Hepatitis C virus (HCV) infects more than 170 million people worldwide and is the main cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Although the newly developed direct-acting antivirals (DAAs) have transformed the treatment of HCV infection, controlling HCV infection on a global scale remains a challenge because of the high cost, low resistance barrier of DAAs and lack of HCV vaccine. The host immune responses associated with HCV infection, especially HCV-specific T cellular immunity, determine the outcome of HCV infection: either acute or chronic infection. It is important to fully interpret the immunopathogenesis of HCV infection and consequently to exploit effective strategies to eliminate HCV. Here, we review the current progress in HCV immunology, which will deepen our understanding of the spectrum of HCV infection and immunity in humans.
Background: The CD39/CD73/adenosine suppression pathway correlates with disease progression in patients with chronic human immunodeficiency virus 1 (HIV-1) infection; however, the relationships between this pathway in B cells and innate immune hyperactivation remain largely undefined. Methods: In this study, we examined CD39 and CD73 expression, and adenosine production by B cells from 136 patients with chronic HIV-1 infection. Results: The CD39 and CD73 expression levels on total B cells (and their subsets) decreased continuously in typical progressors (TPs), but were gradually recovered in complete responders. In TPs, the frequencies of CD39 + , CD73 + , and CD39 + CD73 + B cells inversely correlated with HIV-1 viral load and positively correlated with CD4 T cell counts, but also positively associated with CD4/CD8 ratioes and inversely correlated with markers for intestinal epithelial injury and microbial translocation. Furthermore, B cells from TPs showed a markedly reduced capacity to generate CD39/CD73-dependent extracellular adenosine; the loss of this capacity was more serious in patients with acquired immunodeficiency syndrome. In vitro, increased adenosine could inhibit the activation of monocytes and suppress the ability of monocytes and T cells to produce TNF-alpha, regardless of their infection status. Moreover, adenosine could inhibit activation-induced HIV-1 virion production and p24 expression. Conclusions: These findings provided a new role of B cell pathology in HIV-1 infection, in which the skewed CD39/ CD73/adenosine pathway in B cells linked to microbial translocation-induced innate immune hyperactivation, supporting the notion that regulating the adenosine pathway in B cells might be an attractive approach to treat patients with HIV-1-infection.
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