Altered Cellular mRNA Levels in Human Cytomegalovirus-Infected Fibroblasts: Viral Block to the Accumulation of Antiviral mRNAs

Journal of Virology - Tập 75 Số 24 - Trang 12319-12330 - 2001
Edward P. Browne1, Bret A. Wing1, David C. Coleman1, Thomas Shenk1
1Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014

Tóm tắt

ABSTRACTThe 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.

Từ khóa


Tài liệu tham khảo

10.1136/ard.59.suppl_1.i6

10.1038/75556

10.1128/MCB.19.5.3607

10.1089/107999001459123

10.1006/viro.1996.0516

10.1126/science.288.5475.2373

10.1126/science.291.5502.303

10.1089/08892220050193164

10.1128/jvi.71.2.1629-1634.1997

10.1073/pnas.95.25.14863

10.1016/S0966-842X(00)01699-1

Garnett H. M. Increased ability of human embryonic fibroblasts to accumulate Ca2+ due to cytomegalovirus infection.Cytobios 31 1981 107 116

10.1006/viro.1999.0044

10.1128/JVI.75.9.4321-4331.2001

10.1073/pnas.96.22.12536

10.1128/jvi.16.6.1560-1565.1975

10.1128/jvi.49.2.363-370.1984

10.1128/jvi.69.11.6697-6704.1995

10.1073/pnas.96.23.13118

10.1073/pnas.90.3.1107

10.1128/mcb.14.4.2331-2342.1994

10.1006/smim.2001.0294

10.1128/jvi.70.12.8850-8857.1996

10.4049/jimmunol.166.11.6829

Mocarski E. S. Courcelle C. T. Cytomegaloviruses and their replication.Fields virology 4th ed. Knipe D. M. Howley P. M. Griffin D. E. Lamb R. A. Martin M. A. Roizman B. Strauss S. E. 2001 Lippincott-Raven Philadelphia Pa

10.1159/000053964

Miller D. M. Zhang Y. Rahill B. M. Waldman W. J. Sedmak D. D. Human cytomegalovirus inhibits IFN-α-stimulated antiviral and immunoregulatory responses by blocking multiple levels of IFN-α signal transduction.J. Immunol. 162 1999 6107 6113

10.1128/JVI.75.2.750-758.2001

10.1101/gad.864201

10.1006/viro.2000.0551

10.1128/JVI.72.11.9173-9180.1998

10.1016/0092-8674(89)90755-1

10.1016/0092-8674(86)90807-X

10.1073/pnas.121177598

Smyth M. J. J. M. Kelly V. R. Sutton J. E. Davis K. A. Browne T. J. Sayers and J. A. Trapani. Unlocking the secrets of cytotoxic granule proteins. J. Leukoc. Biol. 70: 18–29.

10.1002/jlb.57.5.795

10.1007/BF01311001

10.1016/S0165-2478(97)00073-4

10.1016/S0888-7543(05)80307-6

10.1128/jvi.71.6.4638-4648.1997

10.1128/jvi.69.12.7960-7970.1995

10.1073/pnas.94.25.13985

10.1073/pnas.95.24.14470

Thông tin
Thông tin xuất bản

Journal of Virology

Tập 75 Số 24

12319-12330

Thông tin tác giả