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Hepatitis E virus from India exhibits significant amino acid mutations in fulminant hepatic failure patients

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Abstract

In India, hepatitis E virus (HEV) is the predominant cause of acute viral hepatitis (AVH) and fulminant hepatic failure (FHF) among pregnant women and adults. The present study evaluates association, if any, of the mutations in the viral genome with disease outcome. Ten genotype-1 complete genomes (five each from AVH and FHF patients) were sequenced. Phylogenetic analysis showed a distinct cluster including all five FHF–HEV sequences from western India (present study), one FHF isolate from northern India, and one AVH isolate detected in 2010 (present study). HEV genotype-1 sequences from fulminant cases exhibited 150 significantly different (p ≤ 0.05) nucleotide substitutions when compared to all genotype-1-AVH sequences as well as isolates from the Indian subcontinent. At six positions, all FHF sequences showed identical substitutions (1 non-synonymous). Six amino acid changes in ORF1; F179S, A317T, T735I, L1110F, V1120I, and F1439Y were significantly associated with HEV-type-1 FHF. The data suggests that the nucleotide substitutions recorded and/or L1110F and V1120I amino acid substitutions in helicase domain may play important role in determining outcome of HEV infection.

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Abbreviations

HEV:

Hepatitis E virus

AVH:

Acute viral hepatitis

FHF:

Fulminant hepatic failure

ORF:

Open reading frame

TNF-α:

Tumor necrosis factor-alpha

IFN-γ:

Interferon-gamma

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Acknowledgments

The authors thank Dr Mishra AC, Director NIV for all the support. We gratefully acknowledge financial support provided by ICMR, Ministry of Health and Family Welfare, Government of India. Nischay Mishra acknowledges CSIR for providing Senior Research Fellowship.

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Authors and Affiliations

  1. Hepatitis Group, National Institute of Virology, 130/1, Sus Road, Pashan, Pune, 411021, Maharashtra, India

    Nischay Mishra, Atul M. Walimbe & Vidya A. Arankalle

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  1. Nischay Mishra
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  2. Atul M. Walimbe
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  3. Vidya A. Arankalle
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Correspondence to Vidya A. Arankalle.

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Mishra, N., Walimbe, A.M. & Arankalle, V.A. Hepatitis E virus from India exhibits significant amino acid mutations in fulminant hepatic failure patients. Virus Genes 46, 47–53 (2013). https://doi.org/10.1007/s11262-012-0833-7

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  • DOI: https://doi.org/10.1007/s11262-012-0833-7

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