HSV-1 UL56 protein recruits cellular NEDD4-family ubiquitin ligases to suppress CD1d expression and NKT cell function.

ABSTRACT: Herpesviruses, including α-herpesvirus and herpes simplex virus (HSV-1), are masters of immune evasion. Previously we demonstrated that CD1d-restricted NKT cells are required for optimal anti-HSV-1 immune responses and HSV-1 efficiently downregulates CD1d to suppress NKT cell function. To delineate how the virus evades NKT cell function and establishes infection in vivo, we screened an HSV-1 expression library to identify the viral gene(s) downregulating CD1d and discovered that a leaky late gene, UL56, most efficiently suppresses CD1d expression by degrading the protein, apparently via both proteasome- and lysosome-dependent pathways. To investigate the molecular mechanism of UL56 suppression of CD1d expression, we purified and identified UL56-associated proteins by mass spectromet

SUBMITTER: Qiu L 

PROVIDER: S-EPMC11998485 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature