# Influenza D virus
**Influenza D virus** (IDV) is an influenza virus of the family [Orthomyxoviridae](https://www.edgepedia.org/orthomyxoviridae), genus *Deltainfluenzavirus*, first isolated in 2011 from a pig with respiratory disease in Oklahoma, United States, and now recognized as a respiratory pathogen whose primary reservoir is cattle.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/) • [2](https://pmc.ncbi.nlm.nih.gov/articles/PMC8279278/) It is the fourth influenza type after influenza A, B, and C, and the only one that mainly affects cattle, with frequent spillover to swine and other mammals.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/)
| Key fact | Detail |
|---|---|
| Discovery | First isolated in 2011 from a clinically ill pig in Oklahoma, USA; antibodies were found in 9.5% of surveyed US swine[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/) |
| Taxonomy | Classified by the International Committee on Taxonomy of Viruses in August 2016 as a new genus, *Deltainfluenzavirus*, species Influenza D virus, family Orthomyxoviridae[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC8279278/) |
| Genome | Seven negative-sense RNA segments; a single major surface glycoprotein, hemagglutinin-esterase-fusion (HEF), performing receptor binding, receptor destruction, and fusion[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/) |
| Relationship to influenza C | About 50% amino acid identity with influenza C virus overall, a divergence comparable to that between influenza A and B viruses[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/) • [3](https://www.tandfonline.com/doi/pdf/10.1080/21505594.2017.1365216) |
| Primary host | Cattle, where infection is associated with mild respiratory disease and the bovine respiratory disease complex; seroprevalence of 16–96% reported in most of the world[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/) • [4](https://www.cfsph.iastate.edu/Factsheets/pdfs/influenzaD.pdf) |
| Lineages | Two principal lineages, D/OK and D/660, plus the more recent D/Yama2016 and D/Yama2019 lineages in Japan[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/) |
| Human exposure | Seroprevalence of about 1.3% in the general population, but 97% (34/35) among Florida cattle workers; no viable virus has been isolated from a human[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/) • [5](https://wwwnc.cdc.gov/eid/article/32/1/25-1764_article) |
## Discovery and classification
The virus was initially isolated as an influenza C-like virus from pigs with respiratory illness in Oklahoma in 2011.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/) Serological and epidemiological work then showed the virus was more prevalent in cattle than in swine in the United States, and it was proposed as a new genus of the Orthomyxoviridae. The [International Committee on Taxonomy of Viruses](https://www.edgepedia.org/international-committee-on-taxonomy-of-viruses) formalized this in August 2016, creating the genus *Deltainfluenzavirus* with the single species Influenza D virus.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC8279278/) Antibodies against IDV have since been detected in archived US cattle sera dating back at least to 2004, indicating the virus circulated before its discovery.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/)
## Biology
Like influenza C virus, IDV has a genome of seven negative-sense RNA segments and a single major surface glycoprotein, the hemagglutinin-esterase-fusion (HEF) protein, which carries out all entry functions: receptor binding, receptor destroying, and membrane fusion.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/) Influenza A and B viruses, by contrast, have eight segments and two surface glycoproteins. IDV uses 9-O-acetylated sialic acids as cell receptors and binds both the human form (Neu5,9Ac2) and the non-human form (Neu5Gc9Ac) efficiently, which may explain its broad host range compared with influenza C virus, which preferentially binds the human form.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/)
IDV is the most acid-stable of the four influenza types: after treatment at pH 3.0 for 30 minutes it retains approximately 80% of its original infectivity, while influenza A, B, and C viruses are completely inactivated under the same condition. [Reverse genetics](https://www.edgepedia.org/reverse-genetics) experiments identify the HEF protein as the primary determinant of this acid and thermal stability.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/) In cell culture, IDV replicates without restriction at 37 °C and shows broad cell tropism, whereas influenza C virus is limited at that temperature.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/)
## Epidemiology and host range
Cattle serve as the primary reservoir and amplification host, with periodic spillover to other species.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/) IDV has been detected in cattle and swine in North America, Europe, and Asia, and antibodies have been found in sheep, goats, horses, camelids, and wild boars.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/) Studies report cattle seroprevalence of 16–96% in most of the world, with lower rates of 3–21% in East and [West Africa](https://www.edgepedia.org/west-africa); other livestock are less often seropositive, including under 0.5% to 12% of domestic pigs and 1–9% of small ruminants in European and North American studies.[4](https://www.cfsph.iastate.edu/Factsheets/pdfs/influenzaD.pdf)
In cattle, IDV infection causes mild respiratory disease and has been indicated as a causative agent of the bovine respiratory disease complex, the most common and costly disease affecting the global cattle industry.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC8279278/) Experimental infections show that IDV replicates throughout the upper and lower respiratory tract of calves and can alter the structural integrity of the respiratory epithelium.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/)
Since 2011, IDV has diversified into four lineages: D/OK (D/swine/Oklahoma/1334/2011), D/660 (D/bovine/Oklahoma/660/2013), and the Japanese D/Yama2016 and D/Yama2019 lineages, with about 4% diversity in the HEF gene.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/) The virus evolves with a high substitution rate for the HEF gene, 1.68 × 10−3 nucleotide substitutions per site per year, about three times faster than influenza C virus HEF and comparable to some influenza A and B subtypes.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/)
## Zoonotic potential
Evidence that IDV infects humans comes mainly from serology, since no viable, infectious IDV has been isolated from a human.[5](https://wwwnc.cdc.gov/eid/article/32/1/25-1764_article) Three independent serological studies define the picture. A cohort aged 60 years and older in Canada and the eastern United States showed a seroprevalence of about 1.3% (4/312). A cross-sectional study of Florida adults found 97% seroprevalence (34/35) among cattle workers by microneutralization assay, mirroring seroprevalence in the cattle population, against 18% (2/11) in non-cattle-exposed persons.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/) A longitudinal study of more than 1,000 serum samples collected in Italy from 2005 to 2017 found antibody prevalence rising over the period, with 33.9–41.0% of subjects positive in some years, temporally correlated with epidemics in Italian pigs.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/)
**Direct evidence of exposure.** IDV genome has been detected in the nasal wash of a swine farm worker in Southeast Asia, in bioaerosol samples at Raleigh Durham International Airport, and in hospital visitors in North Carolina.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/) In a five-day study of 31 workers on five large US dairy farms, IDV was found in the nasal washes of 67% of participants at least once.[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC10748149/) Whether IDV causes disease in humans remains unknown; available studies suggest infections are largely subclinical, especially among people with occupational animal exposure.[5](https://wwwnc.cdc.gov/eid/article/32/1/25-1764_article)
Laboratory work supports susceptibility. IDV replicates efficiently in human lung epithelial cell lines, primary well-differentiated airway epithelial cultures, and precision-cut lung slices, reaching titers comparable to human influenza A virus, and most isolates tested elicited a muted innate immune response rather than the hyperinflammation seen with pandemic strains.[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC12889682/) IDV also replicates and transmits in ferrets, a surrogate model for human influenza studies.[5](https://wwwnc.cdc.gov/eid/article/32/1/25-1764_article) One caution in interpreting serology is that IDV and influenza C virus share about 50% homology in the HEF protein, the primary target of the assays, so the precise nature of human infection may require virus-specific antibody tests.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/)
## Prevention in animals
No specific vaccines or treatments for influenza D in animals are commercially established. Candidate vaccines include a chemically inactivated whole-virus vaccine that gave calves partial protection against homologous challenge, and a DNA vaccine expressing a consensus HEF gene that protected guinea pigs completely against challenge with representatives of the D/OK and D/660 lineages.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/) Because infections are common even in asymptomatic animals, there do not appear to be practical, cost-effective measures to exclude these viruses from herds.[4](https://www.cfsph.iastate.edu/Factsheets/pdfs/influenzaD.pdf)
## References
1. [Liu R, Sheng Z, Huang C, Wang D, Li F (2020). Influenza D Virus. Current Opinion in Virology / PMC.](https://pmc.ncbi.nlm.nih.gov/articles/PMC7755673/)
2. [The first decade of research advances in influenza D virus. PMC.](https://pmc.ncbi.nlm.nih.gov/articles/PMC8279278/)
3. [Novel Influenza D virus: Epidemiology, pathology, evolution and biological characteristics. Virulence (2017).](https://www.tandfonline.com/doi/pdf/10.1080/21505594.2017.1365216)
4. [Influenza D factsheet, Center for Food Security and Public Health, Iowa State University.](https://www.cfsph.iastate.edu/Factsheets/pdfs/influenzaD.pdf)
5. [Emerging Respiratory Virus Threats from Influenza D and Canine Coronavirus HuPn-2018, Emerging Infectious Diseases (2026).](https://wwwnc.cdc.gov/eid/article/32/1/25-1764_article)
6. [Influenza D in Domestic and Wild Animals. PMC.](https://pmc.ncbi.nlm.nih.gov/articles/PMC10748149/)
7. [Efficient replication of influenza D virus in the human airway underscores zoonotic potential. PMC.](https://pmc.ncbi.nlm.nih.gov/articles/PMC12889682/)
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*Topic: Encyclopedia › Life and health › Microorganisms and fungi › Viruses and acellular agents › Viruses of animals and humans › Influenza viruses › Influenza D*
*Initially written Sep 17, 2026 · Reviewed: Oct 21, 2026 · Edited: Oct 15, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*
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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license