Sunday, March 18, 2018

Arch. Virology: Co-circulation Of Multiple Genotypes of H7N9 in Eastern China, 2016-2017


While day-to-day reporting on H7N9 (and H5N6) avian flu activity from mainland China has suffered in recent years (at least compared to 2013-14), we continue to get a remarkable flow of quality studies published by Chinese scientists in international journals. 
One of the most remarkable findings we've seen, again and again, is just how much diversity there is in the H7N9 virus. 
Last year a new LPAI Yangtze River Delta lineage became dominant, and a mutated HPAI H7N9 virus emerged in Guangdong Province and began to spread (see MMWR: Increase in Human Infections with Avian Influenza A(H7N9).

H7N9 viruses have also proven themselves to be very promiscuous, reassorting easily with other avian flu viruses, producing numerous new hybrid viruses (genotypes).

Add in a myriad of smaller (although often significant) amino acid changes and the reality is we really don't know how many genetically distinct H7N9 threats there really are in the wild  - we only know that number is large - and getting larger over time.
While most of these variants carry no real evolutionary advantage over the others - and some are likely less biologically fit and doomed to failure - the more variants in circulation, the greater the chances that one will eventually hit the genetic lottery and become a pandemic strain. 
We've a new study (alas, behind a pay wall) published this week in the Archives of Virology that illustrates just how diverse H7N9 has become in Eastern China, with 18 different genotypes identified out of just 41 samples taken in Jiangsu Province.

Equally important, all 41 samples carried the HA G186V and Q226L/I amino acid substitutions, which are linked to switching the virus from binding preferentially to avian (a2,3) receptor cells to mammalian (a2,6) receptor cells.  Some past blogs on these changes include:
PLoS Pathogens: Three Mutations Switch H7N9 To Human-type Receptor Specificity

Sci. Repts: Adaptation of H7N9 in Primary Human Airway Epithelial cells

Eurosurveillance: Genetic Tuning Of Avian H7N9 During Interspecies Transmission
Last year, in Eurosurveillance: Preliminary Epidemiology & Analysis Of Jiangsu's 5th H7N9 Wave, we looked at the study referenced in the opening paragraph of the abstract below. 

Co-circulation of multiple genotypes of influenza A (H7N9) viruses in eastern China, 2016-2017

Xian Qi Email author, Xiaofei An, Yongjun Jiao, Huiyan Yu, Ke Xu, Lunbiao Cui, Shenjiao Wang, Fei Deng, Xiang Huo, Haodi Huang, Qigang Dai, Changjun Bao Email author

First Online: 14 March 2018


Five epidemic waves of human infection with influenza A (H7N9) virus have emerged in China since spring 2013. We previously described the epidemiological characterization of the fifth wave in Jiangsu province.
In this study, 41 H7N9 viruses from patients and live-poultry markets were isolated and sequenced to further elucidate the genetic features of viruses of the fifth wave in Jiangsu province.
Phylogenetic analysis revealed substantial genetic diversity in the internal genes, and 18 genotypes were identified from the 41 H7N9 virus strains. Furthermore, our data revealed that 41 isolates from Jiangsu contained the G186V and Q226L/I mutations in their haemagglutinin (HA) protein, which may increase the ability of these viruses to bind the human receptor. 

Four basic amino acid insertions were not observed in the HA cleavage sites of 167 H7N9 viruses from Jiangsu, which revealed that highly pathogenic avian influenza (HPAI) H7N9 viruses did not spread to Jiangsu province in the fifth wave. 

These findings revealed that multiple genotypes of H7N9 viruses co-circulated in the fifth wave in Jiangsu province, which indicated that the viruses have undergone ongoing evolution with genetic mutation and reassortment. Our study highlights the need to constantly monitor the evolution of H7N9 viruses and reinforce systematic influenza surveillance of humans, birds, and pigs in China.

Despite the surprising lull in H7N9 activity this winter in China, it (or more accurately, `they') remain atop the CDC's Influenza Risk Assessment Tool (IRAT) ranking list of 14 novel flu subtypes/strains that circulate in non-human hosts and are believed to possess some degree of pandemic potential.

No comments: