For a ubiquitous, low pathogenic, and seemingly innocuous avian flu virus - one that rarely infects, and mildly sickens humans - we spend an awful lot of time looking at, and trying to analyze, avian H9N2.
But it is not without good reason, for H9N2 has shared its internal genes with - and thereby helped to create - some of the most dangerous avian flu viruses (H5N1, H7N9, H10N8) on the planet.
While LPAI on its own, H9N2 is so enmeshed in the growing constellation HPAI viruses that I've taken to calling the Professor Moriarty of avian flu viruses. Often, when new HPAI flu strains emerge – if you look deep enough – you’ll find LPAI H9N2 was skulking somewhere in the shadows.
Last November in PLoS Path: Genetics, Receptor Binding, and Transmissibility Of Avian H9N2 researchers found evidence of Chinese H9N2 viruses binding preferentially to alpha 2,6 receptor cells - the type commonly found in the human upper respiratory tract - rather than to alpha 2,3 receptor cells which are found in the gastrointestinal tract of birds.
Previously we've looked at H9N2's propensity to reassort with other avian flu viruses (see PNAS: Reassortment Of H1N1 And H9N2 Avian viruses & PNAS: Reassortment Potential Of Avian H9N2) which have demonstrated H9N2's ability of producing `biologically fit’ and highly pathogenic reassortant viruses.
More recently, in early 2014 The Lancet carried a report entitled Poultry carrying H9N2 act as incubators for novel human avian influenza viruses where researchers warned that `reassortment between the prevalent poultry H9N2 viruses (providing genetic segments) and the influenza virus from wild birds could make the influenza evolve to adapt to domestic hosts.'
Also last November, in EID Journal: Replication Of Avian H9N2 In Pet Birds, Chickens, and Mammals, Bangladesh we looked at just how promiscuous (and successful) this avian virus has become - both on its own, and lending bits and pieces of its genetic structure to other viruses.
As we've seen with other widely distributed avian flu viruses, H9N2 has evolved into many different clades.
The virus you get in Bangladesh is quite distinct from the version you’ll find in China, or the Middle East. The Bangladeshi virus is a novel reassortant (with avian H7N3) that has acquired some mammalian adaptations along the way, making this strain of particular interest to study.
All of which serves as prelude to a new study appearing in Nature's Emerging Microbes and Infections - with a pedigree that includes Robert G. Webster and Richard J. Webby - that looks at the evolution, and replication of Bangladeshi H9N2 in human bronchoepithelial cells, swine lung & tracheal explants, Balb/c mice, and ferrets.
This study finds that these viruses have the potential to infect humans but currently lack transmission potential, limiting their threat to human health. They do, however, continue to evolve and reassort with other viruses, making it vital that we continue to monitor them closely.
It is a long, detailed, open access study, so you'll want to follow the link to read it in its entirety.
Karthik K Shanmuganatham1, Jeremy C Jones1, Bindumadhav M Marathe1, Mohammed M Feeroz2, Lisa Jones-Engel3, David Walker1, Jasmine Turner1, S M Rabiul Alam2, M Kamrul Hasan2, Sharmin Akhtar2, Patrick Seiler1, Pamela McKenzie1, Scott Krauss1, Richard J Webby1 and Robert G Webster1
- 1Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105, USA
- 2Department of Zoology, Jahangirnagar University, Dhaka 1342, Bangladesh
- 3National Primate Research Center University of Washington, Seattle, WA 98195-5502, USACorrespondence: RG Webster, E-mail: email@example.comReceived 3 November 2015; Revised 29 December 2015; Accepted 6 January 2016
ABSTRACTH9N2 avian influenza viruses are continuously monitored by the World Health Organization because they are endemic; they continually reassort with H5N1, H7N9 and H10N8 viruses; and they periodically cause human infections.We characterized H9N2 influenza viruses carrying internal genes from highly pathogenic H7N3 viruses, which were isolated from chickens or quail from live-bird markets in Bangladesh between 2010 and 2013. All of the H9N2 viruses used in this study carried mammalian host-specific mutations.We studied their replication kinetics in normal human bronchoepithelial cells and swine tracheal and lung explants, which exhibit many features of the mammalian airway epithelium and serve as a mammalian host model.
All H9N2 viruses replicated to moderate-to-high titers in the normal human bronchoepithelial cells and swine lung explants, but replication was limited in the swine tracheal explants. In Balb/c mice, the H9N2 viruses were nonlethal, replicated to moderately high titers and the infection was confined to the lungs.
In the ferret model of human influenza infection and transmission, H9N2 viruses possessing the Q226L substitution in hemagglutinin replicated well without clinical signs and spread via direct contact but not by aerosol.None of the H9N2 viruses tested were resistant to the neuraminidase inhibitors. Our study shows that the Bangladeshi H9N2 viruses have the potential to infect humans and highlights the importance of monitoring and characterizing this influenza subtype to better understand the potential risk these viruses pose to humans.