Friday, June 13, 2025

mBio: Outcomes of Experimental Infection of Calves with Swine Influenza H3N2 Virus

  

#18,755

Until about 15 months ago, the scientific consensus was that cattle - and ruminants in general - weren't highly susceptible to Influenza A Viruses (IAV). As a result, when cattle began to fall ill in Texas in early 2024, it took months before anyone thought to test them for HPAI H5 avian influenza.

There had been clues over the years, however, suggesting that cattle weren't completely resistant, many of which I covered in A Brief History Of Influenza A In Cattle/Ruminants.

Not only had German researchers successfully infected cattle with H5N1 as far back as 2008, cattle (and pigs) are both highly susceptible to IDV (Influenza D Viruses) which may also be zoonotic (see Serological Evidence Of Influenza D Among Persons With & Without Cattle Exposure).
Since March of 2024 we've seen more than 1,070 U.S. Dairy herds infected with HPAI H5N1, and scattered reports of HPAI H5 in other livestock including goats, alpacas, pigs, and most recently a sheep in the UK.

For most of 2024 the assumption (based on limited evidence) was that there was something `special' about the B3.13 genotype of H5N1, that allowed it to infect cattle.  Internationally, many countries - which had never reported that  specific genotype - felt there was no pressing need to test their cattle

But in recent months we've seen another genotype (D1.1) turn up in Dairy cattle in 2 different states (Nevada & Arizona), along with a report last year from (Germany: FLI Statement On Experimental Infection Of Dairy Cows With European H5N1 Virus) that showed other genotypes could infect cattle as well.

While the prevailing theory has been that HPAI mainly affects lactating dairy cows - and is due to the virus's affinity to bovine mammary cells - one study last March (see Virology: Detection of Antibodies Against Influenza A Viruses in Cattle) reported that bulls and steers were just as likely to carry antibodies to (non-HPAI H5) IAV as cows and heifers.

Earlier this month we saw another study (see EID Journal: Evidence of Viremia in Dairy Cows Naturally Infected with Influenza A Virus, California, USA) which suggests a more systemic infection of cattle with IAV.

Today we travel a bit further down that line of inquiry with a new study - published this week in mBio - that finds that calves are susceptible to intranasal infection with the swine H3N2 virus, and that the virus can infect replicate in bovine respiratory and mammary gland cells.

In brief, the authors reported:

Results showed that avian H5N1 and H9N2, and swine H3N2 IAVs could infect beef cattle primary nasal turbinate and tracheal epithelial cells, as well as immortalized mammary gland epithelial cells and fibroblasts. Moreover, the swine H3N2 could infect the calves through intranasal infection, but not through oral infection, despite no obvious clinical signs and efficient transmission being observed

While swine H3N2 produced only mild or subclinical symptoms, and did not transmit efficiently among contact animals, these findings suggest that other IAV subtypes could infect and replicate in cattle.

Due to its length, I've only posted the abstract and an excerpt from the discussion. You'll want to follow the link to read it in its entirety.   

I'll return with a brief postscript after the break.

Outcomes of experimental infection of calves with swine influenza H3N2 virus

Authors: Lei Shi, Yuekun Lang, Sawrab Roy, Zhenyu Shen, Dipali Gupta, Chao Dai, Muhammad Afnan Khalid, William J. Mitchell, Shuping Zhang, Richard Webby Juergen Richt Wenjun Ma  wma@missouri.eduAuthors Info & Affiliations

PDF/EPUB

ABSTRACT

Unprecedented outbreaks caused by the H5N1 highly pathogenic avian influenza virus (HPAIV) among dairy cows in the United States have raised significant concerns. Whether other subtypes of influenza A viruses (IAVs) can infect and transmit in cattle remains largely unknown. Herein, we infected cattle respiratory and mammary gland cells with different IAVs and two groups of Holstein calves intranasally or orally with a swine H3N2 virus to determine their susceptibility. Naive calves were co-housed with infected animals to investigate virus transmission. 

Results showed that tested swine and avian IAVs could infect cattle primary nasal turbinate and tracheal epithelial cells, as well as immortalized mammary gland epithelial cells and fibroblasts. No obvious clinical signs, including fever, were observed in infected and contact calves, but macroscopic lung lesions were found in necropsied animals n both groups on day 5 post-infection. Viral shedding was detected in three out of four nasally infected calves but not in orally infected or the two groups of contact animals. 

Interestingly, viral RNA and antigen could not be detected in all tissues from individual necropsied animals from either infection group, but viral RNA and sequences were detected in serum samples of two nasally infected calves on day 7 post-infection, not on other days and in other animals. Additionally, only the nasally infected animals seroconverted. Our results indicate that in addition to H5N1 HPAIV, swine H3N2 virus can infect cattle but does not transmit efficiently among them, suggesting that other subtypes of IAVs could infect and replicate in cattle.

(SNIP)

To date, human- and swine-origin H3N2 and H1N1, as well as HPAIV H5N1 IAVs, have been documented to infect cattle, indicating that co-infection in some individual cattle with two or more IAVs might occur. Indeed, human H3N2 and H1N1 antibodies were detected in cattle herds in Northern Ireland and the United Kingdom that showed outbreaks of respiratory disease, milk drop syndrome, or diarrhea (9, 24, 27).
Our recent retrospective serological studies found that some individual cattle were double or triple infected by human seasonal and swine IAVs (22). Nevertheless, IAVs from different species, including human and swine H1 and H3 viruses as well as HPAIV H5N1, can infect cattle, which has raised significant concern that reassortment might occur in cattle to generate novel reassortant H5 viruses with internal genes from human seasonal or North American triple reassortant swine IAVs.
These novel reassortant viruses could more readily adapt to humans and other species and potentially cause the next pandemic if they gain human-to-human transmission. Therefore, it is necessary to perform systemic surveillance to monitor the epidemiology of IAVs in cattle to prevent potential further adaptation and pandemics in humans.

       (Continue . . . )

A recent study suggests the HPAI virus is far more widespread in livestock than has been reported (see Nature: A Mathematical Model of H5N1 Influenza Transmission in US Dairy Cattle).

The USDA's Dairy Herd Status Program website was updated last week, and shows just 108 herds (out of an est. 36,000) from 20 states enrolled in the voluntary herd monitoring program.

Many farmers - fearing quarantines and economic losses - simply prefer a `Don't Test, Don't Tell' strategy.  We've also seen farm workers reluctant to report illnesses, or be tested for the virus, over fears of losing their jobs (see EID Journal: Avian Influenza A(H5N1) Virus among Dairy Cattle, Texas, USA).

As a result, we don't really have a good handle on the extent and risks from IAV infection in cattle, and other livestock, here in the United States or around the world.  

While we may get away with wearing blinders for a time - and H5N1 may yet fizzle - allowing a growing array of zoonotic viruses to spread unfettered and unmonitored in livestock is a risky strategy.

One that will be hard to justify if one of them reassorts, and begins a world tour sometime in the future.