Sunday, October 17, 2021

Pathogens: Emergence and Characterization of a Novel Reassortant Canine Influenza Virus Isolated from Cats

 

#16,252


Although most people believe that the SARS-CoV-2 virus came completely out of left field, long time followers of the science and readers of this blog know that we've been following research into novel coronaviruses in China - and elsewhere - since the the mid-2000s. 

After the SARS scare in 2002-03 (see SARS And Remembrance), and the ongoing outbreaks of MERS-CoV in the Middle East (see Study: A Pandemic Risk Assessment Of MERS-CoV In Saudi Arabia), novel coronaviruses crept up to the number two position on our pandemic watch list; just after novel influenza. 

MERS-CoV wasn't the only CoV of concern, of course. Some of the other coronaviruses with zoonotic potential we've looked at over the years include:

EID Journal: A New Bat-HKU2–like Coronavirus in Swine, China, 2017
Emerg. Microbes & Infect.: Novel Coronaviruses In Least Horseshoe Bats In Southwestern China
PNAS: SARS-like WIV1-CoV Poised For Human Emergence
Study: Hotspots For Bat To Human Disease Transmission
And just 3 months before the Wuhan outbreak, the Johns Hopkins Center For Health Security (JHCHS) - in concert with the World Economic Forum and the Bill & Melinda Gates Foundation - hosted a half-day table top pandemic exercise (#Event201) in New York City which used a fictional CAPS coronavirus as the catalyst for a deadly pandemic scenario. 

We follow what may seem to be obscure - even low probability - zoonotic threats because the next pandemic will most likely arise from some currently little known, emerging virus. 

While high impact H5 or H7 avian influenza viruses - with a track record up to a 50% fatality rate in humans - is the nightmare scenario, all of the human influenza pandemics we know of going back 130 years have been caused by H1, H2, or H3 viruses (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?).

125 Years of Pandemics (Not Including COVID-19) – Credit ECDC 

So it makes sense to pay particular attention to novel versions of these viruses, even though they are unlikely to produce the same level of lethality as a more exotic avian virus (see Everything Old Is Flu Again (Redux)).

Although primarily carried by humans, pigs, birds, horses and marine mammals, over the past 20 years we've also seen H1, H2, and H3  influenza viruses turn up in dogs and cats, both domestic and wild. 
 
Prior to about 2004, both species were believed immune to human flu (see A Dog & Cat Flu Review).
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In 2007 an avian H3N2 virus jumped to dogs in South Korea, and rapidly spread across China.  It arrived in 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:

In 2017, the CDC added Canine H3N2 to their Influenza Risk Assessment Tool (IRAT) list of novel flu viruses with zoonotic potential. 

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).

Starting in the early 2000s, we also became aware that felines were susceptible to some types of avian flu (see HPAI H5: Catch As Cats Can), and in 2011, it was announced that Korea’s canine H3N2 can  jump to cats (see Korea: Interspecies Transmission of Canine H3N2).

While transmission of influenza viruses from humans to companion animals (reverse zoonosis) has been well demonstrated, the ability of cats and dogs to transmit to humans is less well established.  

The best investigated case was an outbreak of avian H7N2 among hundreds of cats across several NYC animal shelters, which found at least two employees infected (see J Infect Dis: Serological Evidence Of H7N2 Infection Among Animal Shelter Workers, NYC 2016) , while 5 others exhibited low positive titers to the virus, indicating possible infection.

Against this backdrop we have a new study, published this past week, on the detection of a novel reassorted  avian-canine-human H3N2 virus in a cat in China.  I've only posted some excerpts from a much longer report, so follow the link to read it in its entirety.  

I'll have postscript when you return.

Emergence and Characterization of a Novel Reassortant Canine Influenza Virus Isolated from Cats

by Jin Zhao 1,*,†,Wanting He 1,†,Meng Lu 1,†,Haijian He 2,* andAlexander Lai 3,*

Published: 14 October 2021

(This article belongs to the Special Issue Epidemiological Study of Infectious Diseases of Animals)


Abstract

Cats are susceptible to a wide range of influenza A viruses (IAV). Furthermore, cats can serve as an intermediate host, and transfer avian influenza virus (AIV) H7N2 to a veterinarian. In this report, a novel reassortant influenza virus, designated A/feline/Jiangsu/HWT/2017 (H3N2), and abbreviated as FIV-HWT-2017, was isolated from nasal swab of a symptomatic cat in Jiangsu province, China.

 Sequence analysis indicated that, whilst the other seven genes were most similar to the avian-origin canine influenza viruses (CIV H3N2) isolated in China, the NS gene was more closely related to the circulating human influenza virus (H3N2) in the region. Therefore, FIV-HWT-2017 is a reassortant virus. 

In addition, some mutations were identified, and they were similar to a distinctive CIV H3N2 clade. Whether these cats were infected with the reassortant virus was unknown, however, this random isolation of a reassortant virus indicated that domestic or stray cats were “mixing vessel” for IAV cannot be ruled out. An enhanced surveillance for novel influenza virus should include pet and stray cats.
(SNIP)

Interspecies transmission of CIV H3N2 to domestic cats in South Korea [4] highlighted a significant public health risk, as pet cats and dogs come into very contact with humans. Both cats and dogs have alpha-2,6 and alpha-2,3 receptors in the trachea and lung, they can serve as intermediate hosts for avian- and mammalian-origin influenza viruses [11,12]. Furthermore, because of their carnivorous behavior, particularly towards birds, cats are at high risk for AIV infection. These infections provide a condition for mammalian adaptation for further interspecies transmission to other mammalian species, including humans. Despite the fact that cats had been shown to be susceptible to CIV H3N2 [13] by experimental transmission, the situation in domestic cats was unknown, particularly in China where the pet cat population has exploded in recent years.

In this report, we characterized a novel reassortant feline influenza H3N2 virus which was randomly isolated from a symptomatic cat. Diagnostic mutations—which were associated with mammalian adaptation—were found. The current COVID-19 pandemic illustrates the importance of the surveillance of novel respiratory viruses in humans, cats and other pet animals. Enhanced surveillance should be instituted to prevent emergence of novel influenza virus or SARS-CoV-2-like viruses to reduce this public health risk.
(SNIP)

Of note, despite the limitation of current report that only one isolate was identified so far, the fact that the human NS gene was included in this reassortant is significant. The NS gene had been shown to play a significant role in the virulence [37,38] by modulating cytokines [39], specifically as an antagonist to alpha-interferon. Whether this novel virus, FIV-HWT-2017, has increased virulence by interfering the host immune response remains to be determined. Furthermore, the number of pet cats in this region significantly increased in the past decades. Moreover, as companion animals, cats have a special status in modern human life. The high frequency of close interactions between cats and dogs presents a high for multiple cross-species virus transmission.

Previous reports had indicated that CIV H3N2 had established as an enzootic infection in dogs from eastern provinces of China. With this host species expanding into cats, considering that China had been known as an “epicenter” for the emergence of novel influenza viruses, enhanced surveillance is warranted. We are currently conducting serological survey to evaluate the extent of CIV H3N2 as well as FIV-HWT infection in dogs and cats from this region. Furthermore, pets had been reported infected with SARS-CoV-2, due to the close and frequent contact with humans, their potential role in influenza virus and SARS-CoV-2 should be further investigated.

(Continue . . . )

Poultry and swine remain most likely reservoir hosts for the next pandemic flu virus, but there is growing evidence that companion animals - particularly dogs and cats - could be intermediate hosts, and potential `mixing vessels' for an emerging novel flu virus.

The CDC currently ranks a Chinese Swine-variant EA H1N1 `G4' as having the highest pandemic potential of any flu virus on their list, but a few favorable (for the virus) mutations could quickly propel a lesser viral threat to the top of the list. 

For more on this topic, you may wish to revisit: