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PMID: 9399963 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Interferon-gamma and tumor necrosis factor-alpha specifically induce formation of cytomegalovirus-permissive monocyte-derived macrophages that are refractory to the antiviral activity of these cytokines.

The Journal of clinical investigation ·Vol. 100 ·No. 12 ·1997-12-15 ·Pages 3154-63

Söderberg-Nauclér C, Fish KN, Nelson JA

Abstract

Monocytes/macrophages are key cells in the pathogenesis of human cytomegalovirus (HCMV). Although HCMV infection in monocytes is restricted to early events of gene expression, productive infection has been demonstrated in differentiated macrophages in vitro. We examined the cellular and cytokine components that are essential for HCMV replication in Concanavalin A-stimulated monocyte-derived macrophages (MDM). By negative selection, depletion of CD8+ T lymphocytes, but not CD4+ T lymphocytes, CD19+ B cells, or CD56+ NK cells, resulted in a 60-70% reduction in the number of HCMV-infected MDM, and a 4 log decrease in virus production. Neutralization of IFN-gamma and TNF-alpha, but not IL-1, IL-2, or TGF-beta, decreased production of virus by 4 logs and 2 logs, respectively. Subsequently, addition of recombinant IFN-gamma or TNF-alpha to purified monocyte cultures was sufficient to produce HCMV-permissive MDM. While IFN-gamma and TNF-alpha possess antiviral properties, addition of these cytokines to permissive MDM cultures did not affect production of HCMV. Thus, rather than inhibiting replication of HCMV, IFN-gamma and TNF-alpha specifically induce differentiation of monocytes into HCMV-permissive MDM, which are resistant to the antiviral effects of these cytokines.

MeSH Terms
Antiviral Agents/pharmacology CD8-Positive T-Lymphocytes/immunology Cell Communication Cell Differentiation Concanavalin A/pharmacology Cytomegalovirus/drug effects,physiology Histocompatibility Antigens Class I/immunology Humans Interferon-gamma/immunology,pharmacology Macrophages/cytology,drug effects,virology Mitogens/pharmacology Monocytes/cytology Tumor Necrosis Factor-alpha/immunology,pharmacology Virus Replication/drug effects
Chemicals
Antiviral Agents Histocompatibility Antigens Class I Mitogens Tumor Necrosis Factor-alpha Concanavalin A Interferon-gamma
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Söderberg-Nauclér C
Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, Oregon 97201-3098, USA.
Fish K N
Nelson J A
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI119871
Published
1997-12-15
Pages
3154-63
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508529
Subset
IM
Grants
NIAID NIH HHS · R01 AI 21640 · United States
External Links
PubMed source DOI: 10.1172/JCI119871 PMC Full Text View journal details
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