The Journal of Experimental Medicine
ELISpot, FluoroSpot and ELISA kits from Mabtech
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

Published online 19 February 2001.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 349K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Presti, R. M.
Right arrow Articles by Virgin, H. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Presti, R. M.
Right arrow Articles by Virgin, H. W., IV
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/2001/2/483/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 4, February 19, 2001 483-496


Original Article

Novel Cell Type–Specific Antiviral Mechanism of Interferon {gamma} Action in Macrophages

Rachel M. Prestia, Daniel L. Popkina, Megan Connicka, Susanne Paetzolda, and Herbert W. Virgin, IVa

a Department of Pathology and Immunology and the Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110
Dept. of Pathology and Immunology and Dept. of Molecular Microbiology, Washington University School of Medicine, Box 8118, 660 South Euclid Ave., St. Louis, MO 63110.314-362-4096314-362-9223

virgin{at}immunology.wustl.edu

Interferon (IFN)-{gamma} and macrophages (M{phi}) play key roles in acute, persistent, and latent murine cytomegalovirus (MCMV) infection. IFN-{gamma} mechanisms were compared in embryonic fibroblasts (MEFs) and bone marrow M{phi} (BMM{phi}). IFN-{gamma} inhibited MCMV replication in a signal transducer and activator of transcription (STAT)-1{alpha}–dependent manner much more effectively in BMM{phi} (~100-fold) than MEF (5–10-fold). Although initial STAT-1{alpha} activation by IFN-{gamma} was equivalent in MEF and BMM{phi}, microarray analysis demonstrated that IFN-{gamma} regulates different sets of genes in BMM{phi} compared with MEFs. IFN-{gamma} inhibition of MCMV growth was independent of known mechanisms involving IFN-{alpha}/β, tumor necrosis factor {alpha}, inducible nitric oxide synthase, protein kinase RNA activated (PKR), RNaseL, and Mx1, and did not involve IFN-{gamma}–induced soluble mediators. To characterize this novel mechanism, we identified the viral targets of IFN-{gamma} action, which differed in MEF and BMM{phi}. In BMM{phi}, IFN-{gamma} reduced immediate early 1 (IE1) mRNA during the first 3 h of infection, and significantly reduced IE1 protein expression for 96 h. Effects of IFN-{gamma} on IE1 protein expression were independent of RNaseL and PKR. In contrast, IFN-{gamma} had no significant effects on IE1 protein or mRNA expression in MEFs, but did decrease late gene mRNA expression. These studies in primary cells define a novel mechanism of IFN-{gamma} action restricted to M{phi}, a cell type key for MCMV pathogenesis and latency.

Key Words: interferon {gamma} • cytomegalovirus • signal transducer and activator of transcription 1 • microarray analysis • macrophage


Abbreviations used in this paper: BM, bone marrow; EMSA, electrophoretic mobility shift assay; HBV, hepatitis B virus; HCMV, human CMV; IE, immediate early; iNOS, inducible nitric oxide synthase; MCMV, murine CMV; MEF, murine embryonic fibroblast; M{phi}, macrophage; MOI, multiplicity of infection; PKR, protein kinase RNA activated; STAT, signal transducer and activator of transcription.

© 2001 The Rockefeller University Press


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS