HCV and HIV Infection Stimulate Distinct Immune Response Patterns

About one-third of HIV positive people in the U.S. are estimated to be coinfected with hepatitis C virus (HCV), and HIV-HCV coinfection has been linked to more rapid progression of liver fibrosis and poorer response to treatment with pegylated interferon plus ribavirin.

As reported at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) this week in Chicago, researchers from the National Institutes of Health examined the molecular and immunological basis for host immune responses to HIV and HCV.

Using Affymetrix U133A gene chips, they analyzed gene expression profiles in peripheral blood mononuclear cells (PBMCs) from 33 patients:

• 7 HIV negative;

• 7 HCV monoinfected and viremic;

• 8 HIV monoinfected and viremic;

• 5 HIV-HCV coinfected;

• 6 HIV positive and non-viremic.

A SAM algorithm was used to determine the genes that were differentially expressed across the different patient groups. Validation of DNA microarray data was performed using a bDNA multiplex assay, flow cytometry, and ELISA.

Results

• Gene expression profiles in PBMCs showed that HIV viremia upregulates genes associated with immune activation, while HCV viremia upregulates genes associated with immunoregulatory pathways.

• HCV viremia was associated with abnormalities in non-T-cells, suggesting a global effect of HCV on the immune system.

• Ingenuity function analysis revealed distinct pathways of innate immune activation involved in HCV and HIV infection.

• Interferon-induced genes were expressed at a higher level in PBMCs from HIV positive individuals (P<0.01).

• Functional assays confirmed enhanced immunoregulatory activity among HCV infected individuals, resulting in an inability to mount an effective anti-HCV immune response.

Conclusion

"HCV and HIV infection leave distinct genetic imprints of immune activation profiles in PBMCs," the investigators concluded. "Of note, HIV viremia induces an immune activated state whereas HCV infection induces immunoregulatory pathways resulting in immunologic quiescence."

They added that, "Aberrant type-I interferon response seen exclusively in HIV-infected individuals may be responsible for poor therapeutic response seen in HIV-HCV coinfected patients to current standard of care [for hepatitis C]."

National Institutes of Health/National Institute for Allergy and Infectious Diseases, Bethesda, MD.

09/18/07

Reference
MY Yan, KN Reitano, J Yang, and others. Chronic HIV and Hepatitis C Infection Induce Distinct Immunologic Imprints that Relate to Pathogenesis of Liver Fibrosis and Therapeutic Response to Interferons. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, September 17-20, 2007. Abstract V-1384.