Journal article
An 85-aa segment of the GB virus type C NS5A phosphoprotein inhibits HIV-1 replication in CD4+ Jurkat T cells
Proceedings of the National Academy of Sciences - PNAS, Vol.103(42), pp.15570-15575
10/17/2006
DOI: 10.1073/pnas.0604728103
PMCID: PMC1622863
PMID: 17030806
Abstract
GB virus type C (GBV-C) is an apparently nonpathogenic virus that replicates in T and B lymphocytes and is a common cause of persistent human infection. Among HIV-1-infected individuals, persistent coinfection with GBV-C is associated with prolonged survival, and infection of blood mononuclear cells or CD4
+
T cells with GBV-C and HIV
in vitro
results in significantly reduced HIV-1 replication. To date, the viral protein(s) that lead to HIV inhibition have not been identified. The GBV-C nonstructural phosphoprotein (NS5A) is predicted to have pleotropic effects on cells, including interactions with the IFN-induced dsRNA-activated protein kinase (PKR). We studied GBV-C NS5A to determine whether it is involved in inhibition of HIV replication. GBV-C NS5A protein from an isolate that was cleared by IFN therapy did not inhibit PKR, whereas NS5A from an isolate that was not cleared by IFN-inhibited PKR function in a yeast genetic system. Both of these GBV-C NS5A proteins were expressed in a CD4
+
T cell line (Jurkat), and both induced a potent, dose-dependent inhibition of HIV-1 replication, thus the effect was independent of PKR inhibition. NS5A induced the release of the chemokine SDF-1 and decreased surface expression of the HIV coreceptor CXCR4, potentially explaining the HIV inhibition. Deletion mapping of the NS5A protein found that an 85-aa region between amino acids 152 and 237 inhibits HIV-1 replication. Thus, GBV-C NS5A protein alters the cellular milieu necessary for HIV-1 replication and may provide a previously undescribed therapeutic approach for anti-HIV therapy.
Details
- Title: Subtitle
- An 85-aa segment of the GB virus type C NS5A phosphoprotein inhibits HIV-1 replication in CD4+ Jurkat T cells
- Creators
- Jinhua Xiang - Research Service and Department of Internal Medicine, Iowa City Veterans Affairs Medical Center and the University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242James H McLinden - Research Service and Department of Internal Medicine, Iowa City Veterans Affairs Medical Center and the University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242Qing Chang - Research Service and Department of Internal Medicine, Iowa City Veterans Affairs Medical Center and the University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242Thomas M Kaufman - Research Service and Department of Internal Medicine, Iowa City Veterans Affairs Medical Center and the University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242Jack T Stapleton - Research Service and Department of Internal Medicine, Iowa City Veterans Affairs Medical Center and the University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.103(42), pp.15570-15575
- DOI
- 10.1073/pnas.0604728103
- PMID
- 17030806
- PMCID
- PMC1622863
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Language
- English
- Date published
- 10/17/2006
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Internal Medicine
- Record Identifier
- 9984094745302771
Metrics
23 Record Views