Immunopathogenesis of lethal H5N1 avian influenza virus clade 2.3.4.4b infection in macaques
The H5N1 avian influenza virus clade 2.3.4.4b outbreak represents a major pandemic threat for humans, with some reported cases of severe and fatal respiratory illness. A key unanswered question is the pathogenesis of severe H5N1 disease following respiratory infection. In this study, we explored mechanisms of pathogenesis of severe H5N1 disease in cynomolgus and rhesus macaques following infection with the H5N1 isolate A/Texas/37/2024 (huTX37-H5N1). Cynomolgus macaques developed severe pneumonia that was lethal in 100% of macaques by 7 days post-infection. By contrast, rhesus macaques demonstrated dose-dependent mortality, and surviving animals showed protective immunity against high-dose re-challenge. A multi-omics analysis demonstrated that H5N1 infection was characterized by robust induction of proinflammatory cytokines, innate immune cells, complement, coagulation, apoptosis, and immune exhaustion pathways. Taken together, our data indicate inflammation and immune dysregulation as key mechanisms of H5N1 pathogenesis in nonhuman primates.
Authors
- Lisbeth Ramírez-Carvajal
- Colin Henderson
- Daniel Valentin
- Ninaad Lasrado (ORCID: https://orcid.org/0000-0001-6762-2654)
- Mehtap Cabus
- Brandon Narvaez
- Jason Velasco
- Soumen Paul (ORCID: https://orcid.org/0000-0002-4752-4800)
- Malika Aïd (ORCID: https://orcid.org/0000-0002-4498-7893)
- Christopher Kitajewski
- Clarissa M. Koch (ORCID: https://orcid.org/0000-0002-7424-6009)
- Antônio José Piantino Ferreira (ORCID: https://orcid.org/0000-0002-0086-5181)
- Claire E. Lyons (ORCID: https://orcid.org/0000-0002-2842-146X)
- Tatyana Orekov
- Mark G. Lewis (ORCID: https://orcid.org/0000-0001-7852-0135)
- Elyse Teow
- Dan H. Barouch (ORCID: https://orcid.org/0000-0001-5127-4659)
- Swagata Kar (ORCID: https://orcid.org/0000-0003-3702-6207)
- Martin H. Koldijk
- Robert R. Campbell
- Brad Finneyfrock
- Rebecca Stone (ORCID: https://orcid.org/0000-0002-6172-4358)
- S Rivas (ORCID: https://orcid.org/0000-0002-0424-7970)
- Amanda J. Martinot (ORCID: https://orcid.org/0000-0001-6237-6191)
- Laurent Pessaint (ORCID: https://orcid.org/0000-0002-2126-3008)
- Joost Haasnoot
- Jake Yalley-Ogunro
- Maciel Porto (ORCID: https://orcid.org/0000-0002-3427-454X)
- Joseph P. Nkolola (ORCID: https://orcid.org/0000-0002-0678-9765)
- Katelyn Kouneski
- Jonathan Stone
- Anthony Cook
- Jaap Goudsmit
- Hanné Andersen
- M. Peterson
- Grishma Patel (ORCID: https://orcid.org/0009-0003-9579-2687)
- Alex Van Ry
- Wilfred Beah
- Autumn Berlied
Institutions
- Leiden University (NL)
- Tufts University (US)
- Beth Israel Deaconess Medical Center (US)
- Harvard University (US)
- Bioqual (US)
Publication Details
- Journal
- Immunity
- Published
- 2025-08-18
- DOI
- https://doi.org/10.1016/j.immuni.2025.07.020
- Citations
- 6
- Primary Topic
- Influenza Virus Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 8.13