HUMAN CYTOMEGALOVIRUS-INFECTION DOWN-REGULATES EXPRESSION OF THE CELLULAR AMINOPEPTIDASES CD10 AND CD13

During the course of a productive infection, human cytomegalovirus (HC MV) has a sophisticated relationship with its host cell. An increasing number of virus-encoded genes are being identified which act specific ally to usurp or modulate functions in the host cell associated with t ranscriptional control, cell signalling, and protein synthesis. While HCMV infection is associated with a general upregulation of cellular g ene expression, the expression a small subset of cellular proteins, in cluding the MHC-I heavy chain and fibronectin, is downregutated. This study now identifies two additional cellular proteins, aminopeptidase N (CD13) and neutral endopeptidase (CD10), that are downregulaled duri ng HCMV infection. While aminopeptidase N and neutral endopeptidase ex hibit no significant sequence homology, both are expressed on the cell surface and have very similar enzymatic properties. HCMV infection wa s associated with reduced surface expression and enzyme activity of GD 13 and CD10, an apparent decrease in the rate of synthesis of both pro teins in metabolic-labelling experiments, and inhibited glycosylation of the nascent CD13 and CD10 polypeptide chains that were synthesized. Levels of CD10 poly A(+) RNA were suppressed efficiently at all stage s of virus infection; however, the reduction in CD13 poly A(+) RNA lev els was much less pronounced. This differential effect suggests that H CMV may be downregulating expression of CD10 and CD13 by independent m echanisms. Indeed, treatment of cells with an inhibitor of viral DNA s ynthesis blocks downregulation of CD13, whilst downregulation of CD10 is unaffected. White it is not yet clear what advantage is bestowed on the virus by downregulating expression of CD13 and CD10, aminopeptida ses are known to have a role in peptide processing in both the MHC cla ss I the MHC class II antigen presentation pathways, (C) 1998 Academic Press