Abstract
BackgroundCo-infection with human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) is associated with faster progression of liver disease and an increase in HCV persistence. However, the mechanism by which HIV-1 accelerates the progression of HCV liver disease remains unknown.ResultsHIV-1/HCV co-infection is associated with increased expression of interferon gamma-induced protein-10 (IP-10) mRNA in peripheral blood mononuclear cells (PBMCs). HCV RNA levels were higher in PBMCs of patients with HIV-1/HCV co-infection than in patients with HCV mono-infection. HIV-1 Tat and IP-10 activated HCV replication in a time-dependent manner, and HIV-1 Tat induced IP-10 production. In addition, the effect of HIV-1 Tat on HCV replication was blocked by anti-IP-10 monoclonal antibody, demonstrating that the effect of HIV-1 Tat on HCV replication depends on IP-10. Taken together, these results suggest that HIV-1 Tat protein activates HCV replication by upregulating IP-10 production.ConclusionsHIV-1/HCV co-infection is associated with increased expression of IP-10 mRNA and replication of HCV RNA. Furthermore, both HIV-1 Tat and IP-10 activate HCV replication. HIV-1 Tat activates HCV replication by upregulating IP-10 production. These results expand our understanding of HIV-1 in HCV replication and the mechanism involved in the regulation of HCV replication mediated by HIV-1 during co-infection.
Highlights
Co-infection with human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) is associated with faster progression of liver disease and an increase in HCV persistence
induced protein-10 (IP-10) mRNA and HCV RNA levels are increased in patients with HIV-1/HCV co-infection compared to HCV monoinfection We evaluated the IP-10 mRNA levels in Peripheral blood mononuclear cell (PBMC) isolated from healthy individuals and HCV mono-infected and HIV-1/HCV co-infected patients
Can replicate in PBMCs [8,9], so we compared the levels of HCV RNA in PBMCs of HCV mono-infected and HIV-1/HCV co-infected patients
Summary
Co-infection with human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) is associated with faster progression of liver disease and an increase in HCV persistence. Hepatitis C virus (HCV) is a major etiological agent of chronic liver disease. Due to similar routes of transmission, co-infection with HCV and human immunodeficiency virus-1 (HIV-1) is common, with the prevalence of co-infection ranging from 4 to 5 million patients [1]. HCV-related liver diseases have become a major source of morbidity and mortality in HIV-1infected patients [2]. Once chronic infection is established, patients with HIV-1/HCV co-infection have a higher rate of viral persistence, faster progression, and earlier development of end-stage liver disease, compared to HCV mono-infected patients [3,4]. Infection with HIV-1 is associated with higher HCV viral levels in sera
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