Wednesday, February 14, 2024

Virologica Sinica: The Evolution, Pathogenicity & Transmissibility of Quadruple Reassortant H1N2 Swine Influenza Virus in China

 

#17,909

Over the past decade much attention has been directed to the rising number of swine-origin flu viruses circulating in China. The alarm was initially raised in late 2015 by Chen Hualan, who was the lead author on a paper that identified a new, rising swine flu threat in China:

PNAS: The Pandemic Potential Of Eurasian Avian-like H1N1 (EAH1N1) Swine Influenza).

In 2020, a paper in PNAS: Eurasian Avian-like H1N1 Swine Influenza Virus With Pandemic Potential In China, reported finding a greater than 10% seroprevalence for the EAH1N1 among swine workers tested, suggesting that EA H1N1 was gaining human infectivity.

In February of 2021, the CDC Selected New Swine-Variant EA H1N1 Virus For The Top Of Their IRAT List, giving it the highest emergence score (7.5) of any virus on their list. 

Since then we've seen a number of reports on H1N1, and other subtypes, circulating in Chinese pigs, including:

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

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


Swine are notoriously good mixing vessels for influenza, being susceptible to a wide variety of human, avian, canine, and swine influenza viruses.  Even more exotic avian flu viruses, like H5N1, H9N2, and H10N5, have occasionally been detected in pigs. 


While most of our attention has been directed at EA H1N1 G4 the past few years, today we have a report in Virologica Sinica, on a Quadruple Reassortant H1N2 virus circulating in pigs in China, which already replicates efficiently in human, canine, and swine cells and mice.

Due to its length, I've only posted some excerpts. Follow the link to read it in its entirety.
The evolution, pathogenicity and transmissibility of quadruple reassortant H1N2 swine influenza virus in China: A potential threat to public health

 Xinxin Cui a b c 1, Jinhuan Ma a b c 1, Zifeng Pang a b c 1, Lingzhi Chi d, Cuishan Mai a b c, Hanlin Liu a b c, Ming Liao a b c e, Hailiang Sun a b cShow more
 
https://doi.org/10.1016/j.virs.2024.02.002Get rights and content
 
Highlights
  • Five quadruple reassortant swH1N2 viruses were identified which have close genetic relationship with current human virus.
  • The swH1N2 viruses replicate effectively in human, canine, and swine cells and mice.
  • A/swine/ Shandong/198/2020 replicated efficiently in the respiratory tract of pigs and spread effectively.
  • The swH1N2 viruses pose zoonotic potential, highlighting the need for strengthened surveillance of swH1N2 viruses.
Abstract

Swine are regarded as “intermediate hosts” or “mixing vessels” of influenza viruses, capable of generating strains with pandemic potential. From 2020 to 2021, we conducted surveillance on swine H1N2 influenza (swH1N2) viruses in swine farms located in Guangdong, Yunnan, and Guizhou provinces in southern China, as well as Henan and Shandong provinces in northern China.
We systematically analyzed the evolution and pathogenicity of swH1N2 viruses, and characterized their replication and transmission abilities. The isolated viruses are quadruple reassortant H1N2 viruses containing genes from pdm/09 H1N1 (PB2, PB1, PA and NP genes), triple-reassortant swine (NS gene), Eurasian Avian-like (HA and M genes), and recent human H3N2 (NA gene) lineages.
The NA, PB2, and NP of SW/188/20 and SW/198/20 show high gene similarities to A/Guangdong/Yue Fang277/2017 (H3N2). The HA gene of swH1N2 exhibits a high evolutionary rate. The five swH1N2 viruses tested replicated efficiently in human, canine, and swine cells, as well as in the turbinate, trachea, and lungs of mice.
A/swine/Shandong/198/2020 efficiently replicated in the respiratory tract of pigs and effectively transmitted among them. Collectively, these current swH1N2 viruses possess zoonotic potential, highlighting the need for strengthened surveillance of swH1N2 viruses.

         (SNIP)

In this study, we evaluated pathogenicity of viruses mainly according to their replication and transmission ability in pigs. The pathology of tissues will be considered in the future studies. The G228S mutation in the HA protein facilitates efficient replication and transmission of swine influenza viruses in pigs (Ma et al., 2015). Notably, the SW/198/20 virus possesses the 228S mutation in the HA protein and the 53E mutation in the NP gene, which may explain its ease of replication and transmission in pigs. The potential glycosylation sites of the five swine influenza viruses were analyzed. All strains shared the following five glycosylation sites (28NST30, 40NVT42, 291NCT293, 498NGT500, 557NGS559), while SW/198/20 had an additional glycosylation site at 502NYS504 compared to the other strains. The increase in glycosylation sites may be related to the strain’s heightened pathogenicity (Bourret, 2018, Mon et al., 2020).

5. Conclusions

In this study, we isolated five strains of quadruple reassortant H1N2 viruses from pig herds. These viruses carry the NA gene from the current human H3N2 lineage, and several genes of these H1N2 swine influenza viruses exhibit high sequence similarity to human influenza virus A/Guangdong/Yue Fang277/2017 (H3N2). Moreover, the HA gene of swH1N2 exhibits a rapid evolutionary rate. The virus replicates effectively in mammalian cells and can efficiently replicate in pigs and mice. Additionally, it readily transmits among pigs, indicating its potential for zoonotic and pandemic spread.


For a swine influenza virus to acquire the `right' mutations to become a pandemic virus is probably a much longer-shot than you being dealt a Royal Flush from a randomly shuffled deck of cards (odds: 1 in roughly 650,000).  

It is rare, but due to my misspent youth, I can attest that it can (but seldom does) happen. 

The 2009 H1N1 pandemic virus reportedly spread quietly through North American swine for more than a decade before finally hitting the genetic jackpot, and EA H1N1 G4 has been at it for at least that long, but without success.  

Long shot or not, history shows that pandemic strains emerge often enough (1918, 1957, 1968, 2009) that we take the risk seriously.  

And with the greatly increased diversity of influenza viruses now in circulation, the gaps between pandemics are only expected to become shorter (see BMJ Global: Historical Trends Demonstrate a Pattern of Increasingly Frequent & Severe Zoonotic Spillover Events).