Journal
VIROLOGY
Volume 401, Issue 1, Pages 96-106Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2010.01.036
Keywords
H5N1; Influenza A/duck/Fujian/01/2002; Influenza A/duck/Guangxi/53/2002; RNA polymerase; PA subunit; PB2 subunit; Replication
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Funding
- Croucher post-doctoral Fellowship
- MRC [G9523972, G9901312]
- Chinese National Natural Science Foundation [30825032]
- Medical Research Council [G9523972] Funding Source: researchfish
- MRC [G9523972] Funding Source: UKRI
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The influenza RNA polymerase is known to be important in pathogenicity and adaptation of avian influenza viruses to mammalian hosts. However, the molecular mechanisms responsible are only partly understood. Here we investigated the role of the polymerase in two different, closely related, H5N1 influenza viruses - a high pathogenic, A/duck/Fujian/01/2002 (FJ) strain and a low pathogenic, A/duck/Guangxi/53/2002 (GX) strain. The polymerase activity of the FJ strain was significantly greater than the GX strain. Experiments with hybrid polymerase constructs - both in vitro and in ribonucleoprotein cell-based assays, suggested that the PA and to a lesser extent the PB2 subunits of the polymerase, were responsible for increased polymerase activity of the high pathogenic strain. However, promoter binding was inversely correlated with polymerase activity implying that excessive promoter binding inhibited polymerase activity by preventing promoter clearance. Overall, we suggest that the influenza polymerase is one of the determinants of pathogenicity of duck H5N1 viruses. (C) 2010 Elsevier Inc. All rights reserved.
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