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) causesdown-regulation of cell surface expression of MHCclass I. The present invention is directed to a mutant with a 9-kb deletion inthe S component of the HCMV genome (including openreading frames IRS1-US9 and US11) which fails to down-regulate class I heavychains. By examining the phenotypes of mutants withsmaller deletions with this portion of the HCMV genome, a 7-kb regioncontaining at least 9 open reading frames was shown to contain thegenes required for reduction in heavy chain expression. Furthermore, it wasdetermined that two subregions (A and B) of the 7-kb regioneach 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 isintracytoplasmic, similar to the adenovirus type 2 E3-19K glycoproteinwhich inhibits surface expression of class I heavy chains.