Varicella-zoster virus retains major histocompatibility complex class I proteins in the Golgi compartment of infected cells

We sought to examine the effects of varicella-zoster virus (VZV) infection on the expression of major histocompatibility complex class I (MHC I) molec ules by human fibroblasts and T lymphocytes. By flow cytometry, VZV infecti on reduced the cell surface expression of MHC I molecules on fibroblasts si gnificantly, yet the expression of transferrin receptor was not affected. I mportantly, when human fetal thymus/liver implants in SCID-hu mice were ino culated with VZV, cell surface MHC I expression was downregulated specifica lly on VZV-infected human CD3(+) T lymphocytes, a prominent target that sus tains VZV viremia, The stage in the MHC I assembly process that was disrupt ed by VZV in fibroblasts was examined in pulse-chase and immunoprecipitatio n experiments in the presence of endoglycosidase H. MNC I complexes continu ed to be assembled in VZV-infected cells and were not retained in the endop lasmic reticulum, In contrast, immunofluorescence and confocal microscopy s howed that VZV infection resulted in an accumulation of MHC I molecules whi ch colocalized to the Golgi compartment. Inhibition of late viral gene expr ession by treatment of infected fibroblasts with phosphonoacetic acid did n ot influence the modulation of MHC I expression, nor did transfection of ce lls with plasmids expressing immediate early viral proteins. However, cells transfected with a plasmid carrying the early gene ORF66 did result in a s ignificant downregulation of MHC I expression, suggesting that this gene en codes a protein with an immunomodulatory function, Thus, VZV downregulates MHC I expression by impairing the transport of MHC I molecules from the Gol gi compartment to the cell surface; this effect may enable the virus to eva de CD8(+) T-cell immune recognition during VZV pathogenesis, including the critical phase of T-lymphocyte-associated viremia.