Efficient #replication of #influenza D virus in the #human #airway underscores zoonotic potential

 

Abstract

Influenza D virus (IDV), primarily found in livestock species, has demonstrated cross-species transmission potential, yet its threat to humans remains poorly understood. Here, we curated a panel of IDV isolates collected during field surveillance from 2011 to 2020 from swine and cattle to assess their ability to infect human airway cells as a proxy for zoonotic threat assessment. Using lung epithelial cell lines, primary well-differentiated airway epithelial cultures, and precision-cut lung slices, we demonstrated that IDV efficiently propagates in cells and tissues from the human respiratory tract, reaching titers comparable to human influenza A virus (IAV). Infection kinetics in primary porcine airway cultures and respiratory tissues mirrored those from human, suggesting similar infectivity across species. To define host responses to IDV infection, we evaluated innate immune sensing and downstream interferon signaling in human respiratory cells. IDV infection resulted in markedly reduced activation of interferon regulatory factor (IRF) signaling and diminished induction of interferon lambda 1 and interferon-stimulated genes compared to IAV, indicating inefficient activation of innate immune sensing pathways. However, IDV replication was potently restricted in interferon-pretreated cells, demonstrating sensitivity to interferon-mediated antiviral effector mechanisms once an antiviral state was established. Together, these findings show that IDV can efficiently infect the human airway while limiting innate immune sensing, a feature that may facilitate zoonotic spillover. Our study highlights the need for enhanced surveillance of IDV at the animal-human interface and provides a foundation for further investigation into its biology and potential for causing human infection and disease.

Competing Interest Statement

The author E.M.K. is currently employed by AbbVie Inc. The author was not affiliated with AbbVie Inc at the time of experiment design, data acquisition, or analysis.

Funder Information Declared

United States Department of Agriculture (USDA) National Institute of Food and Agriculture (NIFA), 2025-39601-44639

The Enterprise for Research, Innovation, and Knowledge at The Ohio State University

Centers of Excellence for Influenza Research and Response, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Department of Health and Human Services, HHSN272201400006C, 75N93021C00016

National Institutes of Health, T35 5T35OD010977

National Institutes of Health, P30 CA016058

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.02.07.704474v1

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Emerging Respiratory #Virus #Threats from #Influenza D and Canine #Coronavirus HuPn-2018

 

Abstract

In 2009 and again in 2019, public health warnings were confirmed by the emergence, rapid widespread transmission, and lethality of novel influenza and coronaviruses. The world continues to suffer disease from these respiratory viruses. Two newly recognized emergent respiratory viruses, influenza D and canine coronavirus HuPn-2018, have been shown to have considerable potential for causing future human epidemics, but diagnostics and surveillance for the viruses are lacking. We reviewed data regarding influenza D virus and coronavirus canine coronavirus HuPn-2018. Those data strongly indicate that these viruses are major newly recognized threats. However, little is being done to respond to or prevent disease associated with these viruses, warranting the question of whether we will learn from previous pandemics.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/1/25-1764_article

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#Influenza D Virus in Black #Donkeys, Northern #China

 

Abstract

Influenza D virus (IDV) is prevalent in cattle in China, and a risk for spillover to other species exists. We detected IDV antibodies in 6/315 of black donkeys in northern China, suggesting cattle-to-donkey transmission and demonstrating the expanding host range of IDV and the need for reassessment of cross-species transmission risks.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/31/12/25-0666_article

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Experimental #infection of #alpacas (Vicugna pacos) with #Influenza C and D viruses results in subclinical upper respiratory tract disease

Abstract

Influenza D virus (IDV), a new genus within the Orthomyxoviridae family, was initially detected in pigs and cattle. IDV is structurally similar to influenza C virus (ICV). Influenza A, C and D viruses all have non-human maintenance hosts and likely circulate in several mammalian species. Camelids, as a reservoir for zoonotic viruses, were not extensively studied until the emergence of the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. Antibody responses to both ICV and IDV could be detected in dromedary camels from Kenya but not differentiated, owing to cross-reactivity. It was unclear whether these findings reflected a technical issue or suggested a role for camelids in ICV and IDV ecology. In the present study, therefore, alpacas (Vicugna pacos), a camelid species, were experimentally inoculated with ICV (C/Victoria/1/2011) or IDV (D/bovine/France/5920/2014) to assess susceptibility and assess the antibody response. We have demonstrated that alpacas can be experimentally infected with both ICV and IDV with subclinical infection of the upper respiratory tract (URT), suggesting that virus transmission could potentially occur. These findings accord with previous serology results obtained for camelids and indicate a putative role for these species in ICV and IDV ecology.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.07.28.667103v1

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#Influenza D Virus in Domestic and Stray #Cats, Northern #China, 2024

Abstract

Influenza D virus infects primarily cattle, but infrequent reports of infections in cats occur. We detected influenza D virus antibodies in 8 of 360 cats in northern China. Domestic cats showed higher susceptibility than strays. Our results suggest a previously overlooked aspect of epidemiology of this virus in companion animals.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/25-0042_article

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High Prevalence of #Influenza D Virus #Infection in #Swine, Northern Ireland

Abstract

We detected influenza D virus in multiple swine herds in Northern Ireland. Whole-genome sequencing showed several circulating genotypes and novel mutations in the receptor-binding site and esterase domains of the hemagglutinin-esterase fusion protein. Transmission routes of influenza D virus to swine remain to be clarified but could be direct or indirect.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/5/24-1948_article

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#Detection and #Phylogenetic Characterization of #Influenza D in Swedish #Cattle

Abstract

Increased evidence suggests that cattle are the primary host of Influenza D virus (IDV) and may contribute to respiratory disease in this species. The aim of this study was to detect and characterise IDV in the Swedish cattle population using archived respiratory samples. This retrospective study comprised a collection of a total 1763 samples collected between 1 January 2021 and 30 June 2024. The samples were screened for IDV and other respiratory pathogens using real-time reverse transcription quantitative PCR (rRT-qPCR). Fifty-one IDV-positive samples were identified, with a mean cycle threshold (Ct) value of 27 (range: 15–37). Individual samples with a Ct value of <30 for IDV RNA were further analysed by deep sequencing. Phylogenetic analysis was performed by the maximum likelihood estimation method on the whole IDV genome sequence from 16 samples. The IDV strains collected in 2021 (n = 7) belonged to the D/OK clade, whereas samples from 2023 (n = 4) and 2024 (n = 5) consisted of reassortants between the D/OK and D/660 clades, for the PB2 gene. This study reports the first detection of IDV in Swedish cattle and the circulation of D/OK and reassortant D/OK-D/660 in this population.

Source: Viruses, https://www.mdpi.com/1999-4915/17/1/17

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