Comprehensive Study on H5 Influenza

Article Title: Replication kinetics, pathogenicity and virus-induced cellular responses of cattle-origin influenza A(H5N1) isolates from Texas, United States

by Mostafa et al 2025

https://www.tandfonline.com/doi/full/10.1080/22221751.2024.2447614#abstract

Using the criteria from this checklist (listed in bold) by Plos.org: https://plos.org/resource/peer-review-checklist/ 

Why I choose this article:

In my career, I have done a lot of work with public health surveillance.  The evolution of the H5 Influenza viruses (or bird flu) is worthy of attention.  The fact that now the H5 viruses are impacting the dairy industry is concerning as previously it was only found in birds. 

What I thought the article was about before I read it:

They did a study in cattle in Texas looking at the movement or spread of the H5 influenza virus and the effect on cellular responses in cattle to test the impact of the H5 virus on cattle.  Mostly the article headlines listed that the anti-virals were still effective against the H5 strain.

Disclaimer: This review is my opinion only and not intended as an official review.

-Identify the research question and key claims

Key claims from the abstract in laymen’s terms:  The human H5 Influenza A replicated more efficiently than cattle h5 Influenza A in mammal and bird cells.  Variations in the proteins associated with H5 Influenza A from this study don’t impact the ability of anti-viral medications that inhibit PA proteins and Neuraminidase (NA) to treat patients. 

The research question listed at the end of the abstract is as follows: “Our results highlight the potential risk of HPAIV H5N1 virus adaptation in human and/or dairy cattle during the current multistate/multispecies outbreak in the US.(1)”

-Think about context and related literature

Given the state of the infections in the human (mostly dairy/cattle workers) that have acquired the H5 Influenza A virus is so far relatively mild (low risk (2) according to public health authorities like the CDC) and not showing strong infectivity from person to person(2), this study is consistent with my preconceived notions. 

-Look at the figures and tables. Are they clear? Do they represent what the study is about?

The figures clearly outline the work done in this study.  The amino acid substitutions in the different strains were illustrated well.  The use of tissue staining in key tissues was important to demonstrate the concern with neurological symptoms in some of the animal hosts that get infected with H5.  And the testing of antivirals was especially useful.  I would have loved to see some comparison with a currently circulating strand of influenza in some of the antiviral tests; I’m sure that is well documented in literature and easy to look up as needed.

-Examine the results. Are they supported by the data?

The results are carefully examined and supported with the data. 

In figure 4 (1) I was surprised to see low infectivity in the mammary glands.  Given the transmission of H5 in dairy milk.  This is most like due to the model that was used, as mice have biological differences compared to humans and cattle.  Overall, it was important to prove that there was increased H5 in the lungs and that was obvious in the data.  Given the concerns with neurological symptoms in other mammalian hosts, it is understandable why the study did several tests with brain and lung tissue.  I especially appreciated the immunological markers in figure 7 (1) they studied for cytokines and chemokines, indicating the increased immune responses in the mice.

-Read the conclusions. Do they make sense?

Yes, the conclusion that H5 should be closely monitored is valid.  They also indicated that the potential adaptations in the human strains should be monitored as well, as it seems that the strain of H5 in cattle was less concerning.  It’s comforting that the anti-virals are still effective and the risks of an H5 outbreak are low for now.

-Check the methods. Are they appropriate and reproducible?

There is a comprehensive list of the method details.  That appear appropriate and reproducible on the surface.

Amy’s notes:

How would you read this if you applied a biased lens?

If I was viewing this through an anti-science lens, it would be easy to confirm that any out breaks can easily be treated with anti-virals in this study.  Although, I was surprised by the amount of data that was in this study.  So, looking just for the data on anti-virals would take some digging.  An additional layer to this thought approach would be to confirm that the use of vaccines was unnecessary and the fact that the anti-viral medications are still effective would support that assumption.

Here’s my counter thoughts: Only an average of 50% of the US population gets an influenza vaccine yearly.  This is important to consider when reading about treatment options in scientific studies, since often in pandemics treatment options get quickly depleted. In this article by Worobey et al 20143, one of the theories for explaining the severity of the 1918 H1N1 Spanish Flu is that most of the 20-year-olds that died during that pandemic were not exposed to the H1 Influenza strain.  The predominant flu strain was an H3 Influenza. There was a huge shift in the Influenza virus that contributed to the 1918 Spanish Flu’s death toll.  This potential shift to an H5 Influenza strain is concerning for similar reasons.  As updates are made to the flu vaccine yearly, it’s important to make sure you are protected against the most commonly circulating influenza strains to prevent future infections, even if you prevent an infection several years later.  If you are concerned about vaccines, there are still things you can do to keep yourself healthy during respiratory season.  Stay home and rest when you are sick, wash your hands frequently, wear a mask if you are going to be in crowed places. 

Amy Fuller, MS, ASCP(MLS)CM SMCM

Owner, Clinical Insights LLC

References:

1.    Mostafa, A., Barre, R. S., Allué-Guardia, A., Escobedo, R. A., Shivanna, V., Rothan, H., … Martinez-Sobrido, L. (2025). Replication kinetics, pathogenicity and virus-induced cellular responses of cattle-origin influenza A(H5N1) isolates from Texas, United States. Emerging Microbes & Infections, 14(1). https://doi.org/10.1080/22221751.2024.2447614

2.    CDC.gov (Feb 2025). Retrieved from https://www.cdc.gov/bird-flu/situation-summary/index.html on 17 Feb 25.

3.    Worobey M, Han GZ, Rambaut A. Genesis and pathogenesis of the 1918 pandemic H1N1 influenza A virus. Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):8107-12. doi: 10.1073/pnas.1324197111. Epub 2014 Apr 28. PMID: 24778238; PMCID: PMC4050607.