Systemic Cytokine and Interferon Responsiveness Patterns in HIV and HCV Mono and Co-Infections

Abstract

The role of host response-related factors in the fast progression of liver disease in individuals co-infected with HIV and HCV viruses remains poorly understood. This study compared patterns of cytokines, caspase-1 activation, endotoxin exposure in plasma as well as interferon signaling in peripheral blood mononuclear cells from HIV/HCV co-infected (HIV⁺/HCV⁺), HCV mono-infected (HIV⁻/HCV⁺), HIV mono-infected (HIV⁺/HCV⁻) female patients and HIV- and HCV-uninfected women (HIV⁻/HCV⁻) who had enrolled in the Women's Interagency HIV Study (WIHS). HIV⁺/HCV⁺ women had higher plasma levels of pro-inflammatory cytokines as well as caspase-1 compared with other groups. Both HIV⁺/HCV⁺ and HIV⁺/HCV⁻ women had significantly higher sCD14 levels compared with other groups. Peripheral blood mononuclear cells from HCV mono-infected patients had reduced levels of phosphorylation of STAT1 compared with other groups as well as lower basal levels of expression of the IFN-stimulated genes, OAS1, ISG15, and USP18 (UBP43). Basal expression of USP18, a functional antagonist of ISG15, as well as USP18/ISG15 ratios were increased in the HIV⁺/HCV⁺ group compared with HIV⁻/HCV⁺ and HIV⁺/HCV⁻ groups. A more pronounced systemic inflammatory profile as well as increased expression ratios of USP18 to ISG15 may contribute to the more rapid progression of liver disease in HIV⁺/HCV⁺ individuals.