Monday, October 10, 2022

Preprint: Increased Public Health Threat of Avian-origin H3N2 Influenza Virus During Evolution in Dogs

Dogs as `mixing vessels' for influenza

#17,054

In 2007 an avian H3N2 virus jumped to dogs in South Korea, and rapidly spread across China. Analysis showed that the HA and NA genes of the A/canine/Korea/01/2007 (H3N2) isolate were closely related to those identified in 2003 from chickens and doves in South Korea.   

Only three years earlier, equine H3N8 jumped from horses to dogs at a racetrack in Florida (see EID Journal article Influenza A Virus (H3N8) in Dogs with Respiratory Disease, Florida) and began spreading widely. 

Canine H3N2 arrived to the United States in 2015 (see CDC Statement On H3N2 Canine Influenza In Chicago Region) and has since spread nationally. Some early blogs on the evolution of Canine H3N2 virus include:

H3N2: [A/canine/Illinois/12191/2015]

The H3N2 canine influenza virus is an avian flu virus that adapted to infect dogs. This virus is different from human seasonal H3N2 viruses. Canine influenza A H3N2 virus was first detected in dogs in South Korea in 2007 and has since been reported in China and Thailand. It was first detected in dogs in the United States in April 2015. H3N2 canine influenza has reportedly infected some cats as well as dogs. There have been no reports of human cases.

Summary:  The average summary risk score for the virus to achieve sustained human-to-human transmission was low risk (less than 4). The average summary risk score for the virus to significantly impact public health if it were to achieve sustained human-to-human transmission was in the low risk range (less than 4).

Since then, dogs and cats have increasingly been viewed as potential hosts and `mixing vessels' for novel flu viruses.  A few (of many) past blogs include:

China: Avian-Origin Canine H3N2 Prevalence In Farmed Dogs

J. Virology: Zoonotic Risk, Pathogenesis, and Transmission of Canine H3N2

Access Microbiology: Inter-Species Transmission of Avian Influenza Virus to Dogs

Both of these canine flu viruses have continued to evolve, spread, and reassort with other viruses, raising concerns that dogs could serve as a `mixing vessel' for influenza (see Study: Dogs As Potential `Mixing Vessels’ For Influenza), much in the way that pigs are viewed today.

As companion animals dogs (and cats) are uniquely positioned to serve as a conduit for novel flu viruses to jump to humans.  In late 2016 when we saw an avian H7N2 virus sweep through hundreds of cats housed at multiple New York Animal shelters - which also infected at least two people. 

All of which brings us to a new preprint, published today on the bioRxiv website, from Chinese scientists who warn on the continued evolution of canine H3N2, which appears to be moving towards becoming a more `humanized' virus. 

This is a long (57-pagea) and detailed report, so I've just posted the abstract and some excerpts from the discussion. Follow the link to download and read the full article. 

Increased public health threat of avian-origin H3N2 influenza virus during evolution in dogs
Mingyue Chen, Yanli Lyu, Fan Wu, Ying Zhang, Hongkui Li, Rui Wang, Yang Liu, Xinyu Yang, Liwei Zhou, Ming Zhang, Qi Tong, Honglei Sun, Juan Pu, Jinhua Liu, Yipeng Sun

doi: https://doi.org/10.1101/2022.10.10.511550 Preview PDF

Abstract

Influenza A viruses in animal reservoirs repeatedly cross species barrier to infect humans. Once an animal-borne virus with novel antigenicity acquired the efficient human to human transmissibility, it will become epidemic in the population. 

Dogs are the closest animal companions to humans and canine respiratory tract expresses both SAα2,3-(avian type) and α2,6-Gal (human type) receptors. However, the role of dogs in the ecology of influenza viruses is unclear. H3N2 avian influenza viruses transmitted to dogs around 2006 and have formed stable lineages. The long-term epidemic of avian-origin H3N2 virus in canine offers the best models to investigate the effect of dogs on the evolution of influenza viruses. 

Here, we carried out a systematic and comparative identification of the biological characteristics of H3N2 canine influenza viruses (CIVs) isolated in the worldwide over 10 years.
We found that during the adaptation of H3N2 CIVs to dogs, H3N2 CIVs became to recognize the human-like SAα2,6-Gal receptor, gradually increased HA acid stability and replication ability in human airway epithelial cells, and acquired a 100% transmission rate via respiratory droplet in ferret model, which were essential hallmarks of being adapted to humans.

We also identified that the frequency of substitutions related to human adaptation has gradually increased in H3N2 CIVs, and determined four cumulative molecular changes responsible for the increased airborne transmission ability in ferrets.
Our results suggested that canine may serve as an intermediate for the adaptation of avian influenza virus to human. Continuous surveillance coordinated with risk assessment for CIVs is necessary
Discussion 
By evaluating the biological characteristics of avian-origin H3N2 CIVs isolated in dogs from different years, we found that the effective infection and transmission in  dogs was not an intrinsic property possessed by H3N2 CIVs but through stepwise adaptation. Of note, threats to human health increased during H3N2 CIVs adaptation to dogs. 

Specifically, we observed changes in receptor binding specificity from recognizing only α-2,3-linked sialosides to recognizing both α-2,3- and α-2,6-linked sialosides and gradually increased HA acid stability and replication in human airway epithelial cells and ferrets, and can transmit by aerosol among ferrets. 

In addition,  humans lack immunity to the H3N2 CIVs, and increased isolation of H3N2 CIVs in the dog population increased the chance of transmission to humans. Therefore, we suggested that dogs was a potential intermediate host of avian influenza viruses to  adapt to humans. 

(SNIP)

Taken together, our results suggests that after the avian-origin H3N2 influenza viruses were introduced to dogs, they adapted to canines and increased the threat to public health. Controlling the prevailing H3N2 CIVs in dogs and continuous  monitoring their biological characteristics should be implemented.

         (Continue . . . )


While this report focuses on the canine-avian H3N2 virus, earlier this year we saw the first two (known) infections with avian H3N8 (see China: NHC Confirms Human Avian H3N8 Infection In Henan Province).  

In the first of these infections (a 4 year-old boy) the family dog and cat both tested positive for H3N8, and a full-length HA sequencing revealed the HA to be identical to the boy's.  While it isn't clear who infected who, this does speak to the growing host range of avian-H3N8.  

A not-so-subtle reminder that Nature's laboratory is open 24/7, and it never stops trying to create a better virus. 

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