Report of a novel C1483W mutation in the hepatitis E virus polymerase in patients with acute liver failure.
Here, we report the molecular alterations in the HEV genome from patients with acute liver failure (ALF) and acute viral hepatitis (AVH) from North India, including pregnant women and its association with the poor outcome of the disease. We partially sequenced the RNA Dependent RNA polymerase (RdRp) region of the ORF 1 protein in the HEV genome from representative samples from patients with ALF and AVH and identified two novel mutations Cysteine 1483 Tryptophan and Asparagine 1530 Threonine in 100% (25/25) of the patients with ALF compared to none (0/30) of the patients with AVH (P<0.0001). Disease severity parameters along with viral load corresponding to the samples with C1483W and N1530T mutations were significantly higher compared to those lacking the mutation showing significant association with the outcome in ALF patients. The nucleotide substitutions in the RdRp region may play a crucial role in enhancing HEV replication thus leading to disease severity.
PCR Hepatitis Laboratory, Department of Medicine, Maulana Azad Medical College, University of Delhi, New Delhi, India; Department of Biotechnology, Gauhati University, Assam, India.
Jayanta
J
Borkakoti
Department of Biotechnology, Gauhati University, Assam, India.
Giasuddin
G
Ahmed
PCR Hepatitis Laboratory, Department of Medicine, Maulana Azad Medical College, University of Delhi, New Delhi, India. Electronic address: borkakoti.jayanta@gmail.com.
Premashis
P
Kar
D000328:Adult; D005260:Female; D016679:Genome, Viral; D016751:Hepatitis E / Q000150:complications* / Q000209:etiology / Q000821:virology; D016752:Hepatitis E virus / Q000235:genetics*; D006801:Humans; D007194:India; D017114:Liver Failure, Acute / Q000209:etiology / Q000821:virology*; D009154:Mutation; D016366:Open Reading Frames; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics*; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics
D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase
Acute liver failure; Mutation; RNA Dependent RNA polymerase