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© 2005, 2014 by John Wiley & Sons, Ltd. All rights reserved. The evolution of human hepatitis viruses A, B, C, D, and E (HAV, HBV, HCV, HDV, and HEV, respectively) can be studied over very different time scales. Very rapid sequence change occurs in response to a variety of selection pressures driven by the immune escape from B and T cell responses and immunization and, in treated individuals, by antiviral therapy. Each shows more gradual accumulation of largely neutral nucleotide substitutions that, over a much longer term period, lead ultimately to their differentiation into genetically distinct types. Thus, hepatitis A, B, C, and E viruses are currently divided into 6, 8, 7, and 4 genotypes, respectively, with HCV showing the greatest genetic divergence (>30% nucleotide sequence over the length of the genome) and HBV the least (11-15%). Some hepatitis viruses infect nonhuman primates (NHPs) (HBV and HAV) and other mammals (HEV), while HCV infections are restricted to humans. Sequence variability influences their antigenicity, biology, and host interactions with implications for vaccine development and antiviral therapy.

Original publication





Book title

Viral Hepatitis: Fourth Edition

Publication Date



575 - 586