Pathogenicity and Transmissibility of Bovine-derived HPAI H5N1 B3.13 Virus in Pigs

 

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Just shy of a year ago (March 21st, 2024) we learned of the first report of HPAI H5N1 in infected goat kids in Minnesota - which was followed 4 days later by the first USDA Statement on HPAI In Dairy Cattle in Texas & Kansas Herds.  

Although not entirely unheard of (see A Brief History Of Influenza A In Cattle/Ruminants), this was quite unexpected, and within 60 days infected cattle had been detected in 9 states.  

In May of last year the USDA also announced that HPAI H5N1 had been Detected In Alpacas the previous March.  This sudden expansion of the host range of H5N1 was largely attributed to the emergence of a B3.13 genotype, and immediately concerns were raised over its potential for being introduced into swine.

While only rarely reported, we've seen H5 spillovers into swine before:

WHO H5N1 detected in pigs in China (2004)

EID Journal: Asymptomatic H5N1 In Pigs (2010)

An Unusual Report Of H5N1 in Pigs (Indonesia 2016)

Sci. Rpts.: Evidence Of H5N1 Exposure In Domestic Pigs - Nigeria (2018)

Seroconversion of a Swine Herd in a Free-Range Rural Multi-Species Farm against HPAI H5N1 2.3.4.4b Clade Virus (2023)

Past attempts to infect pigs experimentally have suggested pigs may not be an ideal host for H5N1 (see 2023's EID Journal: Low Susceptibility of Pigs against Experimental Infection with HPAI Virus H5N1 Clade 2.3.4.4b), although the evolutionary trajectory of HPAI H5 the past few years has been towards greater mammalian adaptation.

Just prior to the emergence of B3.13 in U.S. dairy cattle, the H5N1 variant of greatest concern was a mutated virus found spreading efficiently in farmed mink in Spain in November of 2022 (see CDC: New IRAT Risk Assessment On Mink Variant of Avian H5N1).

In May of last year, in Emerg. Inf. & Microbes: Pigs are Highly Susceptible To But Do Not Transmit Mink-Derived HPAI H5N1 Clade 2.3.4.4b, a study reassuringly reported that this mink-derived variant did not transmit between pigs. 

While the amount of testing of swine isn't at all clear, last fall H5N1 was detected in two pigs on a farm in Oregon - although not from the bovine B3.13 genotype - but rather from a D1.2 genotype reported in poultry.  Both pigs were euthanized, and no further spread was detected. 

Until a month ago, only the B3.13 genotype had been detected in dairy cows.  

That exclusivity vanished in early February with the announcement that the D1.1 genotype had been detected in Nevada  - and later in Arizona - dairy herds (see USDA Summary Of Nevada's H5N1 Genotype D1.1 Spillover Into Cattle).  

Today we have a preprint which describes the experimental infection of pigs with the bovine B3.13 genotype of the virus, and once again it finds that while pigs are moderately susceptible to infection, they aren't yet able to transmit the virus efficiently to other pigs. 

The full preprint runs 26 pages, and many will want to read it in its entirety.  I've only posted some excerpts, so follow the link.  I'll return with a postscript after the break. 

Pathogenicity and transmissibility of bovine-derived HPAI H5N1 B3.13 virus in pigs

Taeyong Kwon, Jessie D Trujillo, Mariano Carossino, Heather Machkovech, Konner Cool, Eulim Lyoo, Gagandeep Singh, Sujan Kafle, Shanmugasundaram Elango, Govindsamy Vediyappan, Wanting Wei, Nicholas R. Minor, Franco Matias Ferreyra, Igor Morozov, Natasha N Gaudreault, Udeni Balasuriya, Lisa Hensley, Diego Diel, Wenjun Ma, Thomas Friedrich, Juergen A Richt

doi: https://doi.org/10.1101/2025.03.04.641414

This article is a preprint and has not been certified by peer review [what does this mean?].

Preview PDF

Abstract

Since the first emergence of highly pathogenic avian influenza (HPAI) H5N1 viruses in dairy cattle, the virus has continued to spread, reaching at least 16 states and at least 950 dairy herds in the United States. Subsequently, spillovers of the virus from dairy cattle to humans have been reported. Pigs are an important reservoir in influenza ecology because they serve as a mixing vessel in which novel reassortant viruses with pandemic potential can be generated.

Here, we show that oro-respiratory infection of pigs resulted in productive replication of a bovine-derived HPAI H5N1 B3.13 virus. Infectious viruses were mainly identified in the lower respiratory tract of principal infected pigs, and sero-conversion was observed in most of the principal pigs at later time points.

In one animal, we detected the emergence of a mutation in hemagglutinin (HA) previously associated with increased affinity for mammalian-type alpha 2,6-linked sialic acid receptors, but this mutation did not reach consensus levels. Sentinel contact pigs remained sero-negative throughout the study, indicating lack of transmission.

The results support that pigs are susceptible to a bovine-derived HPAI H5N1 B3.13 virus, but this virus did not replicate as robustly in pigs as mink-derived HPAI H5N1 and swine-adapted influenza viruses.

         (SNIP)

In summary, our data suggests that pigs are moderately susceptible to the bovine-derived HPAI H5N1 B3.13 virus but do not transmit to sentinel pigs. Given the important role of pigs in IAV ecology as a mixing vessel for generating the novel reassortant viruses with pandemic potential, enhanced surveillance of pigs is warranted.

         (Continue . . . )

Although the news regarding swine and H5N1 continues to be reassuring, the virus continues to evolve at a furious rate, and what we can say about genotype B3.13 or the mink-derived variant from Spain, may not apply to D1.1, D1.2, or any future variants that may emerge. 

Eleven months ago, in ECDC/EFSA Report: Drivers For a Pandemic Due to Avian Influenza, the authors cautioned that we cannot afford to be complacent:

• The available scientific information suggests that the current 2.3.4.4b H5 strains are poorly adapted to pigs. However, field and experimental evidence indicates that infection in this species is possible and generally of a subclinical nature. Active surveillance should be routinely implemented in pigs exposed to or in proximity of either HPAI infected poultry or wild birds or other mammals, given the important role played by this species in the emergence of reassortant zoonotic viruses. 
• Considering the plethora of new H5N1 genotypes which have emerged in the last 3 years and the ability of these viruses to acquire mutations that confer an increased adaptation to mammals, a periodic reassessment of the permissiveness of pigs to emerging HPAI H5N1 viruses is needed.

A year ago today, this is pretty much what the scientific consensus on the risk of H5N1 in cattle would have looked like; Infection is possible, but spread is unlikely. 

A reminder of how quickly things can change. 

PAHO: Epidemiological Update Avian Influenza A(H5N1) in the Americas Region (Mar 4th)

 Credit PAHO H5N1 Interactive Dashboard

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It's been a little over a month since the last PAHO Epidemiological Update on Avian Influenza, with the newest released yesterday.  The report summary states:

Epidemiological Update - Avian Influenza A(H5N1) in the Americas Region - 4 March 2025


Download

Since 2022 and as of epidemiological week (EW) 8 of 2025, a total of 19 countries and territories in the Americas Region reported 4,713 animal outbreaks of avian influenza A(H5N1) to the World Organization for Animal Health (WOAH), representing 325 additional outbreaks, since the last epidemiological update published by the Pan American Health Organization/World Health Organization (PAHO/WHO) on 24 January 2025.

A total of 74 human infections caused by avian influenza A(H5) have been reported in four countries in the Americas between 2022 and 25 February 2025, with three additional cases reported since the last epidemiological update published by PAHO/WHO.

The full 11-page report is worth reading, and once again PAHO stresses:

PAHO/WHO urges Member States to work collaboratively and intersectorally to preserve animal health and protect public health. It is essential that preventive measures for avian influenza be implemented at the source, protocols for detection, notification and rapid response to outbreaks in animals be established, surveillance for both animal and human influenza be strengthened, epidemiological and virological investigations be carried out in relation to animal outbreaks and human infections, genetic information about viruses be shared, thereby fostering collaboration between animal and human health settings, effectively communicating risk , and ensuring preparedness for a potential influenza pandemic at all levels (20, 21).

Reports like this are valuable, but rarely do they convey the full impact of an outbreak. While there are 35 PAHO member nations (plus 4 associate members), less than half have reported H5 (in any host) since 2022.  And as the following graphic indicates, very few reports have been submitted from Central and South American countries over the last 30 days.

While this may be reflective of a genuine lull in outbreaks, it may also be a byproduct of `suboptimal' surveillance and reporting.  Even here in the United States, reporting of H5N1 infections - particularly in mammals - has been slow in coming.

While governments love to release reassuringly low `official' numbers, the surveillance and reporting of infectious diseases has never been particularly accurate, or all encompassing.  As the following CDC graphic illustrates, official numbers often only include the very tip of the pyramid. 

Sometimes this is due to mild, or non-remarkable, presentation in the population. Illnesses that mimic viral respiratory infections, are notoriously easy to miss.  Other times, there are simply gaps in surveillance and reporting (either intentional or due to a lack of resources). 

We can see this demonstrated by the following graphic showing that in the latest CDC COVID Nowcast, only 1 HHS region collected and submitted enough (n=300) sequences to warrant inclusion in the current numbers.   

Over the past couple of years, 90% of the world's nations have stopped reporting COVID fatalities or hospitalizations to the WHO (see The Wrong Pandemic Lessons Learned).  While COVID is no longer the scourge it once was, for political and economic reasons, we've artificially deflated the numbers in order to speed its departure. 

A policy that will pay dividends up until the time a new and more virulent COVID variant emerges, and catches us with our surveillance down.  But I digress . . . 

The CDC's official case count of H5N1 infections in the United States over the past year (see below) stands at 70, but it doesn't tell the full story.  Not included are 7 locally confirmed `probable' cases, and a growing number of serologically positive cases (see here, here, and here) which are not officially counted. 

Add in the anecdotal reports of symptomatic farm workers who refused testing (see EID Journal: Avian Influenza A(H5N1) Virus among Dairy Cattle, Texas, USA), and the `official' number of 70 human cases becomes even less representative of reality. 

In nearly every risk analysis the authors provide a `confidence level' in the data; usually High, Moderate, or Low.

Increasingly, my confidence in the reporting - even from countries (including my own) which have historically been more `open' to releasing information - has dwindled. Although it is arguably getting worse, it has devolved steadily over the past several years (see 2022's Flying Blind In The Viral Storm).

While I would love to point to the lower number of dairy herds recently reported as infected by H5N1, or the recent slowdown in human infections in the United States (and the world), as proof that the H5Nx threat is declining, the quality of the data is unknown. 

I'm sure there are genuine short-term economic or political gains to be had by downplaying or under-reporting HPAI H5, COVID, and other emerging diseases. 

And maybe we get very lucky, and H5 really does fade away.

But like with Russian Roulette, this is a game that can only be played for so long before it ends badly.

USDA Adds 7 More Domestic Cats To H5N1 List

 

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While undoubtedly underreported, the toll that H5N1 is taking on domestic cats - which the USDA only began tracking 9 months ago - continues to rise.  Last week, 10 cats were added,  and today 7 more are added to the list (106 out of 521 reports).

Among them is a single cat from New Jersey, even though last week's report from the NJ DOH indicated at least two cats had tested positive, and others on the property were ill.  This week four states reported cases in domestic cats (Washington, New Jersey, Oregon & Colorado)

 

At the same time, we are seeing very few other animals reported (by the states), even though there appears to be a lot of virus in the environment.  Many states have yet to report any wildlife infections (see map above), while many others have only reported 1 or 2.  

Admittedly, many infected animals either recover - or die unnoticed in the wild - particularly in less accessible areas like the Everglades of Florida, the bayous of Louisiana, or desert and mountainous regions out west.

But it does seem as if some states are far more diligent in seeking out, testing, and reporting cases than others.  Since the evolution of H5N1 can occur in many different hosts, our `don't test, don't tell' attitude - which also extends to livestock - leaves us wide open to nasty surprises. 

Since the emergence of a new, more mammalian-adapted H5N1 virus in 2021, we've seen a number of outbreaks in cats around the world (see reports from Poland & South Korea). In those outbreaks, as well as several recent cases in California and Oregon, the consumption of raw meat and/or milk was the likely exposure.

In other cases cat have been believed infected through predation of wild birds or rodents, or via exposure to contaminated areas outside of the home (see California: San Mateo County Warns Residents After Stray Cat Found With H5N1).

While the USDA lists 106 domestic cats infected with H5N1 (and > 5 dozen wild or captive large cats), no one knows the real number. Feral cats are unlikely to be tested for the virus, and we've seen reports of household pets that died, but were never tested.

Although we haven't seen it happen with HPAI H5, cats have been shown capable of transmitting  avian flu (H7N2) to humans (see J Infect Dis: Serological Evidence Of H7N2 Infection Among Animal Shelter Workers, NYC 2016),  raising concerns over their potential role in spreading the H5 virus, or affecting its evolution. 

For now, the CDC continues to rank the risk to general public from avian flu as low.

But they do provide very specific guidance to pet owners on how to limit their risk of infection from the virus (see What Causes Bird Flu in Pets and Other Animals).  And given the amount of virus in the environment right now, it is advice very much worth heeding. 

WHO: Update & Risk Assessment On Cluster of Community Deaths in Basankusu, Equateur, DRC

  

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Last week WHO AFRO published a report on a DRC Investigation on Cluster of Illness and Community Deaths in Equateur Province, and while the cause remained undetermined, tests for Ebola and Marburg had come back negative. 

As we've seen often over the years, most `mystery' outbreaks turn out to be due to something already known (malnutrition, measles, malaria, meningitis, contaminated food or water, etc.), but every once in a while something more exotic is at work.  

Late yesterday the WHO published the following update, which describes the outbreak as both `localized'  and `declining' - and while the cause has yet to be determined - has set the local public health risk at `moderate', and the national and global risk as `low'.

Due to its length, I've only posted some excerpts.  Follow the link to read the full report. 

Cluster of community deaths in Basankusu, Equateur- Democratic Republic of the Congo
3 March 2025

Situation at a glance

On 9 February 2025, officials in the Democratic Republic of the Congo reported to regional health authorities a cluster of 24 unexplained community deaths in a single village in Ekoto health area, Basankusu health zone, Equateur province. As of 25 February, a total of 53 deaths have been reported, with the last death occurring on 22 February. Deaths have occurred in all age groups, but adolescents and young adults, particularly males, appeared to be disproportionately affected in the initial cluster reported. Disease progression appeared to be fast, with a median time from onset of symptoms to death of one day.

 Given the rapid decline in the incidence of reported deaths, their geographic clustering, the age profile of deaths and the rapid disease progression in the initial cluster, working hypotheses include chemical poisoning or a rapid onset bacterial meningitis cluster, on a background of malaria and other infectious illnesses endemic in the region. The definitive cause of illness remains undetermined, with initial samples testing negative for Ebola and Marburg viruses. Field investigations and additional laboratory testing are ongoing including but not limited to the cerebrospinal fluid testing and the toxicological analysis of environmental samples, including water and other samples to explore chemical causes. Local authorities began surveillance with a broad case definition including any individual with fever and at least one other symptom, to better understand disease patterns. 

A total of 1318 patients had symptoms meeting the working suspected case definition as of 25 February 2025. Approximately 50% of malaria tests performed on these cases tested positive for malaria, the cases identified through this enhanced surveillance therefore likely reflect the various febrile illnesses in the area. With the available information, WHO assesses the local public health risk as moderate, and the national and global public health risk as low.

          (SNIP) 

          (SNIP)

WHO risk assessment

Since the initial cluster of deaths was reported on 9 February 2025, there has been an overall downward trend in deaths. The most recent death was reported on 22 February 2025. Current epidemiological information suggests a localized event with a steady decline in incidence, not expanding in time and place. Given the clinical presentation of deaths and the speed from symptom onset to death in this unusual cluster, current differentials include a rapid onset bacterial meningitis cluster or a contamination by a chemical poisoning as key hypotheses in a context of high incidence of other common infectious diseases in the areas, particularly malaria.

Operational challenges related to this event involve the isolation of Basankusu and resulting logistical barriers, as it is located in a forested region, approximately 450 kilometers from the nearest major city of Mbandaka and has poor infrastructure. The remoteness of Basankusu has hindered the timeliness of the initial investigation and response activities and poses challenges to laboratory testing. Samples must be collected, stored, and shipped long distances to a larger city with laboratory testing capacity (either Mbandaka or Kinshasa), introducing delays in diagnosis. Access to care is another key challenge, as the region lacks robust healthcare services, and the region’s poor infrastructure makes travel to neighboring health zones difficult, leading to delays in treatment.

The province faces a severe urban water crisis with only 5% of its urban population having access to drinking water. The water network suffers frequent leaks and has never been rehabilitated. Many households rely on unregulated private water sources such as wells, springs and streams which pose contamination risks.

With ongoing investigations and given that the causative agent of the cluster is not yet determined, there remains a level of risk attributed to the event. As such, the overall public health risk level to the affected communities is assessed as moderate.

At the national level, however, the risk is considered low due to the localized nature of the event and apparent decreasing incidence. Similarly, at the regional and global levels, the risk is low at this time.

         (Continue . . . )

 

Hawaii: DOH Launches Bird Flu Survey For Backyard Flock Owners & Bird Rescuers

 

Hawaii lies beneath the West Pacific Flyway


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Despite being located thousands of miles from the mainland - and never having previously reported HPAI -  last November Hawaii reported the detection of the H5 virus at a local (Oahu) wastewater treatment plant.  

A month later, another treatment plant on Hilo reported the virus. In between, we learned of at least two outbreaks in captive and/or wild birds on Oahu.

The good news is that genetic analysis showed that this was an older genotype (A3) - which was first detected in Alaska in 2022 - and has not been linked to human, or cattle, infection.  But it demonstrated that HPAI viruses could hitch a ride on migratory birds to a remote island chain in the middle of the Pacific. 

And if it happened once . . . it could happen again. 

While no human cases have been reported from Hawaii, serological studies (see here and here) have shown that mild (or even subclinical) H5 infections may occurring, but going undetected.  Even when testing is undertaken, there is a narrow `window' during which the virus may be detected, leading to potential false-negatives. 

The raising of backyard chickens is common in Hawaii (cite), and - much like where I live in Florida - feral chickens are a common sight. As on the mainland, the rising price of eggs may be driving more people towards raising backyard birds. 

In order to get a better handle on the the number, and practices, and bird flu awareness of backyard poultry owners - yesterday the Hawaii Dept of Health launched a (voluntary) bird flu survey for flock owners and bird rescuers.

 First the announcement, after which I'll have a bit more.

DOH LAUNCHES BIRD FLU SURVEY FOR BACKYARD FLOCK OWNERS AND BIRD RESCUERS

Posted on Mar 3, 2025 in Newsroom

HONOLULU — The Hawaiʻi State Department of Health (DOH) is inviting Hawaiʻi residents who keep backyard flocks or are involved in bird rescue, to participate in a new survey aimed at gathering important data on bird flu awareness and preparedness.

The survey will collect critical information on the understanding of bird flu, as well as the practices and needs of those who keep poultry or care for rescued birds.

“We want to better understand the potential exposures that backyard flock owners and bird rescuers face when it comes to avian influenza, so we can help prevent future human bird flu infections in partnership with the community,” said Dr. Sarah Kemble, Hawaiʻi state epidemiologist. “By reaching out through both digital and in-person methods, we hope to get wide participation and honest feedback.”

The survey will be anonymous and accessible online through the following link: https://redcap.link/birdflusurvey

Only Hawaiʻi residents who keep at least one poultry bird at home, those involved in bird rescue activities, or those having direct contact with birds in the past year for other reasons are requested to participate at this time. Residents are encouraged to complete the survey as soon as possible to help the DOH collect valuable insights.

The outreach strategy for this survey includes posting the survey link in various Facebook groups dedicated to Hawaiʻi backyard flock owners and bird rescuers. Additionally, flyers with QR codes linking to the survey will be distributed in poultry feed stores and other animal care venues across the state.

Questions about the survey or bird flu may be directed to the DOH Disease Reporting Line at 808-586-4586 or doh.docd.dib@doh.hawaii.gov. If you have symptoms and a known exposure within the past 10 days, please contact your primary care provider for evaluation and testing, as well as the DOH Disease Reporting Line for further guidance.

More information on bird flu can be found on the DOH website: https://health.hawaii.gov/docd/disease_listing/avian-influenza/

While the risks from avian flu remain low for the general population, those who have close contact with poultry, livestock, or wild birds, are at somewhat greater risk. 

The fatal H5N1 case from Louisiana and the recent hospitalized case in Wyoming both appear to have been infected via backyard and/or wild birds, while the CDC lists 2 dozen additional cases linked to poultry farms and culling operations. 

Last August the WHO published Interim Guidance to Reduce the Risk of Infection in People Exposed to Avian Influenza Viruses, which lists a number of `risk factors', including:

• keep live poultry in their backyards or homes, or who purchase live birds at markets;

• slaughter, de-feather and/or butcher poultry or other animals at home;

• handle and prepare raw poultry for further cooking and consumption; 

Similarly, PAHO (the Pan-American Health Organization) states on their Avian Influenza landing page:

Transmission

The most common way for the virus to enter a territory is through migratory wild birds. The main risk factor for transmission from birds to humans is direct or indirect contact with infected animals or with environments and surfaces contaminated by feces. Plucking, handling infected poultry carcasses, and preparing poultry for consumption, especially in domestic settings, may also be risk factors.

And over the years we've seen scores of anecdotal accounts (mostly from Asia) of H5 infections from close contact with poultry, including the latest fatal case from Cambodia. 

While the risks posed by backyard poultry are likely still very low - and can be largely mitigated by taking proper precautions - they are not zero.

Which is a lesson we really don't want to have to learn the hard way.

Frontiers Vet. Sci: Genetic Characterization of an H3N2 Canine Influenza Virus Strain in China in 2023—Acquisition of Novel Human-like Amino Acid Substitutions

Just one of many scenarios - Dogs as `mixing vessels' for Influenza


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Up until 2004, dogs (and cats) were believed largely immune to influenza A infection. For cats that perception changed after hundreds of captive cats (tigers) died from H5N1 in Southeast Asia after being fed contaminated poultry (see H5N1: Catch as Cats Can).

For dogs, it happened after an equine H3N8 virus mutated enough to spill over into  greyhounds at a Florida race track in 2004 (see EID Journal article Influenza A Virus (H3N8) in Dogs with Respiratory Disease, Florida).

A 96% match to the equine H3N8 virus, this canine H3N8 was believed to have jumped directly from horses to dogs without any reassortment.

Since then canine H3N8 has been sporadically reported across much of the United States. It is considered a `canine specific’ virus, and has not crossed back into horses. Additionally, there have been no reports of human infection.

Had that been the only instance, it might be easily dismissed. But in 2007 another virus - this time Avian H3N2 - spilled over and become endemic in dogs in South Korea (see Transmission of Avian Influenza Virus (H3N2) to Dogs).

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.

 

While the canine H3N8 virus has remained fairly stable over the past two decades, the same can't be said for the Asian H3N2 virus. We've seen numerous reports coming out of China and Korea suggesting the canine H3N2 continues to adapt and reassort 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

In April of 2015, this Asian canine H3N2 virus finally turned up in North America (see CDC Statement On H3N2 Canine Influenza In Chicago Region), and quickly spread across much of the United States over a remarkably short period of time.

 In 2017, the CDC added Canine H3N2 to their IRAT (Influenza Risk Assessment Tool) 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).

Since then, we've seen sporadic reports (mostly out of China) on a variety of reassortant H3Nx viruses, including:

Frontiers in Microb.: Emergence & Evolution of A Novel Canine-Avian Reassortant H3N2 (China)

Transboundary & Emerg. Dis.: H3 Avian Influenza Virus Isolated from China in 2021–2022 Showed the Emerging H3N8 Posed a Threat to Human Health

China: Emergence of a Novel Reassortant H3N6 Canine Influenza Virus

Follow up reports on these, and other studies out of China, are often slow in coming. But today we've another study - again from China - that finds the canine H3N2 virus continues to pick up human-flu-like amino acid substitutions which may increase its public health threat.  

Due to its length, I've only reproduced the abstract and some excerpts from the discussion. Follow the link to read the report in its entirety.  I'll have a bit more after the break. 

Genetic characterization of an H3N2 canine influenza virus strain in China in 2023—acquisition of novel human-like amino acid substitutions

Sihan Li1 Liangyu Chu1 Yancheng Zhang2 Yaxuan Yu2 Guoqing Wang2*

Around 2005, influenza A virus (IAV) once again crossed species barriers and established a stable lineage within canine populations. Currently, avian-origin H3N2 canine influenza virus (CIV) is the only strain of influenza that is stably circulating in canine populations. Initially, this virus was detected exclusively in Asian countries, such as China and South Korea. However, in 2015, it was isolated from dogs in the United States, where it subsequently caused a large-scale outbreak.

Since its initial isolation, the H3N2 CIV has demonstrated the ability to infect mammals, including cats. Throughout its spread, the virus has continuously enhanced its adaptability to mammalian hosts, posing a potential public health threat. 

To monitor the prevalence of H3N2 CIV in China, we collected 131 nasal swabs from dogs and cats with respiratory symptoms between December 2023 and February 2024 in Beijing, Changchun, Shenyang, Hohhot, and Yunfu. From these samples, one influenza virus strain was successfully isolated.

 Through whole-genome sequencing and phylogenetic analysis, this strain was identified as avian-origin H3N2 CIV. All eight gene segments exhibited amino acid substitutions, with PB2 107 N, HA1 202I, and M1 227T positions being identical to those found in the currently circulating H3N2 human influenza virus (HuIV). Interestingly, by around 2021, the H3N2 HuIV had already completed the PB2 107 N substitution. 

Our study indicates that H3N2 CIV is evolving toward increased adaptability to mammalian hosts, highlighting the necessity for strengthened monitoring and risk assessment.

(SNIP)


CIV-CC23 has acquired 3 novel human-like amino acid substitutions compared to the preceding H3N2 CIV strains. This findings suggest that H3N2 CIV evolves over time, and if it accumulates a sufficient number of human-like amino acid substitutions, it may acquire the ability to efficiently propagate in humans. Among these substitutions, PB2 107 N is an amino acid change that occurred in H3N2 HuIV around 2021. Almost all H3N2 AvIV and previous H3N2 CIV isolates have been PB2 107S, making the emergence of this substitution in CIV-CC23 noteworthy.

While the precise impact of this substitution on H3N2 CIV’s adaptation to mammals remains unclear, PB2 is known to play a significant role in enhancing IAV adaptation to mammals. For example, PB2 E627K increases the virus’s polymerase activity, facilitating replication in mammalian cells (9). Similarly, PB2 S714I in H3N2 CIV has been shown to enhance RNP complex activity, virus replication, and pathogenicity in mice (26). Given our limited sample size, it remains uncertain whether PB2 107 N will be prevalent in future H3N2 CIV. This requires broader temporal and geographic monitoring to obtain a sufficient sample size. However, the relationship between mammalian adaptive changes and human-like amino acid substitutions in H3N2 CIV warrants further investigation.

Our study indicates that H3N2 CIV continues to circulate in canine populations in China, persistently acquiring human-like amino acid substitutions, which poses a potential public health risk. Therefore, a comprehensive surveillance system for H3N2 CIV should be established, with collaboration among animal hospitals, shelters, and pet trade markets nationwide. Nasal swab samples should be collected from dogs and cats presenting with respiratory symptoms to facilitate broader and more diverse studies on virus prevalence and host specificity. Additionally, it is essential to enhance monitoring and management of companion animal transportation and strengthen risk assessment for H3N2 CIV to better understand the zoonotic potential of the currently circulating strain.

         (Continue . . . )

 

While we spend a lot of time looking at HPAI H5 or H7 avian viruses that might spark a pandemic - mostly because of their much higher fatality rates in humans - history suggests (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?) that H1, H2, or H3 (avian/swine/canine) novel flu viruses are more likely to spark a human pandemic.

For some other blogs on canine reassortment possibilities, you may wish to revisit:

Nature: Adaptation Potential of H3N8 Canine Influenza Virus in Human Respiratory Cells

Viruses Review: Potential Intermediates in the Cross-Species Transmission of Influenza A Virus to Humans

One Health Adv.: Surveillance & Characterization of Avian-origin H3N2 Canine Influenza Viruses (China 2021)

Viruses: Zoonotic Animal Influenza Virus and Potential Mixing Vessel Hosts

Increased Public Health Threat of Avian-origin H3N2 Influenza Virus During Evolution in Dogs (Revisited)