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Volume 32, Number 5—May 2026

Dispatch

Replication Efficiency of Contemporary Highly Pathogenic Avian Influenza A(H5N1) Virus Isolates in Human Nasal Epithelium Model

Meaghan Flagg1, Christopher J. Winski1, Bridget G. Brackney, Tessa R. Lutterman, Johan A. Ortiz-Morales2, Brandi N. Williamson, and Emmie de WitComments to Author 
Author affiliation: Author affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA

Main Article

Table

Influenza A virus isolates used in study of replication efficiency of contemporary highly pathogenic avian influenza A(H5N1) virus isolates in human nasal epithelium model*

Isolate Subtype Clade Genotype Known mammalian adaptions Symptoms, disease
severity		 References GISAID identifier
A/Brisbane/59/2007
 H1N1
 NA
 NA
 PB2 E627K
 Unknown
 (5)
 EPI_ISL_356921
A/New York/470/2004
 H3N2
 NA
 NA
 PB2 E627K
 Unknown
 (6)
 EPI_ISL_8959
A/Vietnam/1203/2004
 H5N1
 1
 NA
 PB2 E627K
 Severe respiratory distress resulting in fatality
 (7)
 NCBI: txid284218
A/Texas/37/2024
 H5N1
 2.3.4.4b
 B3.13
 PB2 E627K
 Mild respiratory symptoms and conjunctivitis
 (2)
 EPI_ISL_19027114
A/bovine/Ohio/B24-OSU-342/2024
 H5N1
 2.3.4.4b
 B3.13
 PB2 M631L
 NA
 (8)
 EPI_ISL_19178076
A/mountain lion/MT/1/2024
 H5N1
 2.3.4.4b
 B3.6
 None
 Mountain lion found dead
 (9)
 EPI_ISL_19083124
A/Wyoming/01/2025 H5N1 2.3.4.4b D1.1 PB2 E627K Severe respiratory disease requiring hospitalization https://www.cdc.gov/bird-flu/spotlights/
h5n1-response-02262025.html EPI_ISL_19749443
A/Nevada/10/2025 H5N1 2.3.4.4b D1.1 PB2 D701N Conjunctivitis EPI_ISL_19726293

*All virus isolates were sequenced and found to be identical to sequences deposited in GISAID (https://www.gisaid.org) or GenBank. NCBI, National Center for Biotechnology Information; NA, not available; PB, polymerase basic.

Main Article

References
  1. Rolfes  MA, Kniss  K, Kirby  MK, Garg  S, Reinhart  K, Davis  CT, et al. Human infections with highly pathogenic avian influenza A(H5N1) viruses in the United States from March 2024 to May 2025. Nat Med. 2025;31:3889–98. DOIPubMedGoogle Scholar
  2. Uyeki  TM, Milton  S, Abdul Hamid  C, Reinoso Webb  C, Presley  SM, Shetty  V, et al. Highly pathogenic avian influenza A(H5N1) virus infection in a dairy farm worker. N Engl J Med. 2024;390:2028–9. DOIPubMedGoogle Scholar
  3. van Riel  D, den Bakker  MA, Leijten  LM, Chutinimitkul  S, Munster  VJ, de Wit  E, et al. Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses. Am J Pathol. 2010;176:1614–8. DOIPubMedGoogle Scholar
  4. Deprez  M, Zaragosi  LE, Truchi  M, Becavin  C, Ruiz García  S, Arguel  MJ, et al. A single-cell atlas of the human healthy airways. Am J Respir Crit Care Med. 2020;202:1636–45. DOIPubMedGoogle Scholar
  5. WHO Collaborating Centre for Reference and Research on Influenza. Characteristics of human influenza AH1N1, AH3N2, and B viruses isolated September 2007 to February 2008. London: The Centre; 2008.
  6. Memoli  MJ, Jagger  BW, Dugan  VG, Qi  L, Jackson  JP, Taubenberger  JK. Recent human influenza A/H3N2 virus evolution driven by novel selection factors in addition to antigenic drift. J Infect Dis. 2009;200:1232–41. DOIPubMedGoogle Scholar
  7. Maines  TR, Lu  XH, Erb  SM, Edwards  L, Guarner  J, Greer  PW, et al. Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals. J Virol. 2005;79:11788–800. DOIPubMedGoogle Scholar
  8. Zhang  L, Lai  Y, Cui  Y, Yang  Q, Shao  Y, Ding  S, et al. Emergence of mammalian-adaptive PB2 mutations enhances polymerase activity and pathogenicity of cattle-derived H5N1 influenza A virus. Nat Commun. 2025;17:1011. DOIPubMedGoogle Scholar
  9. Kaiser  F, Morris  DH, Wickenhagen  A, Mukesh  R, Gallogly  S, Yinda  KC, et al. Inactivation of avian influenza A(H5N1) virus in raw milk at 63°C and 72°C. N Engl J Med. 2024;391:90–2. DOIPubMedGoogle Scholar
  10. Flagg  M, Williamson  BN, Ortiz-Morales  JA, Lutterman  TR, de Wit  E. Comparison of contemporary and historic highly pathogenic avian influenza A(H5N1) virus replication in human lung organoids. Emerg Infect Dis. 2025;31:318–22. DOIPubMedGoogle Scholar
  11. Tan  KS, Liu  J, Andiappan  AK, Lew  ZZR, He  TT, Ong  HH, et al. Unique immune and other responses of human nasal epithelial cells infected with H5N1 avian influenza virus compared to seasonal human influenza A and B viruses. Emerg Microbes Infect. 2025;14:2484330. DOIPubMedGoogle Scholar
  12. Zeng  H, Goldsmith  CS, Kumar  A, Belser  JA, Sun  X, Pappas  C, et al. Tropism and infectivity of a seasonal A(H1N1) and a highly pathogenic avian A(H5N1) influenza virus in primary differentiated ferret nasal epithelial cell cultures. J Virol. 2019;93:e00080–19. DOIPubMedGoogle Scholar
  13. Zhang  X, Lam  SJ, Chen  LL, Fong  CH, Chan  WM, Ip  JD, et al. Avian influenza virus A(H5N1) genotype D1.1 is better adapted to human nasal and airway organoids than genotype B3.13. J Infect Dis. 2026;233:e662–6. DOIPubMedGoogle Scholar
  14. Restori  KH, Weaver  V, Patel  DR, Merrbach  GA, Septer  KM, Field  CJ, et al. Preexisting immunity to the 2009 pandemic H1N1 virus reduces susceptibility to H5N1 infection and disease in ferrets. Sci Transl Med. 2025;17:eadw4856. DOIPubMedGoogle Scholar
  15. Mellis  AM, Coyle  J, Marshall  KE, Frutos  AM, Singleton  J, Drehoff  C, et al. Serologic evidence of recent infection with highly pathogenic avian influenza A(H5) virus among dairy workers—Michigan and Colorado, June–August 2024. MMWR Morb Mortal Wkly Rep. 2024;73:1004–9. DOIPubMedGoogle Scholar

Main Article

1These authors contributed equally to this article.

2Current affiliation: LSU Health, Shreveport, Louisiana, USA.

Page created: April 14, 2026
Page updated: May 01, 2026
Page reviewed: May 01, 2026
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