tetano
Editor, Senior Moderator
Virology. 2014 Sep 25;468-470C:545-555. doi: 10.1016/j.virol.2014.09.008. [Epub ahead of print]
Influenza A viruses with different amino acid residues at PB2-627 display distinct replication properties in vitro and in vivo: Revealing the sequence plasticity of PB2-627 position.
Chin AW1, Li OT1, Mok CK2, Ng MK1, Peiris M2, Poon LL3.
Author information
Abstract
Sequence analyses of influenza PB2 sequences indicate that the 627 position almost exclusively contains either lysine (K) or glutamic acid (E), suggesting a high sequence constraint at this genetic marker. Here, we used a site-directed random mutagenesis method to demonstrate that PB2-627 position has a high sequence plasticity. Recombinant viruses carrying various amino acid residues at this position are viable in cell cultures. These PB2-627 mutants showed various polymerase activities and replication kinetics in mammalian and avian cells as well as pathogenicity in mice. Serially passaging these mutants in MDCK cells generated some compensatory PB2 mutations that can restore polymerase activities of the PB2-627 mutants. Of these, PB2-D309N was identified as a novel one. Besides showing that influenza virus can tolerate a wide range of amino acid residues at the PB2-627 position, this study also demonstrates a potential strategy to identify novel mutations that can enhance viral polymerase.
Copyright ? 2014 Elsevier Inc. All rights reserved.
KEYWORDS:
Influenza; PB2; PB2-627; Polymerase; Random mutagenesis
PMID:
25262472
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25262472
Influenza A viruses with different amino acid residues at PB2-627 display distinct replication properties in vitro and in vivo: Revealing the sequence plasticity of PB2-627 position.
Chin AW1, Li OT1, Mok CK2, Ng MK1, Peiris M2, Poon LL3.
Author information
Abstract
Sequence analyses of influenza PB2 sequences indicate that the 627 position almost exclusively contains either lysine (K) or glutamic acid (E), suggesting a high sequence constraint at this genetic marker. Here, we used a site-directed random mutagenesis method to demonstrate that PB2-627 position has a high sequence plasticity. Recombinant viruses carrying various amino acid residues at this position are viable in cell cultures. These PB2-627 mutants showed various polymerase activities and replication kinetics in mammalian and avian cells as well as pathogenicity in mice. Serially passaging these mutants in MDCK cells generated some compensatory PB2 mutations that can restore polymerase activities of the PB2-627 mutants. Of these, PB2-D309N was identified as a novel one. Besides showing that influenza virus can tolerate a wide range of amino acid residues at the PB2-627 position, this study also demonstrates a potential strategy to identify novel mutations that can enhance viral polymerase.
Copyright ? 2014 Elsevier Inc. All rights reserved.
KEYWORDS:
Influenza; PB2; PB2-627; Polymerase; Random mutagenesis
PMID:
25262472
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25262472