title: Report of novel H105R, D29N, V27A mutations in the methyltransferase region of the HEV genome in patients with acute liver failure.
abstract: The Hepatitis E virus (HEV) has been responsible for major outbreaks in the developing countries affecting millions of people and acute sporadic hepatitis worldwide. The HEV methyltransferase is important for capping the 5'-end of the viral pregenomic RNA which is critical for viral infection.
  
  
  
  We aimed to assess the substitutional profile in the HEV methyltransferase region in patients with acute liver failure (ALF) and acute viral hepatitis (AVH) from North Indian population and associate the substitutions with the poor outcome of the disease.
  
  
  
  HEV RNA was detected and partial region encoding the Methyltransferase domain in the HEV genome was amplified by Reverse Transcriptase(RT-PCR). Viral load of HEV was quantified utilizing Real time PCR.32 representative samples consisting of 16 AVH and 16 ALF were directly sequenced and amino acid changes were compared using Fischer's exact (two-tailed) test.
  
  
  
  Novel mutations Valine27Alanine (V27A), Aspartate29Asparagine (D29N) and Histidine105Arginine (H105R) mutation corresponding to 107T>C, 115G>A and 341 A>G substitutions respectively were significantly (p<0.0001) obtained in 16/16(100%) ALF patients compared to none (0/16) of the AVH patients. HEV viral load and disease severity parameters corresponding to the samples with D29N and V27A mutations were significantly higher compared to the isolates lacking these mutations while the H105R mutation was associated with decreased viremia.
  
  
  
  The D29N and V27A mutations had significant association with the poor outcome in ALF patients suggesting key role in enhancing HEV replication while the association of H105R mutation with decreased viremia creates interest on its antiviral aspects.
authors.affiliation: PCR Hepatitis Laboratory, Department of Medicine, Maulana Azad Medical College, University of Delhi, New Delhi, India; Department of Biotechnology, Gauhati University, Assam, India.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Borkakoti
authors.affiliation: Department of Biotechnology, Gauhati University, Assam, India.
authors.forename: Giasuddin
authors.initials: G
authors.lastname: Ahmed
authors.affiliation: Department of Biochemistry, National Centre for Disease Control, New Delhi, India.
authors.forename: Arvind
authors.initials: A
authors.lastname: Rai
authors.affiliation: PCR Hepatitis Laboratory, Department of Medicine, Maulana Azad Medical College, University of Delhi, New Delhi, India. Electronic address: borkakoti.jayanta@gmail.com.
authors.forename: Premashis
authors.initials: P
authors.lastname: Kar
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D016679:Genome, Viral; D016751:Hepatitis E / Q000097:blood / Q000453:epidemiology / Q000401:mortality / Q000821:virology*; D016752:Hepatitis E virus / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D017114:Liver Failure, Acute / Q000821:virology; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology; D012367:RNA, Viral / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012698:Serologic Tests; D019562:Viral Load / Q000379:methods; D014766:Viremia / Q000453:epidemiology; D055815:Young Adult
chemical_list: D012367:RNA, Viral; D008780:Methyltransferases
keywords: Acute liver failure; D29N; H105R; HEV; Methyltransferase; V27A