Specific mutations in the 2B and 2C genes of the hepatitis A virus synergistically enhance its ability to grow in cell culture.
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May inform attenuated HAV vaccine design; extends 2B/2C mutation mechanisms but leaves open in vivo relevance.
Oligonucleotide-directed mutagenesis of an infectious cDNA clone of wild-type hepatitis A virus was performed to determine which mutations acquired in the nonstructural 2B and 2C genes during adaptation to growth in cell culture were effective in enhancing virus growth in vitro. Results of transfection assays demonstrated that one mutation in the 2B gene and two mutations in the 2C gene were responsible for an increased efficiency in growth, but growth enhancement required the participation of at least two of the three mutations.
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Emerson et al. (1992) studied this question.
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