Journal
JOURNAL OF VIROLOGY
Volume 85, Issue 18, Pages 9641-9645Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00702-11
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Funding
- National Institute of Allergy and Infectious Diseases (NIAID) [HHSN26600700005C]
- Area of Excellence of the University Grants Commission of the Hong Kong SAR Government [AoE/M-12/06]
- Research Grants Council, Hong Kong SAR Government [HKU 7612/08 M]
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We investigated the tropism, host responses, and virulence of two variants of A/Quail/Hong Kong/G1/1997 (H9N2) (H9N2/G1) with D253N and Q591K in the PB2 protein in primary human macrophages and bronchial epithelium in vitro and in mice in vivo. Virus with PB2 D253N and Q591K had greater polymerase activity in minireplicon assays, induced more tumor necrosis factor alpha (TNF-alpha) in human macrophages, replicated better in differentiated normal human bronchial epithelial (NHBE) cells, and was more pathogenic for mice. Taken together, our studies help define the viral genetic determinants that contribute to pathogenicity of H9N2 viruses.
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