The rapid geographic expansion of HPAI and LPAI viruses over the past decade means that there are places where these viruses are co-circulating, reassorting and/or evolving, from which we only get limited surveillance information.
Much of what happens in Sub-Saharan Africa, across large swaths of Asia, and in much of the Middle east go undocumented, leaving many potential places for the next pandemic virus to emerge with little warning.So it's always good when we see some data coming out of these regions, even if the information isn't completely comforting.
Although it isn't the greatest of our pandemic concerns, avian H9N2 occupies a special spot in the bird flu hierarchy since its internal genes make up the backbone of many of the HPAI viruses (including H5N1, H5N6, and H7N9) that pose the greatest risks to both poultry, and human health.
H9N2 can and does (on occasion) infect humans, albeit usually producing only mild to moderate illness. Just a week ago, in Macao Health: Guangdong Province Reports Human H9N2 Infection, we looked at a recent case involving a 24-year old woman from Shenzhen.
Over the past two decades, just over 3 dozen human H9N2 infections have been reported by 3 countries - China, Pakistan & Egypt - (see FluTrackers Global Cumulative H9N2 Partial Case List 1998-2017).
A 2014 seroprevalence study, however, found antibodies against H9N2 ranged from 5.9% to 7.5% among poultry exposed individuals in Egypt, suggesting human infection is far more common than the official numbers would suggest.As far back as 2010 (see Study: The Continuing Evolution Of Avian H9N2) we looked at computer modeling (in silica) that warned the H9N2 virus has been slowly evolving towards becoming a `more humanized’ virus.
While it may well be due to better testing and surveillance, we've seen a decided uptick in reported cases in the past 3 years.All of which brings us to a report, published in Avian Biology Research, which looks at the genetic sequence and phylogenetic description of H9N2 viruses collected from commercial chickens in Iran.
Although our information from that region of the world is limited, we know that HPAI H5N1 returned to Iran after a long absence of reports in 2015, and that HPAI H5N8 arrived in 2016 and expanded its reign in a big way in 2017 (see Iran's Hidden Bird Flu Burden).
In February of this year, learned from the OIE: HPAI H5N6 Arrived In Iran.When you add the highly promiscuous H9N2 virus into the mix . . . well, it's important to learn as much about the avian strains circulating in Iran as possible.
Sequence and phylogenetic analysis of the haemagglutinin genes of H9N2 avian influenza viruses isolated from commercial chickens in Markazi province, Iran
Authors: Saeidi, Hamid Reza; Homayounimehr, Alireza; Hosseini, Seyed Davood; Hosseini, Hossein; Hamidreza, Vaziri
Source: Avian Biology Research, Volume 11, Number 3, August 2018, pp. 173-177(5)
Publisher: Science Reviews 2000 Ltd
Avian influenza viruses of the H9N2 subtype have seriously affected the industry of the Middle East and Asian countries since the 1990s and are considered to be one of the potential candidates for the next human pandemic.
In the present study, to determine the genetic relationship of Iranian viruses, the haemagglutinin (HA) genes from two isolates of H9N2 viruses from commercial chickens in Markazi province (central Iran) during 2013-2014 were amplified and sequenced. Samples were collected and viruses were passed in embryonated hen eggs and virion RNA was extracted from allantoic fluid and reverse transcribed to synthesise cDNA. cDNA was amplified by PCR and the PCR product was purified with a purification kit. Purified fragments were sequenced from both directions. Finally, sequence analysis and phylogenetic studies were conducted by comparing each isolate with those of the available H9N2 strains at Gen Bank.
All of the isolates possessed the same amino acid motif P-A-R-S-S-R/G-L at the HA cleavage site. Amino acid sequence comparisons of HA genes of two isolates showed 93.6% identity. Phylogenetic analysis revealed that all isolates belonged to the G1-like sublineage and one isolate showed some degree of homology with Pakistani isolates.
Two isolates had leucine (L) at position 226 instead of glutamine (Q) which indicated the potential of binding to human-type receptors.
The results of this study suggest that Iranian H9N2 viruses could infect mammalian species, including humans and have the potential to emerge as highly pathogenic influenza viruses in Iran.
The detection of the Q226L amino acid substitution - a mutation that is linked to better mammalian adaptation - is significant, but it isn't unique among H9N2 viruses. In 2016's Genomic Characteristics Of 2 A(H9N2) Virus Isolates From Humans In Anhui Province - 2015, researchers found:
The amino acid sequence alignment results showed that several mutations for human infection tropism presented in the two virus strains, including Q226L, H183N and E190T in HA; S31N in M2; 63-65 deletion in NA. In addition, the H9N2 influenza virus strains possessed the PSRSSR\GL motif in HA.While in 2015, in EID Journal: Replication Of Avian H9N2 In Pet Birds, Chickens, and Mammals, Bangladesh, scientists reported:
The H9N2 virus strain Env/9306 contains mammalian-like mutations in genes, including HAQ226L (H3 numbering) (5), which increase H9N2 virus transmissibility to and among mammals.And just last year, in Three Mutations That Switch H7N9 To Human-type Receptor Specificity, G228S and Q226L were both called out at being instrumental in changing H7N9 into a more humanized virus.
The majority of human H7N9 isolates contained a hemagglutinin (HA) mutation (Q226L) that has previously been associated with a switch in receptor specificity from avian-type (NeuAcα2-3Gal) to human-type (NeuAcα2-6Gal), as documented for the avian progenitors of the 1957 (H2N2) and 1968 (H3N2) human influenza pandemic viruses.And as the above passage notes, the Q226L mutation has previously been linked to the emergence of human pandemic strains. For a more in-depth look, you may wish to visit JVI's Role of Substitutions in the Hemagglutinin in the Emergence of the 1968 Pandemic Influenza Virus.
While H9N2 is nowhere near the top of our pandemic threats list it is regarded as having at least some pandemic potential (see CDC IRAT SCORE), and several candidate vaccines have been developed over the years.
And as we've seen previously in China, Bangladesh, and now in Iran - H9N2 appears to be continuing along an evolutionary path which could potentially lead it to better mammalian adaptation.Making H9N2 a virus very much worth keeping an eye on.