哈佛医学院Dan H. Barouch团队在研究中取得进展。他们提出了致死性H5N1禽流感病毒分支2.3.4.4b在猕猴感染的免疫发病机制。该项研究成果发表在2025年8月18日出版的《免疫学》上。

本研究探讨了猕猴和恒河猴感染H5N1分离物A/Texas/37/2024 （huTX37-H5N1）后发生严重H5N1疾病的发病机制。食蟹猴在感染后7天发生严重肺炎，死亡率100%。相比之下，恒河猴表现出剂量依赖性死亡率，存活的动物表现出对高剂量再次攻击的保护性免疫。多组学分析表明，H5N1感染的特征是促炎细胞因子、先天免疫细胞、补体、凝血、凋亡和免疫衰竭途径的明显诱导。综上所述，他们的数据表明炎症和免疫失调是H5N1在非人灵长类动物中发病的关键机制。

据了解，H5N1禽流感病毒分支2.3.4.4b的暴发对人类构成了重大的大流行威胁，已报告了一些严重和致命的呼吸道疾病病例。一个关键的未解问题是呼吸道感染后严重H5N1疾病的发病机制。

附：英文原文

Title: Immunopathogenesis of lethal H5N1 avian influenza virus clade 2.3.4.4b infection in macaques

Author: Hanne Andersen, Malika Aid, Jonathan J. Stone, Claire E. Lyons, Autumn Berlied, Joseph Nkolola, Ninaad Lasrado, Max Peterson, Laurent Pessaint, Christopher Kitajewski, Jake Yalley-Ogunro, Maciel Porto, Rebecca Stone, Mehtap Cabus, Daniel Valentin, Alex Van Ry, Brandon Narvaez, Tatyana Orekov, Swagata Kar, Elyse Teow, Katelyn Kouneski, Abismel Ferreira, Jason Velasco, Robert Campbell, Colin Henderson, Wilfred Beah, Grishma Patel, Brad Finneyfrock, Anthony Cook, Soumen Paul, Joost Haasnoot, Lisbeth Ramirez-Carvajal, Martin H. Koldijk, Sagrario Arias Rivas, Clarissa M. Koch, Jaap Goudsmit, Mark G. Lewis, Amanda J. Martinot, Dan H. Barouch

Issue&Volume: 2025-08-18

Abstract: 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.

DOI: 10.1016/j.immuni.2025.07.020

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00329-2