title: GB virus C infection is associated with altered lymphocyte subset distribution and reduced T cell activation and proliferation in HIV-infected individuals.
abstract: GBV-C infection is associated with prolonged survival and with reduced T cell activation in HIV-infected subjects not receiving combination antiretroviral therapy (cART). The relationship between GBV-C and T cell activation in HIV-infected subjects was examined. HIV-infected subjects on cART with non-detectable HIV viral load (VL) or cART naïve subjects were studied. GBV-C VL and HIV VL were determined. Cell surface markers of activation (CD38(+)/HLA-DR(+)), proliferation (Ki-67+), and HIV entry co-receptor expression (CCR5+ and CXCR4+) on total CD4+ and CD8+ T cells, and on naïve, central memory (CM), effector memory (EM), and effector CD4+ and CD8+ subpopulations were measured by flow cytometry. In subjects with suppressed HIV VL, GBV-C was consistently associated with reduced activation in naïve, CM, EM, and effector CD4+ cells. GBV-C was associated with reduced CD4+ and CD8+ T cell surface expression of activation and proliferation markers, independent of HIV VL classification. GBV-C was also associated with higher proportions of naïve CD4+ and CD8+ T cells, and with lower proportions of EM CD4+ and CD8+ T cells. In conclusion, GBV-C infection was associated with reduced activation of CD4+ and CD8+ T cells in both HIV viremic and HIV RNA suppressed patients. Those with GBV-C infection demonstrated an increased proportion of naive T cells and a reduction in T cell activation and proliferation independent of HIV VL classification, including those with suppressed HIV VL on cART. Since HIV pathogenesis is thought to be accelerated by T cell activation, these results may contribute to prolonged survival among HIV infected individuals co-infected with GBV-C. Furthermore, since cART therapy does not reduce T cell activation to levels seen in HIV-uninfected people, GBV-C infection may be beneficial for HIV-related diseases in those effectively treated with anti-HIV therapy.
authors.affiliation: Research and Medical Services, Iowa City VA Medical Center, Iowa City, Iowa, United States of America. jack-stapleton@uiowa.edu
authors.forename: Jack T
authors.initials: JT
authors.lastname: Stapleton
authors.forename: Kathryn
authors.initials: K
authors.lastname: Chaloner
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Martenson
authors.forename: Jingyang
authors.initials: J
authors.lastname: Zhang
authors.forename: Donna
authors.initials: D
authors.lastname: Klinzman
authors.forename: Jinhua
authors.initials: J
authors.lastname: Xiang
authors.forename: Wendy
authors.initials: W
authors.lastname: Sauter
authors.forename: Seema N
authors.initials: SN
authors.lastname: Desai
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D005260:Female; D018178:Flaviviridae Infections / Q000276:immunology*; D005434:Flow Cytometry; D029407:GB virus C / Q000276:immunology / Q000472:pathogenicity*; D015658:HIV Infections / Q000276:immunology*; D006525:Hepatitis, Viral, Human / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies