Hepatitis E Virus Mutations: Functional and Clinical Relevance

• Published in: EBioMedicine 2016-09, Vol.11 (C), p.31-42
• Main Authors: van Tong, Hoang, Hoan, Nghiem Xuan, Wang, Bo, Wedemeyer, Heiner, Bock, C.-Thomas, Velavan, Thirumalaisamy P.
• Format: Article
• Language: English
• Subjects: Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Genetic Variation; Genome, Viral; Genotype; Hepatitis E - diagnosis; Hepatitis E - drug therapy; Hepatitis E - etiology; Hepatitis E - prevention & control; Hepatitis E virus; Hepatitis E virus - classification; Hepatitis E virus - drug effects; Hepatitis E virus - physiology; HEV infection; HEV mutation; HEV replication; HEV treatment failure; HEV variability; Humans; Mutation; Open Reading Frames; Recombination, Genetic; Review; RNA, Viral; Viral Vaccines - genetics; Viral Vaccines - immunology; Virus Replication
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2016.07.039

Hepatitis E virus (HEV) infection is a major cause of acute hepatitis and affects more than 20 million individuals, with three million symptomatic cases and 56,000 recognized HEV-related deaths worldwide. HEV is endemic in developing countries and is gaining importance in developed countries, due to increased number of autochthone cases. Although HEV replication is controlled by the host immune system, viral factors (especially specific viral genotypes and mutants) can modulate HEV replication, infection and pathogenesis. Limited knowledge exists on the contribution of HEV genome variants towards pathogenesis, susceptibility and to therapeutic response. Nonsynonymous substitutions can modulate viral proteins structurally and thus dysregulate virus-host interactions. This review aims to compile knowledge and discuss recent advances on the casual role of HEV heterogeneity and its variants on viral morphogenesis, pathogenesis, clinical outcome and antiviral resistance. •HEV causes acute hepatitis and recently comes into focus because of persistent infection in immunocompromised patients.•HEV variability can be associated with clinical pathogenesis and transmission dynamics.•Mutations in the HEV genome can influence HEV physiology and virus-host interaction.•HEV mutations and variability are likely associated with fulminant hepatic failure and chronic hepatitis E.•The Y1320H and G1634R/K mutations in the RdRp domain contribute to antiviral resistance through enhancing HEV replication. We searched MEDLINE database and PubMed for articles from 1980 through June 30, 2016. Search terms used in various combinations were “hepatitis E”, “hepatitis E virus”, “hepatitis E virus infection”, “hepatitis E virus mutation”, “HEV variability”, “HEV genotype”, “HEV drug resistance”, “HEV replication” and “ribavirin”. Articles resulting from these searches and relevant references cited in those articles were selected based on their related topics and were reviewed. Abstracts and reports from meetings were also included. Articles published in English were included.