IDENTIFICATION OF A HUMAN CYTOMEGALOVIRUS GENE REGION INVOLVED IN DOWN-REGULATION OF MHC CLASS I HEAVY CHAIN EXPRESSION.

摘要

Infection of human fibroblast cells with human cytomegalovirus (HCMV) causes down-regulation of cell surface expression of MHC class I. The present invention is directed to a mutant with a 9-kb deletion in the S component of the HCMV genome (including open reading frames IRS1-US9 and US11) which fails to down-regulate class I heavy chains. By examining the phenotypes of mutants with smaller deletions with this portion of the HCMV genome, a 7-kb region containing at least 9 open reading frames was shown to contain the genes required for reduction in heavy chain expression. Furthermore, it was determined that two subregions (A and B) of the 7-kb region each contained genes which were sufficient to cause heavy chain down-regulation. In subregion B, the US11 gene product is involved. It encodes an endoglycosidase H-sensitive glycoprotein which is intracytoplasmic, similar to the adenovirus type 2 E3-19K glycoprotein which inhibits surface expression of class I heavy chains.