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Journal of Clinical Microbiology, December 2002, p. 4493-4498, Vol. 40, No. 12
0095-1137/02/$04.00+0     DOI: 10.1128/JCM.40.12.4493-4498.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Evidence that Rodents Are a Reservoir of Hepatitis E Virus for Humans in Nepal

Junkun He,¹ Bruce L. Innis,^1, Mrigendra P. Shrestha,² Edward T. Clayson,^3, Robert M. Scott,² Kenneth J. Linthicum,^3,3 Guy G. Musser,⁴ Scott C. Gigliotti,³ Leonard N. Binn,¹ Robert A. Kuschner,¹ and David W. Vaughn^1*

Walter Reed Army Institute of Research, Silver Spring, Maryland,¹ Walter Reed Army Institute of Research/Armed Forces Research Institute of Medical Sciences Research Unit—Nepal, Kathmandu, Nepal,² Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand,³ American Museum of Natural History, New York, New York⁴

Received 21 May 2002/ Returned for modification 7 August 2002/ Accepted 30 August 2002

Hepatitis E virus (HEV) is an important cause of enterically transmitted hepatitis in developing countries. Sporadic autochthonous cases of hepatitis E have been reported recently in the United States and other industrialized countries. The source of HEV infection in these cases is unknown; zoonotic transmission has been suggested. Antibodies to HEV have been detected in many animals in areas where HEV is endemic and in domestic swine and rats in the United States. There is evidence supporting HEV transmission between swine and humans. Nevertheless, HEV has not been detected in wild rodents. We tested murid rodents and house shrews trapped in Nepal's Kathmandu Valley, where hepatitis E is hyperendemic, for HEV infection. The most commonly trapped species was Rattus rattus brunneusculus. Serum samples from 675 animals were tested for immunoglobulin G against HEV by enzyme-linked immunosorbent assay; 78 (12%) were positive, indicating acute or past infection. Antibody prevalence was higher among R. rattus brunneusculus and Bandicota bengalensis than in Suncus murinus. Forty-four specimens from 78 antibody-positive animals had sufficient residual volume for detection of HEV RNA (viremia) by reverse transcription-PCR. PCR amplification detected four animals (9%; three were R. rattus brunneusculus and one was B. bengalensis) with viremia. Phylogenetic analysis of the four genome sequences (405 bp in the capsid gene) recovered showed that they were identical, most closely related to two human isolates from Nepal (95 and 96% nucleotide homology, respectively), and distinct from HEV sequences isolated elsewhere. These data prove that certain peridomestic rodents acquire HEV in the wild and suggest that cross-species transmission occurs, with rodents serving as a virus reservoir for humans.

Present address: Clinical Research and Development and Medical Affairs, Vaccines, GlaxoSmithKline, Collegeville, PA 19426.

Present address: Joint Program Office for Biological Defense, Falls Church, VA 22041-3203.

Present address: Vector-Borne Disease Section, Southern Region, California Department of Health Services, Ontario, CA 91764.

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