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PMID: 11711622 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Altered cellular mRNA levels in human cytomegalovirus-infected fibroblasts: viral block to the accumulation of antiviral mRNAs.

Journal of virology ·Vol. 75 ·No. 24 ·2001-12-00 ·Pages 12319-30

Browne EP, Wing B, Coleman D, Shenk T

Abstract

The effect of human cytomegalovirus (HCMV) infection on cellular mRNA accumulation was analyzed by gene chip technology. During a 48-h time course after infection of human diploid fibroblasts, 1,425 cellular mRNAs were found to be up-regulated or down-regulated by threefold or greater in at least two consecutive time points. Several classes of genes were prominently affected, including interferon response genes, cell cycle regulators, apoptosis regulators, inflammatory pathway genes, and immune regulators. The number of mRNAs that were up-regulated or down-regulated were roughly equal over the complete time course. However, for the first 8 h after infection, the number of up-regulated mRNAs was significantly less than the number of down-regulated mRNAs. By analyzing the mRNA expression profile of cells infected in the presence of cycloheximide, it was found that a minimum of 25 mRNAs were modulated by HCMV in the absence of protein synthesis. These included mRNAs encoded by a small number of interferon-responsive genes, as well as beta interferon itself. Cellular mRNA levels in cytomegalovirus-infected cells were compared to the levels in cells infected with UV-inactivated virus. The inactivated virus caused the up-regulation of a much greater number of mRNAs, many of which encoded proteins with antiviral roles, such as interferon-responsive genes and proinflammatory cytokines. These data argue that one or more newly synthesized viral gene products block the induction of antiviral pathways that are triggered by HCMV binding and entry.

MeSH Terms
Apoptosis Cells, Cultured Cytokines/genetics Cytomegalovirus/physiology,radiation effects Fibroblasts/metabolism,virology Humans Protein Biosynthesis RNA, Messenger/analysis,metabolism Ultraviolet Rays
Chemicals
Cytokines RNA, Messenger
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Browne E P
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014, USA.
Wing B
Coleman D
Shenk T
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.75.24.12319-12330.2001
Published
2001-12-00
Pages
12319-30
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC116128
Subset
IM
Grants
NCI NIH HHS · P01 CA087661 · United States
NCI NIH HHS · CA87661 · United States
External Links
PubMed source DOI: 10.1128/JVI.75.24.12319-12330.2001 PMC Full Text View journal details
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