HSV-1 infection.
1 Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, Indiana.
Jianyun
J
Liu
1 Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, Indiana.
Richard M
RM
Gallo
2 Department of Biological Sciences, University of Alabama , Tuscaloosa, Alabama.
Carol
C
Duffy
1 Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, Indiana.
Randy R
RR
Brutkiewicz
D017951:Antigen Presentation; D055610:Antigens, CD1d / Q000378:metabolism*; D057809:HEK293 Cells; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007108:Immune Tolerance; D055611:Natural Killer T-Cells / Q000276:immunology*; D015678:Viral Structural Proteins / Q000172:deficiency / Q000378:metabolism*
D055610:Antigens, CD1d; C526877:CD1D protein, human; D015678:Viral Structural Proteins; C073413:herpes simplex virus type 1 protein VP22