Lethal Disease Following H5N1 Avian Influenza Virus Clade 2.3.4.4b Infection in Macaques
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PROVIDER: PRJNA1214282 | ENA |
REPOSITORIES: ENA
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Project description:The H5N1 avian influenza virus clade 2.3.4.4b outbreak represents a major pandemic threat for humans. Although most human cases to date have been mild, several severe cases of respiratory illness have been reported. A key unanswered question is the pathogenesis of H5N1 infection in primates following respiratory infection. In this study, we observed severe clinical disease in cynomolgus and rhesus macaques following respiratory infection with the H5N1 isolate A/Texas/37/2024 (hu-TX37-H5N1). Cynomolgus macaques inoculated with a high dose of hu-TX37-H5N1 developed severe consolidative necrotizing pneumonia with extrapulmonary spread. Clinical disease was rapidly progressive and lethal in 100% (9 of 9) of macaques by day 5-9 following challenge. Rhesus macaques inoculated with varying doses of hu-TX37-H5N1 demonstrated dose-dependent mortality, and surviving animals showed robust natural protective immunity against high dose re-challenge. H5N1 infection in both cynomolgus and rhesus macaques was characterized by upregulation of proinflammatory cytokine, innate immune cell, complement and coagulation, apoptosis, and immune exhaustion pathways and downregulation of NK, T, and B cell activation and differentiation pathways. Taken together, our data demonstrate severe respiratory disease with H5N1 clade 2.3.4.4b in nonhuman primates and suggest that acute inflammation and immune dysregulation are key contributors to disease pathogenesis.
2025-08-01 | GSE287709 | GEO
Project description:Viral pneumonia has been frequently reported during early stages of influenza virus pandemics and in many human cases of highly pathogenic avian influenza (HPAI) H5N1 virus infection. To better understand the pathogenesis of this disease, we produced non-lethal viral pneumonia in rhesus macaques by using an HPAI H5N1 virus (A/Anhui/2/2005; referred to as Anhui/2). Infected macaques were monitored for 14 days, and tissue samples were collected at 6 time points for virologic, histopathologic and transcriptomic analyses.
2012-04-11 | GSE37149 | GEO
Project description:U.S. H5N1 clade 2.3.4.4b genotype B3.13 immediate releases related to emergence and spread in dairy cattle
| PRJNA1102327 | ENA
Project description:Experimental spillover of H5N1 clade 2.3.4.4b high pathogenicity avian influenza virus from gulls to minks reveals mammalian adaptation without spillback potential
| PRJEB95805 | ENA
Project description:Genetic Diversity of Highly Pathogenic Avian Influenza H5N1 Clade 2.3.4.4b Detected in Pennsylvania Poultry During 2022 Disease Outbreak
| PRJNA1223829 | ENA
Project description:Viral pneumonia has been frequently reported during early stages of influenza virus pandemics and in many human cases of highly pathogenic avian influenza (HPAI) H5N1 virus infection. To better understand the pathogenesis of this disease, we produced non-lethal viral pneumonia in rhesus macaques by using an HPAI H5N1 virus (A/Anhui/2/2005; referred to as Anhui/2). Infected macaques were monitored for 14 days, and tissue samples were collected at 6 time points for virologic, histopathologic and transcriptomic analyses. Thirteen colony-bred male or female rhesus macaques (Macaca mulatta), aged from 2.5 to 3.5 years and ranging in weight from 2.8 to 4.4 kg, were used for experiments. Twelve macaques were individually infected intratracheally with 10^7 EID50 of Anhui/2 in 4 ml of phosphate-buffered saline (PBS). At 6 h, 12 h, 1 d, 3 d, 6 d, and 14 d post-infection (p.i.), two animals per time-point were euthanized under anesthesia and necropsies were performed. Lung samples were collected and stored in RNAlater (Ambion, Austin, USA) at -80M-BM-0C for RNA analyses. The remaining macaque (mock-infected) was inoculated with 4 ml of PBS intratracheally and euthanized at 6 h p.i. Lung tissues from the mock-infected animal were collected and stored as described.
2012-04-10 | E-GEOD-37149 | biostudies-arrayexpress
Project description:Over the last decade, more than half of humans infected with highly pathogenic avian influenza (HPAI) H5N1 viruses have died, and yet virus-induced host signaling has yet to be clearly elucidated. Airway epithelia are known to produce inflammatory mediators that contribute to HPAI H5N1-mediated pathogenicity, but a comprehensive analysis of the host response in this cell type is lacking. Here, we leveraged a systems biology method called weighted gene correlation network analysis (WGCNA) to identify and statistically validate signaling sub-networks that define the dynamic transcriptional response of human bronchial epithelial cells after infection with influenza A/Vietnam/1203/2004 (H5N1, VN1203). A detailed examination of two sub-networks involved in the immune response and keratin filament formation revealed potential novel mediators of HPAI H5N1 pathogenesis, and additional experiments validated upregulation of these transcripts in response to VN1203 infection in C57BL/6 mice. Using emergent network properties, we provide fresh insight into the host response to HPAI H5N1 virus infection, and identify novel avenues for perturbation studies and potential therapeutic intervention of fatal HPAI H5N1 disease.
2011-09-02 | GSE28166 | GEO
Project description:This study is planned to characterize the proteome profile of HPAI H5N1 virus infected chicken lung tissues to identify the molecular pathogenesis and proteomic determinant associate with disease progression in susceptible host.
2022-03-02 | PXD010358 | Pride
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.
2014-05-27 | E-GEOD-57970 | biostudies-arrayexpress