Coinfection with Hepatitis C Virus among HIV-1-Infected Individuals Increases Proinflammatory Cytokines and HIV-1 Disease Severity

Abstract

Submit Manuscript | http://medcraveonline.com infection that is spontaneously cleared [3].However, in cases of HIV-1 and HCV coinfection, the number of chronic HCV infections rises to 90% [4]. The result of any viral infection depends on the interplay between the activation of host cellular factors to the infection and the viral mechanisms that counteract them [5]. HCV is responsible for activating antiviral interferon (IFN)-α/β expression, but irrespective of the expression of these cytokines, HCV can still replicate within the liver [6]. This could be due to the fact that the nonstructural proteins, nonstructural protein (NS)3 and NS5A, and the structural protein E2 can block the expression as well as transcription of IFN-α/β genes. Also, the NS5A protein induces expression of interleukin (IL)-8, associated with IFN-α inhibition [7] HCV can also block the antiviral action of natural killer (NK) and NKT cells thus hindering the expression of IFN-γ (an antiviral cytokine) due to the interaction between E2 and NK-cell CD81 molecule [8]. The production of cytokines by dendritic cells (DCs) is particularly affected by chronic HCV infection and there are contradictory reports concerning the expression of Th1 cytokines, with some studies suggesting that a Th1 response is suppressed [9] and some studies suggesting a progressive liver injury during chronic HCV has been associated with an increase in the Th1 responseassociated cytokines [10]. In this regard, HCV CD4 + T cells also play an important role in providing an adaptive response by activating cytotoxic and humoral responses. This can involve the secretion AbstractHIV-1, along with hepatitis B and C viruses (HBV and HCV), are known to share similar routes of transmission, including intravenous drug use, blood transfusions, sexual intercourse, and perinatal exposure. Thus, coinfection with HIV-1 and HBV or HCV is common. HIV-1 impacts the natural course of HBV and HCV infection by accelerating the progression of HBV/HCV-associated liver disease toward endstage cirrhosis and quantitative depletion of the CD4+ T-cell compartment. HBV or HCV coinfection with HIV-1 has also been associated with increased mortality when compared to either infection alone. In particular, we focus on the impact of coinfection with HCV on the HIV-1 pathogenic process in patients in the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort. Comparing HIV-1 mono-infection with HIV-1/HCV coinfection allows defining the detrimental effect of HCV coinfection as it relates to viral pathogenesis, disease progression, and the associated immune response during the course of this complex interplay, in the background of drug abuse, which is an important risk factor to both HIV-1 and HCV infection and on HIV-1 disease severity. The uniqueness of this study includes the fact that the patients are part of a cohort of HIV-1-infected individuals whose drug histories have been recorded longitudinally.