tetano
Editor, Senior Moderator
Immunity
. 2025 Aug 13:S1074-7613(25)00329-2.
doi: 10.1016/j.immuni.2025.07.020. Online ahead of print. Immunopathogenesis of lethal H5N1 avian influenza virus clade 2.3.4.4b infection in macaques
Hanne Andersen[SUP] 1 [/SUP], Malika Aid[SUP] 2 [/SUP], Jonathan J Stone[SUP] 3 [/SUP], Claire E Lyons[SUP] 3 [/SUP], Autumn Berlied[SUP] 3 [/SUP], Joseph Nkolola[SUP] 2 [/SUP], Ninaad Lasrado[SUP] 2 [/SUP], Max Peterson[SUP] 1 [/SUP], Laurent Pessaint[SUP] 1 [/SUP], Christopher Kitajewski[SUP] 1 [/SUP], Jake Yalley-Ogunro[SUP] 1 [/SUP], Maciel Porto[SUP] 1 [/SUP], Rebecca Stone[SUP] 1 [/SUP], Mehtap Cabus[SUP] 1 [/SUP], Daniel Valentin[SUP] 1 [/SUP], Alex Van Ry[SUP] 1 [/SUP], Brandon Narvaez[SUP] 1 [/SUP], Tatyana Orekov[SUP] 1 [/SUP], Swagata Kar[SUP] 1 [/SUP], Elyse Teow[SUP] 1 [/SUP], Katelyn Kouneski[SUP] 1 [/SUP], Abismel Ferreira[SUP] 1 [/SUP], Jason Velasco[SUP] 1 [/SUP], Robert Campbell[SUP] 1 [/SUP], Colin Henderson[SUP] 1 [/SUP], Wilfred Beah[SUP] 1 [/SUP], Grishma Patel[SUP] 1 [/SUP], Brad Finneyfrock[SUP] 1 [/SUP], Anthony Cook[SUP] 1 [/SUP], Soumen Paul[SUP] 1 [/SUP], Joost Haasnoot[SUP] 4 [/SUP], Lisbeth Ramirez-Carvajal[SUP] 4 [/SUP], Martin H Koldijk[SUP] 4 [/SUP], Sagrario Arias Rivas[SUP] 4 [/SUP], Clarissa M Koch[SUP] 4 [/SUP], Jaap Goudsmit[SUP] 5 [/SUP], Mark G Lewis[SUP] 1 [/SUP], Amanda J Martinot[SUP] 3 [/SUP], Dan H Barouch[SUP] 6 [/SUP]
Affiliations
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.
Keywords: H5N1; immunity; influenza; macaque; pathogenesis.
. 2025 Aug 13:S1074-7613(25)00329-2.
doi: 10.1016/j.immuni.2025.07.020. Online ahead of print. Immunopathogenesis of lethal H5N1 avian influenza virus clade 2.3.4.4b infection in macaques
Hanne Andersen[SUP] 1 [/SUP], Malika Aid[SUP] 2 [/SUP], Jonathan J Stone[SUP] 3 [/SUP], Claire E Lyons[SUP] 3 [/SUP], Autumn Berlied[SUP] 3 [/SUP], Joseph Nkolola[SUP] 2 [/SUP], Ninaad Lasrado[SUP] 2 [/SUP], Max Peterson[SUP] 1 [/SUP], Laurent Pessaint[SUP] 1 [/SUP], Christopher Kitajewski[SUP] 1 [/SUP], Jake Yalley-Ogunro[SUP] 1 [/SUP], Maciel Porto[SUP] 1 [/SUP], Rebecca Stone[SUP] 1 [/SUP], Mehtap Cabus[SUP] 1 [/SUP], Daniel Valentin[SUP] 1 [/SUP], Alex Van Ry[SUP] 1 [/SUP], Brandon Narvaez[SUP] 1 [/SUP], Tatyana Orekov[SUP] 1 [/SUP], Swagata Kar[SUP] 1 [/SUP], Elyse Teow[SUP] 1 [/SUP], Katelyn Kouneski[SUP] 1 [/SUP], Abismel Ferreira[SUP] 1 [/SUP], Jason Velasco[SUP] 1 [/SUP], Robert Campbell[SUP] 1 [/SUP], Colin Henderson[SUP] 1 [/SUP], Wilfred Beah[SUP] 1 [/SUP], Grishma Patel[SUP] 1 [/SUP], Brad Finneyfrock[SUP] 1 [/SUP], Anthony Cook[SUP] 1 [/SUP], Soumen Paul[SUP] 1 [/SUP], Joost Haasnoot[SUP] 4 [/SUP], Lisbeth Ramirez-Carvajal[SUP] 4 [/SUP], Martin H Koldijk[SUP] 4 [/SUP], Sagrario Arias Rivas[SUP] 4 [/SUP], Clarissa M Koch[SUP] 4 [/SUP], Jaap Goudsmit[SUP] 5 [/SUP], Mark G Lewis[SUP] 1 [/SUP], Amanda J Martinot[SUP] 3 [/SUP], Dan H Barouch[SUP] 6 [/SUP]
Affiliations
- PMID: 40829590
- DOI: 10.1016/j.immuni.2025.07.020
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.
Keywords: H5N1; immunity; influenza; macaque; pathogenesis.