Ubiquitin-like protein modifiers and their potential for antiviral and anti-HCV therapy

Abstract

All viral infections subvert the host immune response. Targeting the host mechanisms that are modulated by viral infection offers new avenues for antiviral drug development. Host ubiquitin and multiple ubiquitin-like modifiers (Ubls) are commonly altered by, or important for, viral infection. Protein modification by ubiquitin or Ubls contributes to numerous cellular processes, such as protein degradation, signal transduction, protein relocalization and pathogen–host interactions. This post-translational modification plays an essential role for viral life cycles and host antiviral mechanisms. Some Ubls, such as ISG15 and SUMO, have been shown to modulate virus infections and are potential targets for therapeutic manipulation. Hepatitis C virus (HCV) is a positive-stranded RNA virus that predominantly infects hepatocytes. Recent data suggest that ISG15 might be a potential drug target for anti-HCV therapy. Inhibition of ISG15 expression and/or ISG15 conjugation (ISGylation) provides a rationale for the design of new anti-HCV drugs.

Keywords::

• direct-acting antivirals
• HCV
• interferon-stimulated genes
• post-translational modification
• protease inhibitors
• ubiquitin
• ubiquitin-like modifiers

Financial & competing interests disclosure

The authors have received financial support from the Sichuan provincial science and technology department (2011SZ0010 to L Chen and 2013JY0048 to S Li) via the Institute of Blood Transfuision, Chinese Academy of Medical Sciences and Peking Union College. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript