Dataset Information

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

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.

ORGANISM(S): Macaca mulatta Macaca fascicularis

PROVIDER: GSE287709 | GEO | 2025/08/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Occasional transmission of highly pathogenic avian H5N1 influenza viruses to humans causes severe pneumonia with high mortality. To better understand the mechanisms via which H5N1 viruses induce severe disease in humans, we infected cynomolgus macaques with six different H5N1 strains isolated from human patients and compared their pathogenicity and the global host responses to the virus infection. Although all H5N1 viruses replicated in the respiratory tract, there was substantial heterogeneity in their replicative ability and in the disease severity induced, which ranged from asymptomatic to fatal. A comparison of global gene expression between severe and mild disease cases indicated that interferon-induced up-regulation of genes related to innate immunity, apoptosis, and antigen processing/presentation in the early phase of infection was limited in severe disease cases, although interferon expression was up-regulated in both severe and mild cases. Furthermore, co-expression analysis of microarray data, which reveals the dynamics of host responses during the infection, demonstrated that the limited expression of these genes early in infection led to a failure to suppress virus replication and to the hyperinduction of genes related to immunity, inflammation, coagulation, and homeostasis in the late phase of infection, resulting in a more severe disease. Our data suggest that the attenuated interferon-induced activation of innate immunity, apoptosis, and antigen presentation in the early phase of H5N1 virus infection leads to subsequent severe disease outcome. Bronchial brushes for microarray studies were obtained from female cynomolgus macaques infected with influenza viruses. Three animals per group were inoculated with one of three H5N1 influenza viruses (VN3028II, VN30259 or VN3040). The early phase of infection refers to timepoints Pre (prior to infection), 1, and 3 days post-infection. The late phase of infection refers to days 5 and 7 post-infection. Samples collected prior to infection (labeled as Pre) served as control data for each infection group.

Dataset Information

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

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets