Tuesday, November 12, 2019

Viruses: Characterization of the H9N2 Avian Influenza Viruses Currently Circulating in South China

Flu Virus binding to Receptor Cells – Credit CDC


For a relatively innocuous avian flu virus - one that is only rarely reported to sicken humans, and generally produces only mild-to-moderate symptoms - we spend an awful lot of time looking at, and trying to analyze, avian H9N2.

But it is not without cause. 
While H9N2 may not be at the very top of our pandemic threats list, it is still regarded as having at least some pandemic potential (see CDC IRAT SCORE), and several candidate vaccines have been developed

And in recent years, evidence has suggested H9N2's pandemic potential has been increasing, as the virus continues to evolve, reassort, and adapt. A few recent blogs include:
OFID: Avian H5, H7 & H9 Contamination Before & After China's Massive Poultry Vaccination Campaign
Macao MOH Notified Of H9N2 Case In Jiangsu Province
J. Virology:Genetic Compatibility of Reassortants Between Avian H5N1 & H9N2 Influenza Viruses

Virology: Receptor Binding Specificity Of H9N2 Avian Influenza Viruses

EID Journal: Two H9N2 Studies Of Note

All of which brings us to a new study, published in the journal Viruses, that finds that China's current crop of H9N2 viruses continues on an evolutionary path that increases its pandemic potential.

First some excerpts from a much longer report, after which I'll return with a postscript. Follow the link to read the study in its entirety. 

Viruses 2019, 11(11), 1040; https://doi.org/10.3390/v11111040

Genetic, Molecular, and Pathogenic Characterization of the H9N2 Avian Influenza Viruses Currently Circulating in South China
by Hailiang Sun †, Jiate Lin †, Zhiting Liu, Yanan Yu, Meihua Wu, Shuo Li, Yang Liu, Yaling Feng, Yuqian Wu, Mingliang Li, Peirong Jiao, Kaijian Luo and Ming Liao *

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China

Received: 28 August 2019 / Accepted: 6 November 2019 / Published: 8 November 2019 


The prevalence and variation of the H9N2 avian influenza virus (AIV) pose a threat to public health. A total of eight viruses isolated from farmed poultry in South China during 2017–2018 were selected as representative strains for further systematic study. 

Phylogenetic analyses indicated that these prevalent viruses belong to the Y280-like lineage and that the internal genes are highly similar to those of recently circulating human H7N9 viruses.
The receptor-binding assay showed that most of the H9N2 isolates preferentially bound to the human-like receptor, increasing the risk of them crossing the species barrier and causing human infection.

Our in vitro, multi-step growth curve results indicate these viruses can effectively replicate in mammalian cells. Infection in mice showed that three viruses effectively replicated in the lung of mice. Infection in swine revealed that the viruses readily replicated in the upper respiratory tract of pig and effectively induced viral shedding.

Our findings suggested that the H9N2 AIVs circulating in poultry recently acquired an enhanced ability to transmit from avian to mammalians, including humans. Based on our findings, we propose that it is essential to strengthen the efforts to surveil and test the pathogenicity of H9N2 AIVs.
Taken together, a novel H9N2 genotype recently circulating in poultry preferentially bound to the human receptor and acquired multiple mutations adaptive to mammals. Efforts to strengthen the surveillance of H9N2 AIVs and illuminate their pathogenicity are urgently needed to assess the potential risk of H9N2 AIVs to public health.

(Continue . . . )

The most recent CDC IRAT analysis (conducted in 2014) estimates the risk of emergence, and the potential health impact, of an H9N2 pandemic as moderate, based on samples collected and tested in 2011. 
H9N2: Avian H9N2 G1 lineage [A/Bangladesh/0994/2011]

Human infections with influenza A(H9N2) virus have been reported sporadically, cases reportedly exhibited mild influenza-like illness. Historically, these low pathogenicity avian influenza viruses have been isolated from wild and domestic birds. In response to these reports, a risk assessment of this H9N2 influenza virus was conducted in 2014.

Summary: The summary average risk score for the virus to achieve sustained human-to-human transmission was in the moderate risk category (less than 6). The summary average risk score for the virus to significantly impact public health if it were to achieve sustained human-to-human transmission also fell in the moderate risk range (less than 6).
The viruses (collected in 2017-2018) for today's study belong to a Y280-like lineage, and so its threat profile may differ from the G1 viruses characterized above.  
In 2018 we looked at some of the amino acid changes (including Q226L) turning up both lineages over the past 5 or 6 years (see Vet. Sci.: The Multifaceted Zoonotic Risk of H9N2 Avian Influenza).
Whether directly as a standalone pandemic threat, or indirectly as a reassortant partner with another subtype, research continues to suggest that H9N2's threat continues to increase with time.