Wednesday, March 26, 2025

Virology: Detection of Antibodies Against Influenza A Viruses in Cattle

 

#18,393

A year ago today, in the wake of the surprise announcement of the first detection of H5N1 in dairy cows in Texas and Kansas, I wrote A Brief History Of Influenza A In Cattle/Ruminantswhere we looked at a number of past papers on both influenza and influenza-like illnesses in cattle and goats.

In some cases, viruses were identified, while in other cases they were not. So, while the detection of H5 in cattle may have been unexpected, it wasn't entirely without precedents. 

Since then, HPAI H5 has turned up in hundreds of cattle herds, along with sporadic spillovers into goats, alpacas, pigs, and most recently a sheep in the UK.  Quite frankly, the more we look, the more we find that H5 in livestock is more common than we knew. 

All of which brings us to a new study, published this week in Virology, which looks for IAV antibodies in United States cattle in the year prior to the discovery of H5N1 in dairy cows.  And once again, we find that evidence of (non-H5) IAV infection was common across a wide sampling of serum samples taken in 2023 and early 2024. 

Of particular note, this study found that IAV infection isn't limited to lactating dairy cows Male cattle (bulls and steers) were just as likely to carry antibodies to IAV as cows and heifers.

For the past year, we've seen a continued reluctance to test beef cattle for H5N1, using the rationale that cattle are generally not susceptible to IAV infection, and H5 has a special affinity for lactating cows

Since beef cattle are only rarely tested, they maintain their `clean record', and are therefore not considered `high risk. Essentially the same reasoning that delayed the testing of dairy cattle for H5N1 for several months in early 2024, which probably gave the virus more time to spread. 

Today's report is well worth reading in its entirety, as it raises serious questions about how widespread IAV infection truly is in bovine species, and should inspire even greater scrutiny of other livestock species (both here in the United States, and around the globe). 

Detection of antibodies against influenza A viruses in cattle

Authors: Yuekun Lang, Lei Shi, Sawrab Roy, Dipali Gupta, Chao Dai, Muhammad Afnan Khalid, Michael Z. Zhang, Shuping Zhang, Xiu-Feng Wan, Richard Webby, Wenjun Ma wma@missouri.eduAuthors Info & Affiliations

https://doi.org/10.1128/jvi.02138-24

ABSTRACT

Unexpected outbreaks caused by the H5N1 highly pathogenic avian influenza virus (HPAIV) in dairy cows in the United States (US) have raised significant veterinary and public health concerns. When and how the H5N1 HPAIV was introduced into dairy cows and the broader epidemiology of influenza A virus (IAV) infections in cattle in the US remain unclear.

Herein, we performed a retrospective study to screen more than 1,700 cattle serum samples collected from different bovine breeds in the US from January 2023 to May 2024 using an enzyme-linked immunosorbent assay (ELISA) targeting the nucleoprotein (NP) to detect IAV infections, and the positive samples were further tested by hemagglutination inhibition (HI) assay. 

Results showed that 586 of 1,724 samples (33.99%) from 15 US states were seropositive by the NP ELISA assay, including 78 samples collected in 2024 and 508 samples collected in 2023. Moreover, the HI assay revealed that 45 of these ELISA-positive samples were positive to human seasonal H1N1 and H3N2 and swine H3N2 and H1N2 viruses, and some were positive to two or three tested IAVs. 

Surprisingly, none of these ELISA-positive samples were HI positive for the circulating bovine H5N1 strain. Our results demonstrate that IAVs other than H5N1 can infect cattle, infections are not limited to dairy cows, and that bovine infections with swine and human IAVs have occurred prior to the H5N1 outbreaks. All results highlight the value in monitoring IAV epidemiology in cattle, as the viruses might adapt to cattle and/or reassort with the currently circulating H5N1 HPAIV, increasing risk to humans.

IMPORTANCE

Influenza A virus (IAV) is an important zoonotic pathogen that can infect different species. Although cattle were not historically considered vulnerable to IAV infections, an unexpected outbreak caused by H5N1 highly pathogenic avian influenza virus in dairy cows in the United States (US) in early 2024 has raised significant concerns. When and how the virus was introduced into dairy cows and the wider impact of IAV infections in cattle in the US remain unclear. Our retrospective serological screen provided evidence of human and swine H1 and H3 IAV infections in different cattle breeds in addition to dairy cows, although no H5N1 infection was detected. Our results underline the necessity to monitor IAV epidemiology in cattle, as reassortment of IAVs from different species may occur in cattle, generating novel viruses that pose threats to public and animal health.

         (SNIP) 

We identified several serum samples that were HI-positive to both swine and human IAVs. Considering the potential cross-reaction between seasonal huH1N1 and swH1N2v and seasonal huH3N2 and cluster I swH3N2 viruses, we retested seasonal huH1N1 HI-positive samples against the swH1N2v and cluster I swH3N2 HI-positive samples against the seasonal huH3N2 virus and vice versa. The results confirmed that no cross HI titer was detected in these samples (Table S1), indicating that IAV dual or triple infections in cattle appear to be genuine. Notably, one sample was HI-positive to both cluster I swH3N2 and seasonal huH1N1 viruses, while another sample was positive for cluster I swH3N2, seasonal huH3N2 and huH1N1 viruses.
These findings indicate that co-infection with IAVs might occur in some individual cattle. Considering that the H5N1 HPAIV is circulating in dairy cattle herds (8) and cattle can be infected with human and swine IAVs, reassortment of IAVs from different species might happen in cattle (10), generating novel genotypes of H5Nx virus with pandemic potential or at least with increased ability for zoonotic transmission.

In summary, our retrospective serological study demonstrated that IAVs other than H5N1 HPAIV are able to infect different breeds of cattle regardless of their gender and age. Therefore, IAV infection in cattle is likely more complicated than recognized. It is necessary to monitor bovine IAV epidemiology through systematic influenza surveillance to prevent IAV adaptation and potential reassortment that would increase the threat to public health.

(Continue . . . )


While this new information should inspire a paradigm shift in the way we deal with IAV in livestock, we have a long history of denying potential health threats and of maintaining the status quo when facts are either inconvenient, expensive, or difficult to deal with. 

But at least with the help of this kind of research, we'll know why we failed.