Journal article
Inhibition of HIV-1 replication by GB virus C infection through increases in RANTES, MIP-1α, MIP-1β, and SDF-1
The Lancet (British edition), Vol.363(9426), pp.2040-2046
2004
DOI: 10.1016/S0140-6736(04)16453-2
PMID: 15207954
Abstract
Background People coinfected with HIV and GB virus C (GBV-C) have lower mortality than HIV-positive individuals without GBV-C infection. HIV uses either of the chemokine receptors CCR5 and CXCR4 for entry into CD4-positive cells. Longer survival in HIV-positive individuals is associated with high serum concentrations of ligands for CCR5 (RANTES [regulated on activation, normal T-cell expressed and secreted] and macrophage inflammatory proteins [MIP] 1alpha and 1beta) and CXCR4 (stromal-derived factor [SDF-1]), and with decreased expression of CCR5 on lymphocytes. Methods Peripheral-blood mononuclear cells were coinfected with GBV-C and HIV, and HIV replication was monitored by measuring infectivity and HIV p24 antigen production. Chemokine secretion was measured by ELISA, chemokine-receptor expression by flow cytometry, and cellular chemokine mRNA expression by differential hybridisation. Findings GBV-C infection of peripheral-blood mononuclear cells resulted in decreased replication of both clinical and laboratory HIV strains that use either CCR5 or CXCR4 as their coreceptor. Inhibition was related to the dose and timing of the GBV-C infection. Expression of mRNA for RANTES, MIP-1alpha, MIP-1beta, and SDF-1 and secretion of the chemokines into culture supernatants were higher in GBV-C-infected cells than in mock-infected cells. The inhibitory effect of GBV-C on HIV replication was blocked by incubation with neutralising antibodies against the relevant chemokines, and surface expression of CCR5 was significantly lower in GBV-C-infected cells than in mock-infected cells. Interpretation GBV-C induces HIV-inhibitory chemokines and reduces expression of the HIV coreceptor CCR5 in vitro. This study provides insight into the epidemiological association between GBV-C infection and longer survival in HIV-infected individuals.
Details
- Title: Subtitle
- Inhibition of HIV-1 replication by GB virus C infection through increases in RANTES, MIP-1α, MIP-1β, and SDF-1
- Creators
- JINHUA XIANG - Research Service and Department of Internal Medicine, Iowa City, VA Medical Center and University of Iowa, Iowa City, IA, United StatesSarah L GEORGE - Research Service and Department of Internal Medicine, Iowa City, VA Medical Center and University of Iowa, Iowa City, IA, United StatesSabina WÜNSCHMANN - Research Service and Department of Internal Medicine, Iowa City, VA Medical Center and University of Iowa, Iowa City, IA, United StatesQING CHANG - Research Service and Department of Internal Medicine, Iowa City, VA Medical Center and University of Iowa, Iowa City, IA, United StatesDonna KLINZMAN - Research Service and Department of Internal Medicine, Iowa City, VA Medical Center and University of Iowa, Iowa City, IA, United StatesJack T STAPLETON - Research Service and Department of Internal Medicine, Iowa City, VA Medical Center and University of Iowa, Iowa City, IA, United States
- Resource Type
- Journal article
- Publication Details
- The Lancet (British edition), Vol.363(9426), pp.2040-2046
- Publisher
- Lancet
- DOI
- 10.1016/S0140-6736(04)16453-2
- PMID
- 15207954
- ISSN
- 0140-6736
- eISSN
- 1474-547X
- Language
- English
- Date published
- 2004
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Internal Medicine
- Record Identifier
- 9984094525502771
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