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GB virus C infection is associated with a reduced rate of reactivation of latent HIV and protection against activation-induced T-cell death
Journal article   Open access   Peer reviewed

GB virus C infection is associated with a reduced rate of reactivation of latent HIV and protection against activation-induced T-cell death

Robert T RYDZE, Nirjal BHATTARAI and Jack T STAPLETON
Antiviral therapy, Vol.17(7), pp.1271-1279
2012
DOI: 10.3851/IMP2309
PMCID: PMC3709856
PMID: 22951385
url
https://doi.org/10.3851/IMP2309View
Published (Version of record) Open Access

Abstract

Background: GB virus C (GBV-C) coinfection is associated with reduced immune activation and a block in CD4(+) T-cell proliferation following interleukin-2 (IL-2) therapy in HIV-infected individuals. We examined peripheral blood mononuclear cells (PBMCs) from HIV-infected subjects with and without GBV-C viraemia to determine if GBV-C correlated with reactivation of latent HIV, T-cell proliferation or T-cell survival following in vitro activation with phytohaemagglutinin A and IL-2 (PHA/IL-2). Methods: HIV-infected subjects whose HIV viral load was suppressed on combination antiretroviral therapy (cART) for >6 months were studied. PBMCs were cultured with and without PHA/IL-2 and monitored for HIV reactivation, proliferation and survival. GBV-C viraemia and in vitro replication were detected by real-time RT-PCR. HIV reactivation was determined by measuring HIV p24 antigen in culture supernatants. Proliferation was measured by counting viable cells and survival measured by flow cytometry. Results: Of 49 HIV-infected individuals, 26 had GBV-C viraemia. Significantly less HIV reactivation and PBMC proliferation following in vitro activation with PHA/IL-2 was observed in samples from GBV-C viraemic subjects compared with non-viraemic controls. Following 5 weeks in culture, GBV-C replication was associated with preservation of CD4(+) and CD8(+) T-cells compared with non-viraemic controls. Conclusions: GBV-C appears to inhibit immune activation and IL-2 signalling pathways, which might contribute to a reduction in reactivation of latent HIV from cellular reservoirs. In addition, GBV-C viraemia was associated with a reduction in activation-induced T-cell death. GBV-C-associated T-cell effects could contribute to the observed protective effect of GBV-C coinfection in HIV-infected individuals.
Immunopathology Infectious Diseases Antiviral agents Viral diseases Biological and medical sciences Medical sciences Immunodeficiencies Viral hepatitis Pharmacology. Drug treatments Viral diseases of the lymphoid tissue and the blood. Aids Human viral diseases Immunodeficiencies. Immunoglobulinopathies Antibiotics. Antiinfectious agents. Antiparasitic agents

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