Tuesday, June 30, 2020

PNAS: Eurasian Avian-like H1N1 Swine Influenza Virus With Pandemic Potential In China



Although avian influenza viruses generally score highest on the pandemic threat scale (see CDC Adds 3 Novel Flu Viruses To IRAT List) - mostly because they tend to produce a greater lethality in humans - swine influenza viruses start out with an important evolutionary advantage; they are already adapted to a mammalian host. 

And as we've discussed often over the past few years (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?), the progression of human influenza pandemics over the past 130 years has been H2, H3, H1, H2, H3, H1, H1 . . . .

Simply put, novel H1, H2, and H3 flu viruses appear to have fewer barriers to overcome in order to jump to humans - and while they may not prove as virulent as H5 & H7 avian subtypes - that puts them at or near the top of our pandemic threats list.

Every summer for the past decade, we've seen anywhere from a handful to several hundred swine-origin influenza cases turning up in humans, primarily connected with state and local agricultural fairs.  Less well documented, we've also gotten reports of swine-origin influenza jumping to humans in Europe and Asia. 

Credit CDC FLuView

Although North American H1, H2, and H3 swine-origin flu viruses are high on our list of pandemic threats, in late 2015 Chen Hualan, director of China's National Avian Influenza Reference Laboratory, was the lead author on a paper that pegged a new, rising swine flu threat in China (see PNAS: The Pandemic Potential Of Eurasian Avian-like H1N1 (EAH1N1) Swine Influenza).

EAH1N1 was a reassortant virus, with elements from H1N1 avian influenza, human H1N1pdm, and swine-origin influenza viruses.  Despite sharing the same subtype designation as a currently circulating seasonal strain, it was genetically different enough to pose a genuine public health threat. 

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.
In an interview, published by Xinhuanet, lead author Chen Hualan stated: 
"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."
Since then, EAH1N1 has become a been a frequent topic of discussion and study. 

Six months later, in Sci Rpts: Transmission & Pathogenicity Of Novel Swine Flu Reassortant Viruses we looked at a study where pigs were experimentally infected with one of these Eurasian-Avian H1N1 swine influenza viruses and the 2009 H1N1pdm virus.

Researchers generated 55 novel reassortant viruses spread across 17 genotypes, demonstrating not only how readily EAH1N1 SIV can reassort with human H1N1pdm in a swine host, but also finding:
`Most of reassortant viruses were more pathogenic and contagious than the parental EA viruses in mice and guinea pigs'. 

Later that same year, in EID Journal: Reassortant EAH1N1 Virus Infection In A Child - Hunan China, 2016, we reviewed the case report on a 30-month old child from Hunan Province, who was infected with one of these reassortant EAH1N1 - H1N1pdm viruses.     

In 2017 we looked at J. Virology: A Single Amino Acid Change Alters Transmissability Of EAH1N1 In Guinea Pigswhile in 2018 we saw Emerg. Microbes & Infect.: Effect Of D701N Substitution In PB2 Of EAH1N1 Swine Flu Viruses which described the growing diversity of novel novel H1N1 and H3N2 flu viruses (including EA H1N1) in China's pig population.

In 2019, we saw a number of studies on EAH1H1, including one that documented the virus in farmed mink in China (see Vet. MicroB.: Eurasian Avian-Like Swine Influenza A (H1N1) Virus from Mink in China).

Since ferrets - which are close relatives of mink - are commonly used in influenza research because their respiratory systems are similar to humans, the ability of this virus to jump to and spread easily in mink is yet another red flag.  

While China holds real-time surveillance information on domestic swine-origin influenza infections close to the vest, a smattering of scientific papers over the past 5 years have increasingly painted EAH1N1 as a potential pandemic threat.   

All of which brings us to a new study, published (alas, behind a paywall) in PNAS, that does little to lower concerns, as they found a greater than 10% seroprevalence for the EAH1N1 among swine workers tested, suggesting that EAH1N1 is gaining human infectivity. 

I'll have more after the break.

Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection

Honglei Sun, Yihong Xiao, View ORCID ProfileJiyu Liu, Dayan Wang, Fangtao Li, Chenxi Wang, Chong Li, Junda Zhu, Jingwei Song, Haoran Sun, View ORCID ProfileZhimin Jiang, Litao Liu, Xin Zhang, Kai Wei, Dongjun Hou, Juan Pu, Yipeng Sun, Qi Tong, Yuhai Bi, Kin-Chow Chang, Sidang Liu, View ORCID ProfileGeorge F. Gao, and Jinhua Liu

PNAS first published June 29, 2020 https://doi.org/10.1073/pnas.1921186117
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Contributed by George F. Gao, April 28, 2020 (sent for review December 9, 2019; reviewed by Ian H. Brown and Xiu-Feng Henry Wan)

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Pigs are considered as important hosts or “mixing vessels” for the generation of pandemic influenza viruses. Systematic surveillance of influenza viruses in pigs is essential for early warning and preparedness for the next potential pandemic. Here, we report on an influenza virus surveillance of pigs from 2011 to 2018 in China, and identify a recently emerged genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus, which bears 2009 pandemic (pdm/09) and triple-reassortant (TR)-derived internal genes and has been predominant in swine populations since 2016.
Similar to pdm/09 virus, G4 viruses bind to human-type receptors, produce much higher progeny virus in human airway epithelial cells, and show efficient infectivity and aerosol transmission in ferrets. Moreover, low antigenic cross-reactivity of human influenza vaccine strains with G4 reassortant EA H1N1 virus indicates that preexisting population immunity does not provide protection against G4 viruses.
Further serological surveillance among occupational exposure population showed that 10.4% (35/338) of swine workers were positive for G4 EA H1N1 virus, especially for participants 18 y to 35 y old, who had 20.5% (9/44) seropositive rates, indicating that the predominant G4 EA H1N1 virus has acquired increased human infectivity. Such infectivity greatly enhances the opportunity for virus adaptation in humans and raises concerns for the possible generation of pandemic viruses.
          (Continue . . . .)

Although we are getting better at identifying potential threats, the two previous pandemics of the last dozen years came out of left field, with absolutely no warning.  Sure, we knew about swine-variant viruses prior to 2009, but no one saw the 2009 H1N1 swine-origin pandemic coming. 

The same can be said for COVID-19.  

We've looked at several bat coronavirus pandemic contenders over the years (see PNAS: SARS-like WIV1-CoV Poised For Human Emergence), but no one strain really stood out, and the SARS-CoV-2 virus that finally did emerge wasn't on that list.

Although EAH1N1 has all of the earmarks of a legitimate pandemic threat, the same was said of H5N1 in 2008 and H7N9 in 2016, and both - at least temporarily - are on the back burner today.  

While it would be great if we could identify the next pandemic threat before it strikes, it is arguably more important to be ready for whatever comes next.  And as COVID-19 has proven, it doesn't necessarily have to be an influenza pandemic. 

As it is, I'm not convinced we are ready to deal with a severe fall wave of COVID-19, much less a new pandemic threat. But ready or not, the next great global health crisis is inevitable, and likely closer in time than we think. 

Whether it originates from EA H1H1 - or comes from totally out of left field -  we need to be a lot better prepared the next time.  

Because as difficult as COVID-19 has been, it is far from being the worst case scenario.