Evidence map›Paper›PMID 42466872›Full record

ArticleMicrobiology spectrum2026

Cellular tropism of highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b viruses in human respiratory and bovine mammary epithelial cells.

Nicole Brock, Hui Zeng, Claudia Pappas, Troy J Kieran, Xiangjie Sun, Joanna A Pulit-Penaloza, Terrence M Tumpey, Taronna R Maines, Jessica A Belser

Abstract read
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In one paragraph

Article in Microbiology spectrum, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Nicole Brock *Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Hui Zeng *Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Claudia PappasImmunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Troy J KieranImmunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Xiangjie SunImmunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.ORCID 0000-0002-9872-1337
Joanna A Pulit-PenalozaImmunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.ORCID 0000-0002-2187-5872
Terrence M TumpeyImmunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Taronna R MainesImmunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.ORCID 0000-0002-4097-6724
Jessica A BelserImmunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.ORCID 0000-0002-0755-7368

Funding

U.S. Department of Health and Human Services
6 · The paper itself

Abstract

The recent introduction and spread of HPAI A(H5N1) clade 2.3.4.4b viruses to U.S. dairy cattle demonstrate their ability to adapt to new mammalian hosts. Although multiple A(H5N1) genotypes have caused human infections, only two clade 2.3.4.4b genotypes (B3.13 and D1.1) have been detected in cattle, suggesting clade- or genotype-specific tropism. Understanding how these viruses replicate in human airway and bovine mammary epithelial cells is important for assessing viral evolution, mammalian adaptation, and associated public health risks. Here, we characterized replication kinetics and immune gene expression in human bronchial epithelial (Calu-3) cells and bovine mammary epithelial (MAC-T) cells infected with A(H5N1) clade 2.3.4.4b human isolates representing the B3.13, D1.1, and B3.2 genotypes, an A(H5N1) clade 1 virus, and an A(H1N1)pdm09 strain. All viruses replicated efficiently in Calu-3 cells, although replication was delayed at 33°C compared to 37°C. Clade 2.3.4.4b viruses induced moderate expression of type I interferon and proinflammatory response in Calu-3 cells, but at lower levels than the A(H1N1)pdm09 and A(H5N1) clade 1 strains. Replication and immune activation varied markedly among clade 2.3.4.4b genotypes in MAC-T cells. B3.13 viruses achieved higher titers and triggered stronger induction of innate immune response genes than other A(H5N1) genotypes or clades. These findings indicate genotype- and cell type-specific differences in replication and host responses, with B3.13 showing enhanced tropism in bovine mammary cells, consistent with adaptation that may elevate zoonotic risk. Our results highlight the value of comparative studies across host cell types and diverse viral isolates to inform risk assessments for emerging influenza viruses. IMPORTANCE: Influenza A viruses cross species barriers through a combination of factors, including the ability to bind to and infect permissive cells, replicate efficiently, and modulate host immune responses. Since 2024, A(H5N1) clade 2.3.4.4b viruses have continued to evolve, infecting a broad range of avian and mammalian species, including cattle in the United States, and causing sporadic human infections. Here, we evaluated a panel of A(H5N1) clade 2.3.4.4b viruses isolated from humans to assess their replication and host responses in two relevant mammalian cell types: human bronchial epithelial cells and bovine mammary gland epithelial cells. While all genotypes replicated efficiently in human bronchial epithelial cells, only B3.13 viruses showed strong replication and broad host response induction in bovine mammary epithelial cells. These results underscore variation in evolution, tissue tropism, and host adaptation among A(H5N1) clade 2.3.4.4b viruses and highlight the need for continued surveillance and close monitoring of B3.13 genotype viruses.

Indexed as

Epithelial CellsInfluenza A Virus, H5N1 SubtypeInfluenza, HumanMammary Glands, AnimalViral TropismAnimalsCattleCell LineFemaleGenotypeHumansInfluenza A Virus, H1N1 SubtypeVirus Replicationhost responseinfluenzain vitrotropism

Identifiers

PMID42466872
PMCPMC13436365

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.