Characterization of a peptide domain within the GB virus C NS5A phosphoprotein that inhibits HIV replication

Jinhua Xiang; James H McLinden; Qing Chang; Emma L Jordan; Jack T Stapleton

doi:10.1371/journal.pone.0002580

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Characterization of a peptide domain within the GB virus C NS5A phosphoprotein that inhibits HIV replication

Journal article

Open access

Peer reviewed

Characterization of a peptide domain within the GB virus C NS5A phosphoprotein that inhibits HIV replication

Jinhua Xiang, James H McLinden, Qing Chang, Emma L Jordan and Jack T Stapleton

PloS one, Vol.3(7), pp.e2580-e2580

07/02/2008

DOI: 10.1371/journal.pone.0002580

PMCID: PMC2440355

PMID: 18596910

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Abstract

GBV-C infection is associated with prolonged survival in HIV-infected people and GBV-C inhibits HIV replication in co-infection models. Expression of the GBV-C nonstructural phosphoprotein 5A (NS5A) decreases surface levels of the HIV co-receptor CXCR4, induces the release of SDF-1 and inhibits HIV replication in Jurkat CD4+ T cell lines. Jurkat cell lines stably expressing NS5A protein and peptides were generated and HIV replication in these cell lines assessed. HIV replication was significantly inhibited in all cell lines expressing NS5A amino acids 152-165. Substitution of an either alanine or glycine for the serine at position 158 (S158A or S158G) resulted in a significant decrease in the HIV inhibitory effect. In contrast, substituting a phosphomimetic amino acid (glutamic acid; S158E) inhibited HIV as well as the parent peptide. HIV inhibition was associated with lower levels of surface expression of the HIV co-receptor CXCR4 and increased release of the CXCR4 ligand, SDF-1 compared to control cells. Incubation of CD4+ T cell lines with synthetic peptides containing amino acids 152-167 or the S158E mutant peptide prior to HIV infection resulted in HIV replication inhibition compared to control peptides. Expression of GBV-C NS5A amino acids 152-165 are sufficient to inhibit HIV replication in vitro, and the serine at position 158 appears important for this effect through either phosphorylation or structural changes in this peptide. The addition of synthetic peptides containing 152-167 or the S158E substitution to Jurkat cells resulted in HIV replication inhibition in vitro. These data suggest that GBV-C peptides or a peptide mimetic may offer a novel, cellular-based approach to antiretroviral therapy.

Anti-HIV Agents - pharmacology

Virus Replication - drug effects

Phosphorylation

Phosphoproteins - pharmacology

HIV - physiology

Peptides - chemistry

Jurkat Cells

Down-Regulation

Humans

GB virus C

Phosphoproteins - metabolism

HIV - drug effects

Phosphoproteins - chemistry

Viral Nonstructural Proteins - pharmacology

Peptides - pharmacology

Anti-HIV Agents - chemistry

Viral Nonstructural Proteins - chemistry

Peptides - metabolism

Viral Nonstructural Proteins - metabolism

Anti-HIV Agents - metabolism

Details

Title: Subtitle: Characterization of a peptide domain within the GB virus C NS5A phosphoprotein that inhibits HIV replication
Creators: Jinhua Xiang - Iowa City VA Medical Center and the University of Iowa, Iowa City, Iowa, United States of America
James H McLinden
Qing Chang
Emma L Jordan
Jack T Stapleton
Resource Type: Journal article
Publication Details: PloS one, Vol.3(7), pp.e2580-e2580
DOI: 10.1371/journal.pone.0002580
PMID: 18596910
PMCID: PMC2440355
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science
Grant note: R01 AI-58740 / NIAID NIH HHS R01 AI058740 / NIAID NIH HHS T32 GM007337 / NIGMS NIH HHS
Language: English
Date published: 07/02/2008
Academic Unit: Microbiology and Immunology; Infectious Diseases; Internal Medicine
Record Identifier: 9984094576402771

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