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Importance of amino acid 216 in nonstructural protein 2B for replication of hepatitis A virus in cell culture and in vivo
Author(s) -
Graff Judith,
Emerson Suzanne U.
Publication year - 2003
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.10457
Subject(s) - virology , biology , virus , viral replication , cell culture , in vivo , mutant , amino acid , gene , genetics
Clinical isolates of hepatitis A virus (HAV) replicate inefficiently in cell culture unless mutations are acquired throughout the genome. An Ala‐to‐Val substitution in the nonstructural protein 2B (2B‐216) was known to have a major impact on replication in cell culture. Analysis of chimeric viruses confirmed that the 2B‐A[216]V change was critical for efficient replication and that Leu or Ile could substitute for Val. Viruses containing Val, Ile, or Leu at 2B‐216 all replicated with similar kinetics in cell culture, whereas the virus containing Ala at this position grew 10‐ to 20‐fold less efficiently. In contrast, in vivo, virus with either Ala or Val at 2B‐216 replicated equally efficiently when tested in a chimpanzee and in tamarins, and each amino acid was stably maintained. Attempts to complement wild‐type 2B in trans with adapted 2B provided by co‐infection with a second viable HAV mutant failed to enhance replication of the virus containing the wild‐type 2B sequence. J. Med. Virol. 71:7–17, 2003. © 2003 Wiley‐Liss, Inc.