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Journal of Virology, September 2002, p. 8551-8559, Vol. 76, No. 17
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.17.8551-8559.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Identification of VP1/2A and 2C as Virulence Genes of Hepatitis A Virus and Demonstration of Genetic Instability of 2C

Suzanne U. Emerson,1* Ying K. Huang,1 Hanh Nguyen,1 Alicia Brockington,1 Sugantha Govindarajan,2 Marisa St. Claire,3 Max Shapiro,3 and Robert H. Purcell4

Molecular Hepatitis,1 Hepatitis Viruses Sections, Laboratory of Infectious Diseases, National Institute of AllergyInfectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-8009,4 Liver Research Laboratory, Rancho Los Amigos Medical Center, Downey, California 90242,2 Bioqual, Inc., Rockville, Maryland 208503

Received 28 February 2002/ Accepted 3 June 2002

Fourteen different chimeric virus genomes were constructed from two infectious cDNA clones encoding a virulent and an attenuated isolate, respectively, of the HM175 strain of hepatitis A virus. The ability of each recombinant virus to infect tamarins and to cause acute hepatitis was determined. Comparisons of the genotype and phenotype of each virus suggested that VP1/2A and 2C genes were responsible for virulence. The 2C gene derived from the attenuated parent virus was unstable, and one or more mutations arose in this gene during the first passage in tamarins.

* Corresponding author. Mailing address: Bldg. 50, Room 6537, 50 South Dr., MSC-8009, Bethesda, MD 20892-8009. Phone: (301) 496-2787. Fax: (301) 402-0524. Email: semerson{at}niaid.nih.gov.

Journal of Virology, September 2002, p. 8551-8559, Vol. 76, No. 17
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.17.8551-8559.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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