Herpes simplex virus evades natural killer T cell recognition by suppressing CD1d recycling.

Natural killer T cells, which are stimulated by lipids presented by CD1d molecules, are crucial in antiviral host defense. How viruses evade natural killer T cell recognition remains unclear. Here we show that infection with herpes simplex virus type 1 (HSV-1) reduced CD1d surface expression on antigen-presenting cells. HSV-1 did not inhibit CD1d protein synthesis or enhance constitutive CD1d endocytosis. Instead, HSV-1 prevented the reappearance of endocytosed CD1d on the cell surface by redistributing endocytosed CD1d to the lysosome limiting membrane. HSV-1 might also inhibit the transport of newly synthesized CD1d to the cell surface. Such inhibition of CD1d surface expression impaired antigen-presenting cell-mediated stimulation of natural killer T cells, supporting the idea that this mechanism may be an important HSV-1 immune evasion strategy.