Partial characterization of hepatitis A viruses from three intermediate passage levels of a series resulting in adaptation to growth in cell culture and attenuation of virulence

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Abstract
Viruses from passages 9/10, 21, and 32 of a serially passaged human isolate of hepatitis A virus, strain HM-175, were partially sequenced and compared for their abilities to grow in cell cultures and to cause disease in primates. Viruses from all passages grew more efficiently in cell culture than did the wild-type virulent virus from which they were derived, and all displayed some degree of attenuation of virulence for primates. Within the 5' noncoding region and the 2B2C region of the HAV genome, passage 9/10 virus differed in sequence from wild-type at a single and novel position in the 2C gene, while the sequence of the passage 32 virus was almost identical to that of a fully attenuated passage 35 virus. Passage 21 viruses were found to consist of a mixture of viruses which included all but two of the 13 mutations present in the sequenced regions of the virus from passage 32.