GB virus C coinfection in advanced HIV type-1 disease is associated with low CCR5 and CXCR4 surface expression on CD4(+) T-cells.
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.
Schwarze-Zander
Carolynne
C
Department of Internal Medicine I, University Hospital Bonn, Germany. carolynne.schwarze-zander@ukb.uni-bonn.de
Neibecker
Markus
M
Othman
Sabrina
S
Tural
Cristina
C
Clotet
Bonaventura
B
Blackard
Jason T
JT
Kupfer
Bernd
B
Luechters
Guido
G
Chung
Ray T
RT
Rockstroh
Jürgen K
JK
Spengler
Ulrich
U
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D018178:Flaviviridae Infections / Q000150:complications* / Q000821:virology; D005434:Flow Cytometry; D029407:GB virus C / Q000502:physiology*; D015658:HIV Infections / Q000150:complications* / Q000503:physiopathology / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006525:Hepatitis, Viral, Human / Q000150:complications* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*
D019713:Receptors, CCR5; D019718:Receptors, CXCR4