GB virus type C infection modulates T-cell activation independently of HIV-1 viral load.
BACKGROUND
Many clinical studies have suggested a beneficial effect of GB virus type C (GBV-C) on the course of HIV-1 infection, but the mechanisms involved in such amelioration are not clear. As recent evidence has implicated cellular activation in HIV-1 pathogenesis, we investigated the effect of GBV-C viremia on T-cell activation in early HIV-1 infection.


METHODS
Forty-eight recently infected HIV-1 patients (23 GBV-C viremic) were evaluated for T-cell counts, expanded immunophenotyping GBV-C RNA detection, and HIV-1 viral load. Nonparametric univariate and multivariate analyses were carried out to identify variables associated with cellular activation, including GBV-C status, HIV-1 viral load, T lymphocyte counts, and CD38 and chemokine (C-C motif) receptor 5 (CCR5) surface expression.


RESULTS
We not only confirmed the positive correlation between HIV-1 viral load and the percentage of T cells positive for CD38(+)CD8(+) but also observed that GBV-C viremic patients had a lower percentage of T cells positive for CD38(+)CD4(+), CD38(+)CD8(+), CCR5(+)CD4(+), and CCR5(+)CD8(+) compared with HIV-1-infected patients who were not GBV-C viremic. In regression models, GBV-C RNA(+) status was associated with a reduction in the CD38 on CD4(+) or CD8(+) T cells and CCR5(+) on CD8(+) T cells, independent of the HIV-1 viral load or CD4(+) and CD8(+) T-cell counts. These results were also supported by the lower expression of CD69 and CD25 in GBV-C viremic patients.


CONCLUSIONS
The association between GBV-C replication and lower T-cell activation may be a key mechanism involved in the protection conferred by this virus against HIV-1 disease progression to immunodeficiency in HIV-1-infected patients.
Infectious Diseases Division, Federal University of São Paulo, Brazil.
Maria Teresa
MT
Maidana-Giret
Tânia M
TM
Silva
Mariana M
MM
Sauer
Helena
H
Tomiyama
José Eduardo
JE
Levi
Katia C
KC
Bassichetto
Anna
A
Nishiya
Ricardo S
RS
Diaz
Ester C
EC
Sabino
Ricardo
R
Palacios
Esper Georges
EG
Kallas
D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D018450:Disease Progression; D005260:Female; D018178:Flaviviridae Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D029407:GB virus C / Q000276:immunology*; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006525:Hepatitis, Viral, Human / Q000150:complications / Q000276:immunology* / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral; D019562:Viral Load; D014766:Viremia; D014779:Virus Replication; D055815:Young Adult
D012367:RNA, Viral