Novel Cell Type–Specific Antiviral Mechanism of Interferon γ Action in Macrophages

Interferon (IFN)-γ and macrophages (Mϕ) play key roles in acute, persistent, and latent murine cytomegalovirus (MCMV) infection. IFN-γ mechanisms were compared in embryonic fibroblasts (MEFs) and bone marrow Mϕ (BMMϕ). IFN-γ inhibited MCMV replication in a signal transducer and activator of transcri...

Full description

Bibliographic Details
Main Authors:	Presti, Rachel M., Popkin, Daniel L., Connick, Megan, Paetzold, Susanne, Virgin, Herbert W.
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2001
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195910/

id	pubmed-2195910
recordtype	oai_dc
spelling	pubmed-21959102008-04-14 Novel Cell Type–Specific Antiviral Mechanism of Interferon γ Action in Macrophages Presti, Rachel M. Popkin, Daniel L. Connick, Megan Paetzold, Susanne Virgin, Herbert W. Original Article Interferon (IFN)-γ and macrophages (Mϕ) play key roles in acute, persistent, and latent murine cytomegalovirus (MCMV) infection. IFN-γ mechanisms were compared in embryonic fibroblasts (MEFs) and bone marrow Mϕ (BMMϕ). IFN-γ inhibited MCMV replication in a signal transducer and activator of transcription (STAT)-1α–dependent manner much more effectively in BMMϕ (∼100-fold) than MEF (5–10-fold). Although initial STAT-1α activation by IFN-γ was equivalent in MEF and BMMϕ, microarray analysis demonstrated that IFN-γ regulates different sets of genes in BMMϕ compared with MEFs. IFN-γ inhibition of MCMV growth was independent of known mechanisms involving IFN-α/β, tumor necrosis factor α, inducible nitric oxide synthase, protein kinase RNA activated (PKR), RNaseL, and Mx1, and did not involve IFN-γ–induced soluble mediators. To characterize this novel mechanism, we identified the viral targets of IFN-γ action, which differed in MEF and BMMϕ. In BMMϕ, IFN-γ 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-γ on IE1 protein expression were independent of RNaseL and PKR. In contrast, IFN-γ 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-γ action restricted to Mϕ, a cell type key for MCMV pathogenesis and latency. The Rockefeller University Press 2001-02-19 /pmc/articles/PMC2195910/ /pubmed/11181700 Text en © 2001 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Presti, Rachel M. Popkin, Daniel L. Connick, Megan Paetzold, Susanne Virgin, Herbert W.
spellingShingle	Presti, Rachel M. Popkin, Daniel L. Connick, Megan Paetzold, Susanne Virgin, Herbert W. Novel Cell Type–Specific Antiviral Mechanism of Interferon γ Action in Macrophages
author_facet	Presti, Rachel M. Popkin, Daniel L. Connick, Megan Paetzold, Susanne Virgin, Herbert W.
author_sort	Presti, Rachel M.
title	Novel Cell Type–Specific Antiviral Mechanism of Interferon γ Action in Macrophages
title_short	Novel Cell Type–Specific Antiviral Mechanism of Interferon γ Action in Macrophages
title_full	Novel Cell Type–Specific Antiviral Mechanism of Interferon γ Action in Macrophages
title_fullStr	Novel Cell Type–Specific Antiviral Mechanism of Interferon γ Action in Macrophages
title_full_unstemmed	Novel Cell Type–Specific Antiviral Mechanism of Interferon γ Action in Macrophages
title_sort	novel cell type–specific antiviral mechanism of interferon γ action in macrophages
description	Interferon (IFN)-γ and macrophages (Mϕ) play key roles in acute, persistent, and latent murine cytomegalovirus (MCMV) infection. IFN-γ mechanisms were compared in embryonic fibroblasts (MEFs) and bone marrow Mϕ (BMMϕ). IFN-γ inhibited MCMV replication in a signal transducer and activator of transcription (STAT)-1α–dependent manner much more effectively in BMMϕ (∼100-fold) than MEF (5–10-fold). Although initial STAT-1α activation by IFN-γ was equivalent in MEF and BMMϕ, microarray analysis demonstrated that IFN-γ regulates different sets of genes in BMMϕ compared with MEFs. IFN-γ inhibition of MCMV growth was independent of known mechanisms involving IFN-α/β, tumor necrosis factor α, inducible nitric oxide synthase, protein kinase RNA activated (PKR), RNaseL, and Mx1, and did not involve IFN-γ–induced soluble mediators. To characterize this novel mechanism, we identified the viral targets of IFN-γ action, which differed in MEF and BMMϕ. In BMMϕ, IFN-γ 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-γ on IE1 protein expression were independent of RNaseL and PKR. In contrast, IFN-γ 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-γ action restricted to Mϕ, a cell type key for MCMV pathogenesis and latency.
publisher	The Rockefeller University Press
publishDate	2001
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195910/
_version_	1611432324085317632

Novel Cell Type–Specific Antiviral Mechanism of Interferon γ Action in Macrophages

Similar Items