BACKGROUND & AIMS: Human immunodeficiency virus (HIV) coinfection increases hepatitis C virus (HCV)-related progression of hepatic fibrosis, increases HCV persistence, and decreases response rates to interferon-based anti-HCV therapy. It has remained unclear how HIV, a nonhepatotropic virus, accelerates the progression of liver disease by HCV. METHODS: We explored the possibility that circulating HIV and/or its proteins contribute to the pathogenesis of HCV through engagement of extracellular coreceptors on hepatocytes. RESULTS: In this study, we found that inactivated HIV or gp120 increases HCV replication and enhances HCV-regulated transforming growth factor (TGF)-beta1 expression in both a replicon and an infectious model of HCV. This proviral effect of HIV and gp120 on HCV replication is neutralized by antibodies to CCR5 or CXCR4. However, HIV and gp120 did not alter type I interferon-mediated signaling in these HCV models, indicating that HIV regulates HCV replication through an alternative mechanism. Interestingly, we found that human TGF-beta1 also enhanced HCV replication. The effect of HIV on HCV replication was blocked by a neutralizing antibody to TGF-beta1, indicating that its effects on HCV replication are TGF-beta1 dependent. CONCLUSIONS: These results suggest a novel mechanism by which HIV not only enhances HCV replication but also contributes to progression of hepatic fibrosis.
BACKGROUND & AIMS:Humanimmunodeficiency virus (HIV) coinfection increases hepatitis C virus (HCV)-related progression of hepatic fibrosis, increases HCV persistence, and decreases response rates to interferon-based anti-HCV therapy. It has remained unclear how HIV, a nonhepatotropic virus, accelerates the progression of liver disease by HCV. METHODS: We explored the possibility that circulating HIV and/or its proteins contribute to the pathogenesis of HCV through engagement of extracellular coreceptors on hepatocytes. RESULTS: In this study, we found that inactivated HIV or gp120 increases HCV replication and enhances HCV-regulated transforming growth factor (TGF)-beta1 expression in both a replicon and an infectious model of HCV. This proviral effect of HIV and gp120 on HCV replication is neutralized by antibodies to CCR5 or CXCR4. However, HIV and gp120 did not alter type I interferon-mediated signaling in these HCV models, indicating that HIV regulates HCV replication through an alternative mechanism. Interestingly, we found that humanTGF-beta1 also enhanced HCV replication. The effect of HIV on HCV replication was blocked by a neutralizing antibody to TGF-beta1, indicating that its effects on HCV replication are TGF-beta1 dependent. CONCLUSIONS: These results suggest a novel mechanism by which HIV not only enhances HCV replication but also contributes to progression of hepatic fibrosis.
Authors: Wenyu Lin; Wei-Lun Tsai; Run-Xuan Shao; Guoyang Wu; Lee F Peng; Lydia L Barlow; Woo Jin Chung; Leiliang Zhang; Hong Zhao; Jae-Young Jang; Raymond T Chung Journal: Gastroenterology Date: 2010-03-12 Impact factor: 22.682
Authors: David F Tate; Jared Conley; Robert H Paul; Kathryn Coop; Song Zhang; Wenjin Zhou; David H Laidlaw; Lynn E Taylor; Timothy Flanigan; Bradford Navia; Ronald Cohen; Karen Tashima Journal: Brain Imaging Behav Date: 2010-01-19 Impact factor: 3.978
Authors: B Hajarizadeh; B Grady; K Page; A Y Kim; B H McGovern; A L Cox; T M Rice; R Sacks-Davis; J Bruneau; M Morris; J Amin; J Schinkel; T Applegate; L Maher; M Hellard; A R Lloyd; M Prins; R B Geskus; G J Dore; J Grebely Journal: J Viral Hepat Date: 2015-01-08 Impact factor: 3.728