Abstract
H9N2 subtype avian influenza viruses (AIVs) have shown expanded host range and can infect mammals, such as humans and swine. To date the mechanisms of mammalian adaptation and interspecies transmission of H9N2 AIVs remain poorly understood. To explore the molecular basis determining mammalian adaptation of H9N2 AIVs, we compared two avian field H9N2 isolates in a mouse model: one (A/chicken/Guangdong/TS/2004, TS) is nonpathogenic, another one (A/chicken/Guangdong/V/2008, V) is lethal with efficient replication in mouse brains. In order to determine the basis of the differences in pathogenicity and brain tropism between these two viruses, recombinants with a single gene from the TS (or V) virus in the background of the V (or TS) virus were generated using reverse genetics and evaluated in a mouse model. The results showed that the PB2 gene is the major factor determining the virulence in the mouse model although other genes also have variable impacts on virus replication and pathogenicity. Further studies using PB2 chimeric viruses and mutated viruses with a single amino acid substitution at position 627 [glutamic acid (E) to lysine, (K)] in PB2 revealed that PB2 627K is critical for pathogenicity and viral replication of H9N2 viruses in mouse brains. All together, these results indicate that the PB2 gene and especially position 627 determine virus replication and pathogenicity in mice. This study provides insights into the molecular basis of mammalian adaptation and interspecies transmission of H9N2 AIVs.
Highlights
Since the first H9N2 subtype avian influenza virus (AIV) was isolated from turkeys in 1966 in the U.S [1], this subtype of viruses has been circulating in birds worldwide
The diseased or dead chickens in the farms with an outbreak of respiratory disease were most likely caused by multiple pathogens rather than a single H9N2 influenza virus according to the Intravenous Pathogenicity Index (IVPI) test
These findings indicate that some H9N2 isolates have expanded their host range and have adapted to mammalian hosts
Summary
Since the first H9N2 subtype avian influenza virus (AIV) was isolated from turkeys in 1966 in the U.S [1], this subtype of viruses has been circulating in birds worldwide. H9N2 viruses are often found in shorebirds and wild ducks in North America [2], there is no evidence of a permanent lineage of these viruses in land-based poultry [3]. Further evidence of its mammalian host range is that some H9N2 strains replicate efficiently in mice and are able to kill mice without prior adaptation [5,18]. All these facts indicate that H9N2 AIVs have expanded their host range and are able to infect different mammalian hosts including humans
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
