GB virus C coinfection in advanced HIV type-1 disease is associated with low CCR5 and CXCR4 surface expression on CD4+ T-cells

Carolynne Schwarze-Zander, Markus Neibecker, Sabrina Othman, Cristina Tural, Bonaventura Clotet, Jason T. Blackard, Bernd Kupfer, Guido Luechters, Ray T. Chung, Jürgen K. Rockstroh, Ulrich Spengler

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30 Citations (Scopus)

Abstract

Background: Coinfection with the flavivirus GB virus C (GBV-C) is frequent in patients suffering from HIV type-1 (HIV-1) infection because of shared routes of transmission. GBV-C coinfection has been proposed to exert a beneficial influence on HIV-1 infection. In vitro studies demonstrated down-regulation of C-C chemokine receptor type 5 (CCR5) as a potential mechanism by which GBV-C modulates HIV-1 disease progression. We therefore studied surface expression of the two major HIV-1 coreceptors, CCR5 and CXC chemokine receptor type 4 (CXCR4), on CD4+ and CD8+ T-cells in 128 HIV-1-positive patients stratified with respect to their GBV-C status, immune function and highly active antiretroviral therapy (HAART) status in vivo. Methods: GBV-C infection was studied in 128 HIV-1-infected patients by nested reverse transcriptase PCR. Fluorescence-activated cell sorting analysis was used to measure CCR5 and CXCR4 surface expression on CD4+ and CD8+ T-cells. Results: GBV-C RNA replication was detected in 30% (38/128) of patients. In HIV-1-positive patients with advanced immunodeficiency, we found up-regulation of CCR5 surface expression on CD4+ T-cells; however, in patients with GBV-C coinfection, no up-regulation of CCR5 CD4+ T-cells was detected. Furthermore, CXCR4 surface expression was reduced in GBV-C-coinfected patients. These findings were independent of HAART status and HIV-1 viral load. HIV-1 coreceptor expression on CD8+ T-cells was not altered in patients with GBV-C coinfection. Conclusions: GBV-C coinfection in HIV-1 disease leads to reduced expression of the two major HIV-1 coreceptors, CCR5 and CXCR4, on CD4+ T-cells in patients at an advanced stage of immunodeficiency, providing a possible molecular explanation for the clinical benefit of GBV-C coinfection in late-stage HIV-1 disease. ©2010 International Medical Press.
Original languageEnglish
Pages (from-to)745-752
JournalAntiviral Therapy
Volume15
Issue number5
DOIs
Publication statusPublished - 8 Oct 2010

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