Fernandez-Botran Rafael, Joshi-Barve Swati, Ghare Smita, Barve Shirish, Young Mary, Plankey Michael, Bordon Jose
1 Department of Pathology and Laboratory Medicine, University of Louisville School of Medicine , Louisville, Kentucky.
J Interferon Cytokine Res. 2014 Nov;34(11):885-93. doi: 10.1089/jir.2014.0006. Epub 2014 Jun 23.
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.
宿主反应相关因素在同时感染HIV和HCV病毒的个体肝病快速进展中的作用仍知之甚少。本研究比较了参与女性机构间HIV研究（WIHS）的HIV/HCV合并感染（HIV(+)/HCV(+)）、HCV单一感染（HIV(-)/HCV(+)）、HIV单一感染（HIV(+)/HCV(-)）的女性患者以及未感染HIV和HCV的女性（HIV(-)/HCV(-)）血浆中细胞因子模式、半胱天冬酶-1激活、内毒素暴露以及外周血单核细胞中的干扰素信号。与其他组相比，HIV(+)/HCV(+)女性的促炎细胞因子以及半胱天冬酶-1的血浆水平更高。HIV(+)/HCV(+)和HIV(+)/HCV(-)女性的sCD14水平均显著高于其他组。与其他组相比，HCV单一感染患者外周血单核细胞中STAT1的磷酸化水平降低，以及干扰素刺激基因OAS1、ISG15和USP18（UBP43）的基础表达水平较低。与HIV(-)/HCV(+)和HIV(+)/HCV(-)组相比，HIV(+)/HCV(+)组中ISG15的功能性拮抗剂USP18的基础表达以及USP18/ISG15比值增加。更明显的全身炎症特征以及USP18与ISG15表达比值的增加可能导致HIV(+)/HCV(+)个体肝病进展更快。
