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Journal of Virology, September 2000, p. 8028-8037, Vol. 74, No. 17
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Role of Human Cytomegalovirus Immediate-Early Proteins in Cell Growth Control

Jonathan P. Castillo,1 Andrew D. Yurochko,2 and Timothy F. Kowalik1,3,*

Program in Immunology and Virology1 and Department of Molecular Genetics and Microbiology,3 University of Massachusetts Medical School, Worcester, Massachusetts 01655, and Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 711302

Received 6 January 2000/Accepted 3 June 2000

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that has been implicated in several disorders, including an association between HCMV reactivation and the overproliferation of arterial smooth muscle cells observed in restenosis. Although HCMV can mediate a growth-arrest phenotype in infected cells, the virus can also promote an environment conducive to proliferation. Here, we present evidence that the HCMV immediate-early (IE) proteins, IE1-72 and IE2-86, may be responsible for inducing this proliferative environment by altering cell cycle control. We find that expression of either of these IE proteins can alter the cell cycle distribution of randomly cycling cells towards S and G2/M phases. Additionally, we find that expression of IE2-86, but not IE1-72, induces quiescent cells into S phase and delays cell cycle exit. In the absence of p53, IE1-72 expression can induce S phase and delay cell cycle exit. We also demonstrate that p53 protein levels increase in fibroblasts following the expression of IE1-72. The observed accumulation of p53 protein in IE1-72-expressing cells may account for the inability of IE1-72 to induce S phase and delay cell cycle exit. Our data suggest that expression of HCMV IE1-72 and IE2-86 is sufficient to alter the cell cycle to generate an environment conducive to proliferation.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, University of Massachusetts, 55 Lake Ave. North, Worcester, MA 01655. Phone: (508) 856-6035. Fax: (508) 856-5920. E-mail: Timothy.Kowalik{at}umassmed.edu.

Journal of Virology, September 2000, p. 8028-8037, Vol. 74, No. 17
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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