Viral Persistence and Chronicity in Hepatitis C Virus Infection: Role of T-Cell Apoptosis, Senescence and Exhaustion

• Main Authors: Muttiah Barathan, Rosmawati Mohamed, Yean K. Yong, Meganathan Kannan, Jamuna Vadivelu, Alireza Saeidi, Marie Larsson, Esaki Muthu Shankar
• Format: Article
• Language: English
• Published: MDPI AG 2018-10-01
• Series: Cells
• Subjects: apoptosis; viral persistence; hepatitis C virus; immunity; chronic infection
• Online Access: http://www.mdpi.com/2073-4409/7/10/165

Hepatitis C virus (HCV) represents a challenging global health threat to ~200 million infected individuals. Clinical data suggest that only ~10–15% of acutely HCV-infected individuals will achieve spontaneous viral clearance despite exuberant virus-specific immune responses, which is largely attributed to difficulties in recognizing the pathognomonic symptoms during the initial stages of exposure to the virus. Given the paucity of a suitable small animal model, it is also equally challenging to study the early phases of viral establishment. Further, the host factors contributing to HCV chronicity in a vast majority of acutely HCV-infected individuals largely remain unexplored. The last few years have witnessed a surge in studies showing that HCV adopts myriad mechanisms to disconcert virus-specific immune responses in the host to establish persistence, which includes, but is not limited to viral escape mutations, viral growth at privileged sites, and antagonism. Here we discuss a few hitherto poorly explained mechanisms employed by HCV that are believed to lead to chronicity in infected individuals. A better understanding of these mechanisms would aid the design of improved therapeutic targets against viral establishment in susceptible individuals.