Dogs as `mixing vessels' for influenza
#17,087
While influenza A viruses are believed to have originated in avian species (primarily waterfowl), over time they’ve managed to infect, and adapt to, a wide variety of non-avian hosts.
Humans, obviously, and swine . . . but we’ve also seen influenza A viruses documented in mink, bats, elephant seals, small peridomestic mammals, and companion animals like cats and dogs.
For the most part, these flu viruses have adapted to, and circulate within, a limited host-range. Only rarely do we see a swine-origin virus infect humans, or the spillover of an avian virus into a mammalian host.
But these viruses are constantly evolving - often reassorting with other influenza A viruses - and given enough opportunities, can occasionally produce a new, and highly transmissible, novel virus with pandemic potential.
So we watch these spillovers closely.
While not as susceptible as pigs, or mink, companion animals are of particular concern because they are well placed to bridge the gap between contact with wildlife and close contact with humans (see CDC: A Reminder About Pets and Avian Flu).
In 2016, we saw an outbreak of avian H7N2 sweep through hundreds of cats across several NYC animal shelters, eventually infecting several employees.
Dogs are particularly susceptible to two forms of canine influenza (H3N8 and H3N2), and while these canine strains have never been known to infect humans, they are close cousins to pandemic (and seasonal) strains of influenza that do.
Since it emerged in 2006, we've seen Canine H3N2 jump to other species (see Korea: Interspecies Transmission of Canine H3N2), as well as reassorting with other avian and human flu viruses, Including:A Canine H3N2 Virus With PA Gene From Avian H9N2 - Korea
Canine H3N2 Reassortant With pH1N1 Matrix Gene
Virology J: Human-like H3N2 Influenza Viruses In Dogs - Guangxi, China
Interspecies Transmission Of Canine H3N2 In The Laboratory
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.(SNIP)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
Today we've another study, published earlier this month in the Virology Journal, that also documents the infection and onward transmission of canine H3N2 in non-canine hosts (guinea pigs). This is a lengthy and detailed open-access report, and I've only posted some excerpts.
Follow the link to read it in its entirety. I'll have a postscript when you return.
Ratanaporn Tangwangvivat, Supassama Chaiyawong, Nutthawan Nonthabenjawan, Kamonpan Charoenkul, Taveesak Janethanakit, Kitikhun Udom, Sawang Kesdangsakonwut, Rachod Tantilertcharoen, Aunyaratana Thontiravong & Alongkorn Amonsin
Virology Journal volume 19, Article number: 162 (2022) Cite this article
Abstract
Background
Influenza A virus causes respiratory disease in many animal species as well as in humans. Due to the high human-animal interface, the monitoring of canine influenza in dogs and the study of the transmission and pathogenicity of canine influenza in animals are important.
Methods
Eight-week-old beagle dogs (Canis lupus familaris) (n = 13) were used for the intraspecies transmission model. The dogs were inoculated intranasally with 1 ml of 106 EID50 per ml of canine H3N2 influenza virus (A/canine/Thailand/CU-DC5299/2012) (CIV-H3N2). In addition, 4-week-old guinea pigs (Cavia porcellus) (n = 20) were used for the interspecies transmission model. The guinea pigs were inoculated intranasally with 300 µl of 106 EID50 per ml of CIV-H3N2.
Results
For the Thai CIV-H3N2 challenged in the dog model, the incoculated and direct contact dogs developed respiratory signs at 2 dpi. The dogs shed the virus in the respiratory tract at 1 dpi and developed an H3-specific antibody against the virus at 10 dpi. Lung congestion and histopathological changes in the lung were observed. For the Thai CIV-H3N2 challenge in the guinea pig model, the incoculated, direct contact and aerosol-exposed guinea pigs developed fever at 1–2 dpi. The guinea pigs shed virus in the respiratory tract at 2 dpi and developed an H3-specific antibody against the virus at 7 dpi. Mild histopathological changes in the lung were observed.
Conclusion
The result of this study demonstrated evidence of intraspecies and interspecies transmission of CIV-H3N2 in a mammalian model.
Our result raises the possibility of the transmission of canine influenza from dogs or intermediate mammals (guinea pigs) to humans, since both SAα 2,3-gal and SAα 2,6-gal receptors are also present in the human respiratory tract. A previous study on sialic acid receptor binding showed that the mutation of HA (Q226L, Q226R, and G228S) increases the binding preference and binding affinity of H3N2 influenza viruses for human-type receptors ([29]. Thai CIV-H3N2 dose not contain HA mutations at Q226 or G228, indicating a possible lower binding affinity of the virus for the mammalian receptor. Unfortunately, we did not perform sialic acid receptor binding analysis on Thai CIV-H3N2 to confirm its binding affinity.To date, there are no reports of CIV-H3N2 infection in humans; however, the reassortment of the viruses to novel or more virulent forms should not be ignored. The reassortment of CIV-H3N2 was reported in a previous study [30]. The reassortment of contemporary influenza viruses can result in higher viral replication transmissibility and virulence [31, 32]. Moreover, dog breed can also contribute to a more human-animal interface and lead to viral spillover [33].
Conclusion
In this study, the intraspecies transmission of Thai CIV-H3N2 was demonstrated in experimentally challenged dogs. The infected dogs in the inoculated and direct contact groups presented clinical signs, such as fever, serous nasal discharge, ocular discharge, coughing, depression and loss of appetite. All dogs could shed the virus and had an antibody response against CIV-H3N2. The interspecies transmission of CIV-H3N2 was demonstrated in experimentally challenged guinea pigs. The infected guinea pigs showed fever and mild clinical signs related to respiratory disease. Guinea pigs can shed the virus and develop H3-specific antibodies.
In Thailand, there are no recommendations for canine influenza vaccines used in pet animals. The canine influenza vaccine for dogs has been developed and used in Korea and China. The inactivated A/canine/Korea/01/07 (H3N2) was shown to be highly efficient in reducing fever and lung lesions and decreasing viral shedding in dogs [34]. In addition, the live-attenuated vaccine was developed and showed higher immunogenicity and protective efficacy than the inactivated influenza vaccine [35]. Canine influenza vaccination in dogs will be another option for the prevention and control of canine influenza virus among dogs and minimize transmission. Moreover, the personal hygiene of pet owners and animal health care workers should be regularly practiced to avoid close contact transmission. One health approach can help raise awareness of the human-domestic animal interface contributing to the potential zoonotic transmission of influenza.
While currently quantified as a relatively low-risk virus, in 2017 the CDC added Canine H3N2 to their IRAT (Influenza Risk Assessment Tool) listing of novel flu subtypes/strains that circulate in non-human hosts and are believed to possess some degree of pandemic potential. Their evaluation reads:
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).A reminder that nature's laboratory is open 24/7, and is constantly looking to create a `better' virus.
