Viruses within the Flaviviridae decrease CD4 expression and inhibit HIV replication in human CD4+ cells

Jinhua Xiang; James H McLinden; Robert A Rydze; Qing Chang; Thomas M Kaufman; Donna Klinzman; Jack T Stapleton

doi:10.4049/jimmunol.0902276

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Viruses within the Flaviviridae decrease CD4 expression and inhibit HIV replication in human CD4+ cells

Journal article

Peer reviewed

Viruses within the Flaviviridae decrease CD4 expression and inhibit HIV replication in human CD4+ cells

Jinhua Xiang, James H McLinden, Robert A Rydze, Qing Chang, Thomas M Kaufman, Donna Klinzman and Jack T Stapleton

The Journal of immunology (1950), Vol.183(12), pp.7860-7869

12/15/2009

DOI: 10.4049/jimmunol.0902276

PMCID: PMC3557943

PMID: 19923460

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Abstract

Viral infections alter host cell homeostasis and this may lead to immune evasion and/or interfere with the replication of other microbes in coinfected hosts. Two flaviviruses are associated with a reduction in HIV replication or improved survival in HIV-infected people (dengue virus (DV) and GB virus type C (GBV-C)). GBV-C infection and expression of the GBV-C nonstructural protein 5A (NS5A) and the DV NS5 protein in CD4(+) T cells inhibit HIV replication in vitro. To determine whether the inhibitory effect on HIV replication is conserved among other flaviviruses and to characterize mechanism(s) of HIV inhibition, the NS5 proteins of GBV-C, DV, hepatitis C virus, West Nile virus, and yellow fever virus (YFV; vaccine strain 17D) were expressed in CD4(+) T cells. All NS5 proteins inhibited HIV replication. This correlated with decreased steady-state CD4 mRNA levels and reduced cell surface CD4 protein expression. Infection of CD4(+) T cells and macrophages with YFV (17D vaccine strain) also inhibited HIV replication and decreased CD4 gene expression. In contrast, mumps virus was not inhibited by the expression of flavivirus NS5 protein or by YFV infection, and mumps infection did not alter CD4 mRNA or protein levels. In summary, CD4 gene expression is decreased by all human flavivirus NS5 proteins studied. CD4 regulation by flaviviruses may interfere with innate and adaptive immunity and contribute to in vitro HIV replication inhibition. Characterization of the mechanisms by which flaviviruses regulate CD4 expression may lead to novel therapeutic strategies for HIV and immunological diseases.

Phosphoproteins - biosynthesis

Hepatitis, Viral, Human - immunology

GB virus C - immunology

Jurkat Cells

HIV Infections - virology

Humans

Homeostasis - immunology

Virus Replication - immunology

Viral Nonstructural Proteins - biosynthesis

Flaviviridae Infections - virology

Viral Nonstructural Proteins - physiology

CD4-Positive T-Lymphocytes - immunology

HIV Infections - immunology

HIV-1 - immunology

HIV-1 - growth & development

Down-Regulation - immunology

Hepatitis, Viral, Human - virology

Phosphoproteins - physiology

CD4 Antigens - biosynthesis

CD4-Positive T-Lymphocytes - virology

CD4 Antigens - metabolism

Flaviviridae Infections - immunology

Details

Title: Subtitle: Viruses within the Flaviviridae decrease CD4 expression and inhibit HIV replication in human CD4+ cells
Creators: Jinhua Xiang - Department of Internal Medicine, Iowa City Veterans Affairs Medical Center and University of Iowa, Iowa City, IA 52242, USA
James H McLinden
Robert A Rydze
Qing Chang
Thomas M Kaufman
Donna Klinzman
Jack T Stapleton
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.183(12), pp.7860-7869
DOI: 10.4049/jimmunol.0902276
PMID: 19923460
PMCID: PMC3557943
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: R01 AI058740 / NIAID NIH HHS UL1 RR024979 / NCRR NIH HHS R01AI-58740 / NIAID NIH HHS
Language: English
Date published: 12/15/2009
Academic Unit: Microbiology and Immunology; Infectious Diseases; Internal Medicine
Record Identifier: 9984094348402771

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