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Conference Paper: Characterization of influenza A viruses with polymorphism in PB2 residues 701 and 702
Title | Characterization of influenza A viruses with polymorphism in PB2 residues 701 and 702 |
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Authors | |
Issue Date | 2018 |
Citation | 2018 World Life Science Conference, Beijing, China, 27-29 October 2018 How to Cite? |
Abstract | The 701 and 702 positions of influenza PB2 polymerase subunit are previously shown to have roles on host range determination. However, limited polymorphisms at these two residues are identified in natural isolates, thereby limiting the study of their role in the polymerase. In this study, we generated 31 different viable viruses by random mutagenesis at this region, indicating that these positions can tolerate a wide range of amino acids. These mutants demonstrated varying polymerase activities and viral replication rates in mammalian and avian cells. Notably, some mutants displayed enhanced polymerase activity, yet their replication kinetics were comparable to the wild-type virus. Surface electrostatic charge predication on the PB2 structural model revealed that the viral polymerase activity in mammalian cells generally increases as this region becomes more positively charged. One of the mutants (701A/702E) showed much reduced pathogenicity in mice while the others had pathogenicity similar to the wild-type level. Distinct tissue tropisms of the PB2-701/702 mutants were observed in infected chicken embryos. Overall, this study demonstrates that the PB2-701/702 region has a high degree of sequence plasticity and sequence changes in this region can alter virus phenotypes in vitro and in vivo. |
Persistent Identifier | http://hdl.handle.net/10722/276167 |
DC Field | Value | Language |
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dc.contributor.author | Chin, WH | - |
dc.contributor.author | Leong, KC | - |
dc.contributor.author | Poon, LML | - |
dc.date.accessioned | 2019-09-10T02:57:20Z | - |
dc.date.available | 2019-09-10T02:57:20Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | 2018 World Life Science Conference, Beijing, China, 27-29 October 2018 | - |
dc.identifier.uri | http://hdl.handle.net/10722/276167 | - |
dc.description.abstract | The 701 and 702 positions of influenza PB2 polymerase subunit are previously shown to have roles on host range determination. However, limited polymorphisms at these two residues are identified in natural isolates, thereby limiting the study of their role in the polymerase. In this study, we generated 31 different viable viruses by random mutagenesis at this region, indicating that these positions can tolerate a wide range of amino acids. These mutants demonstrated varying polymerase activities and viral replication rates in mammalian and avian cells. Notably, some mutants displayed enhanced polymerase activity, yet their replication kinetics were comparable to the wild-type virus. Surface electrostatic charge predication on the PB2 structural model revealed that the viral polymerase activity in mammalian cells generally increases as this region becomes more positively charged. One of the mutants (701A/702E) showed much reduced pathogenicity in mice while the others had pathogenicity similar to the wild-type level. Distinct tissue tropisms of the PB2-701/702 mutants were observed in infected chicken embryos. Overall, this study demonstrates that the PB2-701/702 region has a high degree of sequence plasticity and sequence changes in this region can alter virus phenotypes in vitro and in vivo. | - |
dc.language | eng | - |
dc.relation.ispartof | World Life Science Conferenc, 2018 | - |
dc.title | Characterization of influenza A viruses with polymorphism in PB2 residues 701 and 702 | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Chin, WH: alexchin@hku.hk | - |
dc.identifier.email | Poon, LML: llmpoon@hkucc.hku.hk | - |
dc.identifier.authority | Chin, WH=rp02345 | - |
dc.identifier.authority | Poon, LML=rp00484 | - |
dc.identifier.hkuros | 302392 | - |