Multiple independent loci within the human cytomegalovirus unique short region down-regulate expression of major histocompatibility complex class I heavy chains.
Reduction of major histocompatibility complex class I cell surface expression occurs in adenovirus-, herpes simplex virus-, human cytomegalovirus (HCMV)-, and murine cytomegalovirus-infected cell systems. Recently, it was demonstrated that the down-regulation mediated by HCMV infection is posttranslational, as a result of increased turnover of class I heavy chains in the endoplasmic reticulum (M. F. C. Beersma, M. J. E. Bijlmakers, and H. L. Ploegh, J. Immunol. 151:4455-4464, 1993; Y. Yamashita, K. Shimokata, S. Saga, S. Mizuno, T. Tsurumi, and Y. Nishiyama, J. Virol. 68:7933-7943, 1994. To identify HCMV genes involved in class I regulation, we screened our bank of HCMV deletion mutants for this phenotype. A mutant with a 9-kb deletion in the S component of the HCMV genome (including open reading frames IRS1 to US9 and US11) failed to down-regulate class I heavy chains. By examining the effects of smaller deletions within this portion of the HCMV genome, a 7-kb region containing at least nine open reading frames was shown to contain the genes required for reduction in heavy-chain expression. Furthermore, it was determined that at least two independent loci within the 7-kb region were able to cause class I heavy-chain down-regulation. One of these, US11, encodes a 32-kDa glycoprotein which causes down-regulation of class I heavy chains in the absence of other viral gene products. Hence, a specific function associated with a phenotype of the HCMV replicative cycle has been mapped to a dispensable gene region. These loci may be important for evasion of the host's immune response and viral persistence.
Jones
T R
TR
Molecular Biology Section, American Cyanamid Co., Pearl River, New York 10965, USA.
Hanson
L K
LK
Sun
L
L
Slater
J S
JS
Stenberg
R M
RM
Campbell
A E
AE
D001254:Astrocytoma / Q000821:virology; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics*; D015536:Down-Regulation; D005347:Fibroblasts / Q000821:virology; D015967:Gene Expression Regulation, Viral; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D017384:Sequence Deletion; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I