Wednesday, August 17, 2022

PNAS: An EA H1N1-Like Swine Flu Virus With Increased Pathogenicity/Transmissibility Due to Mutations In Its PA

#16,948

We've been following the emergence and evolution of China's EA H1N1 swine flu virus since late 2015, after Chen Hualan et al. published a paper (see PNAS: The Pandemic Potential Of Eurasian Avian-like H1N1 (EAH1N1) Swine Influenza) describing its prevalence, genetics, and transmissibility (in ferrets)

In the `Significance' section the authors boiled it down to this:
Here, we found that, after long-term evolution in pigs, the EAH1N1 SIVs have obtained the traits to cause a human influenza pandemic.
Hualan - director of China's National Avian Influenza Reference Laboratory - gave an interview to the Chinese News Agency Xinhua where she pegged the EA (Eurasian Avian-like) H1N1 swine virus (EAH1N1) as having perhaps the greatest pandemic potential of any of the novel viruses in circulation.
Avian-like H1N1 swine flu may "pose highest pandemic threat": study

WASHINGTON, Dec. 28 (Xinhua) -- The Eurasian avian-like H1N1 (EAH1N1) swine flu viruses, which have circulated in pigs since 1979, have obtained the ability to infect humans and may "pose the highest pandemic threat" among the flu viruses currently circulating in animals, Chinese researchers said Monday.
(Snip)

"Based on scientific analysis and comprehensive comparison of the main animal flu viruses: H1N1, H3N2, H5N1, H7N9, H9N2 and EAH1N1, we found the EAH1N1 is the one most likely to cause next human flu pandemic. We should attach great importance to the EAH1N1."

(Continue . . . )

Since then we've followed work on this emerging virus, including:

Sci Rpts: Transmission & Pathogenicity Of Novel Swine Flu Reassortant Viruses

EID Journal: Reassortant EAH1N1 Virus Infection In A Child - Hunan China, 2016

J. Virology: A Single Amino Acid Change Alters Transmissability Of EAH1N1 In Guinea Pigs

Emerg. Microbes & Infect.: Effect Of D701N Substitution In PB2 Of EAH1N1 Swine Flu Viruses

Two years ago, researchers writing in PNAS: Eurasian Avian-like H1N1 Swine Influenza Virus With Pandemic Potential In China, reported > 10% seroprevalence for the EAH1N1 among swine workers tested, suggesting that EAH1N1 was gaining in its ability to jump species.

This report led to a flurry of `risk assessments' by public health agencies on EA H1N1 `G4', including:




In early 2021 the CDC ranked a Chinese Swine-variant EA H1N1 `G4' as having the highest pandemic potential of any flu virus on their list, and since then we've seen additional studies that have only exacerbated concerns. 

EID Journal: Zoonotic Threat of G4 Genotype Eurasian Avian-Like Swine Influenza A(H1N1) Viruses, China, 2020

EID Journal: Natural Reassortment of EA H1N1 and Avian H9N2 Influenza Viruses in Pigs, China

EID Journal: Potential Threats to Human Health from EA H1N1 Viruses and Reassortants

The point being, EA H1N1 has garnered a great deal of attention over the past 7 years, and for very good reasons.  While none of this guarantees that EA H1N1 will spark the next pandemic, it is certainly a plausible contender. 

All of which brings us to a new study - published yesterday in PNAS, by Yoshihiro Kawaoka and Hualan Chen et al.- that examines the increased pathogenicity and transmissibility of an EA H1N1 reassortant virus isolated in Liaoning province in Northeastern China.

While there is no huge bombshell in this report, it adds incrementally to our understanding of the continued evolution of EA H1N1 in China, and finds similarities to the evolution of the 2009 H1N1 pandemic virus

The full report is behind a paywall, but we have the link, abstract, and a significance statement that provide us with reasonably good detail.  I'll have a brief postscript after the break. 

A Eurasian avian-like H1N1 swine influenza reassortant virus became pathogenic and highly transmissible due to mutations in its PA gene

 Fei Meng, Huanliang Yang, Zhiyuan Qu, +7 , Yan Chen, Yijie Zhang, Yaping Zhang, Liling Liu, Xianying Zeng, Chengjun Li, Yoshihiro Kawaoka and Hualan Chen 

August 15, 2022
119 (34) e2203919119

Abstract

Previous studies have shown that the Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses circulated widely in pigs around the world and formed multiple genotypes by acquiring non-hemagglutinin and neuraminidase segments derived from other swine influenza viruses. Swine influenza control is not a priority for the pig industry in many countries, and it is worrisome that some strains may become more pathogenic and/or transmissible during their circulation in nature. 

Our routine surveillance indicated that the EA H1N1 viruses obtained different internal genes from different swine influenza viruses and formed various new genotypes. In this study, we found that a naturally isolated swine influenza reassortant, A/swine/Liaoning/265/2017 (LN265), a representative strain of one of the predominant genotypes in recent years, is lethal in mice and transmissible in ferrets.

LN265 contains the hemagglutinin, neuraminidase, and matrix of the EA H1N1 virus; the basic polymerase 2, basic polymerase 1, acidic polymerase (PA), and nucleoprotein of the 2009 H1N1 pandemic virus; and the nonstructural protein of the North American triple-reassortment H1N2 virus

By generating and testing a series of reassortants and mutants, we found that four gradually accumulated mutations in PA are responsible for the increased pathogenicity and transmissibility of LN265. We further revealed that these mutations increase the messenger RNA transcription of viral proteins by enhancing the endonuclease cleavage activity and viral RNA–binding ability of the PA protein. Our study demonstrates that EA H1N1 swine influenza virus became pathogenic and transmissible in ferrets by acquiring key mutations in PA and provides important insights for monitoring field strains with pandemic potential.

          (Continue . . . )

While EA H1N1 has been on our radar now for 7 years without generating a pandemic strain, we may have caught a bit of a break in 2018 when African Swine Fever (ASF) arrived and quickly spread in China leading to the loss (through infection, or culling) of roughly half of China's swine population. 

Fewer pigs, and curbs on transportation of swine, likely slowed - and may have even disrupted - the evolution of EA H1N1.  

China's swine industry is reportedly recovering, and while that may be good news for farmers and a protein hungry nation, it may provide the EA H1N1 virus with new opportunities to reassort into a genuine public health threat. 

Nothing happens in a vacuum, of course, and evolution is rarely steady or linear. There are too many factors at play that could either enhance, or derail, EA H1N1's chances of hitting the pandemic jackpot. 

All of which makes trying to predict the source of the next pandemic a mug's game. But nature has a deep bench, and unlimited time, making another pandemic inevitable.