Epidemiology and Infection

Hepatitis

Genetic analysis of precore/core and partial pol genes in an unprecedented outbreak of fulminant hepatitis B in India

S. KHAREa1, S. S. NEGIa2, S. SINGHa1a2, M. SINGHALa2, S. KUMARa2, C. PRAKASHa1, R. VENUGOPALa2, D. S. RAWATa2, L. S. CHAUHANa1a2 and A. RAIa2 c1

a1 Viral Hepatitis Laboratory, Division of Microbiology, National Centre for Disease Control (NCDC), Delhi, India

a2 Molecular Virology Laboratory, Division of Biotechnology, National Centre for Disease Control (NCDC), Delhi, India

SUMMARY

We investigated an unprecedented outbreak of fulminant hepatitis B virus (HBV) that occurred in Modasa, Gujarat (India) in 2009. Genomic analysis of all fulminant hepatic failure cases confirmed exclusive predominance of subgenotype D1. A1762T, G1764A basal core promoter (BCP) mutations, insertion of isoleucine after nt 1843, stop codon mutation G1896A, G1862T transversion plus seven other mutations in the core gene caused inhibition of HBeAg expression implicating them as circulating precore/BCP mutant virus. Two rare mutations at amino acids 89 (Ile→Ala) and 119 (Leu→Ser) in addition to other mutations in the polymerase (pol) gene may have caused some alteration in either of four pol gene domains to affect encapsidation of pregenomic RNA to enhance pathogenicity. Sequence similarity among patients' sequences suggested an involvement of a single hepatitis B mutant strain/source to corroborate the finding of gross and continued usage of HBV mutant-contaminated syringes/needles by a physician which resulted in this unprecedented outbreak of fulminant hepatitis B. The fulminant exacerbation of the disease might be attributed to mutations in the BCP/precore/core and pol genes that may have occurred due to selection pressure during rapid spread/mutation of the virus.

(Received December 23 2011)

(Revised February 03 2012)

(Accepted February 13 2012)

(Online publication March 15 2012)

Correspondence:

c1 Author for correspondence: Dr A. Rai, Ph.D., Joint Director & Head, Division of Biochemistry & Biotechnology, National Centre for Disease Control (NCDC), 22-Sham Nath Marg, Delhi-110054, India. (Email: arvindrai_16@hotmail.com)

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