title: 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.
authors: 1 Department of Pathology and Laboratory Medicine, University of Louisville School of Medicine , Louisville, Kentucky.
authors: Rafael
authors: R
authors: Fernandez-Botran
authors: Swati
authors: S
authors: Joshi-Barve
authors: Smita
authors: S
authors: Ghare
authors: Shirish
authors: S
authors: Barve
authors: Mary
authors: M
authors: Young
authors: Michael
authors: M
authors: Plankey
authors: Jose
authors: J
authors: Bordon
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000328:Adult; D020170:Caspase 1 / Q000097:blood; D015331:Cohort Studies; D060085:Coinfection / Q000150:complications / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000150:complications / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000821:virology; D008875:Middle Aged; D011446:Prospective Studies; D043222:Ubiquitin Thiolesterase; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D016207:Cytokines; D014452:Ubiquitins; C074034:ISG15 protein, human; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase; D010450:Endopeptidases; C485560:USP18 protein, human; D043222:Ubiquitin Thiolesterase; D020170:Caspase 1