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Original article

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

Corresponding author name: Carolynne Schwarze-Zander
Corresponding author e-mail: carolynne.schwarze-zander@ukb.uni-bonn.de

Citation: Antiviral Therapy 2010; 15:745-752
doi: 10.3851/IMP1602

Date accepted: 28 January 2010
Date published online: 14 July 2010


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.


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