title: GB virus C infection is associated with a reduced rate of reactivation of latent HIV and protection against activation-induced T-cell death.
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.
authors.affiliation: The Iowa City Veterans Affairs Medical Center, Iowa City, IA, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Rydze
authors.forename: Nirjal
authors.initials: N
authors.lastname: Bhattarai
authors.forename: Jack T
authors.initials: JT
authors.lastname: Stapleton
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D016022:Case-Control Studies; D016923:Cell Death; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D060085:Coinfection / Q000821:virology; D018178:Flaviviridae Infections / Q000276:immunology / Q000821:virology; D005434:Flow Cytometry; D029407:GB virus C / Q000472:pathogenicity* / Q000502:physiology; D016655:HIV Core Protein p24 / Q000032:analysis / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity; D006525:Hepatitis, Viral, Human / Q000276:immunology / Q000821:virology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins / Q000276:immunology / Q000494:pharmacology; D015398:Signal Transduction; D019562:Viral Load; D014766:Viremia / Q000821:virology; D014775:Virus Activation; D017735:Virus Latency
chemical_list: D016655:HIV Core Protein p24; D007376:Interleukin-2; D010835:Phytohemagglutinins