Human immunodeficiency virus and hepatitis C infections induce distinct immunologic imprints in peripheral mononuclear cells.
Coinfection with hepatitis C virus (HCV) is present in one-third of all human immunodeficiency virus (HIV)-infected individuals in the United States and is associated with rapid progression of liver fibrosis and poor response to pegylated interferon (IFN) and ribavirin. In this study we examined gene expression profiles in peripheral blood mononuclear cells (PBMCs) from different groups of individuals who are monoinfected or coinfected with HIV and HCV. Data showed that HIV and HCV viremia up-regulate genes associated with immune activation and immunoregulatory pathways. HCV viremia is also associated with abnormalities in all peripheral immune cells, suggesting a global effect of HCV on the immune system. Interferon-alpha-induced genes were expressed at a higher level in PBMCs from HIV-infected individuals. HCV and HIV infections leave distinct profiles or gene expression of immune activation in PBMCs. HIV viremia induces an immune activated state; by comparison, HCV infection induces immunoregulatory and proinflammatory pathways that may contribute to progression of liver fibrosis.


CONCLUSIONS
An aberrant type-I IFN response seen exclusively in HIV-infected individuals could be responsible for the poor therapeutic response experienced by HIV/HCV coinfected individuals receiving interferon-alpha-based current standard of care.
Kottilil
Shyam
S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. skottilil@niaid.nih.gov
Yan
Michael Y
MY
Reitano
Kristin N
KN
Zhang
Xiaozhen
X
Lempicki
Richard
R
Roby
Gregg
G
Daucher
Marybeth
M
Yang
Jun
J
Cortez
Karoll J
KJ
Ghany
Marc
M
Polis
Michael A
MA
Fauci
Anthony S
AS
D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D005260:Female; D015870:Gene Expression / Q000276:immunology*; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006526:Hepatitis C / Q000150:complications / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D055815:Young Adult