Influenza D and the Dynamic World of Zoonotic Disease Transmission

By: Austin Weynand, MHS

A virus, in its interactions between human and animal, can evolve into a pathogen of enormous infectious potential. The Orthomyxoviridae are notorious for such adaptations, and the most novel of them, influenza D virus (IDV), is currently being investigated by Dr. Jessica Leibler.

To name a few others in the Coronavirus and Orthomyxovirus families: HPAI H5N1, H1N1(pdm09), MERS-CoV, and SARS-CoV-2. Each of these represents a zoonotic spillover event that occurred in the last few decades, and each of them caused an outbreak – the scale of which, of course, varying widely. The implicated animal for H5N1 avian flu infections in humans was birds; for the 2009 H1N1 swine flu pandemic, it was pigs; for MERS in 2012, camels; for SARS-CoV-2, bats (though the immediate species that infected humans is still being investigated).1

Dr. Jessica Leibler, an Assistant Professor at the Boston University School of Public Health and environmental epidemiologist, is acutely aware of such momentous events. She studies IDV, which was first isolated and characterized in 2011. The virus appears to find its natural reservoir in domestic cattle and pigs, and studies published in the last ten years revealed high seroprevalence in the US and abroad (one study from Luxembourg reported up to 80% prevalence in cattle).2-5 In a 2016 pilot study, Professor Gregory Gray (now with UTMB) and his team identified a seroprevalence of IDV in Florida cattle workers of greater than 90%.6

Her current project, however, delved deeper into the course and presentation of IDV in humans. This study, recently published in Zoonoses and Public Health and nested within a larger cohort of American cattle workers, sampled 30 workers across five dairy facilities in two states.7 Each participant provided nasal swabs twice daily over the course of five days, and wore personal breathing-zone air samplers to identify potential active transmission of the pathogen. Dr. Leibler and her collaborators found that about 2/3rds of workers had molecular evidence of IDV in their nasal washes. Hence, nasal carriage of the virus appears to be chronic, yet also “intermittent and transient”. As serological assessments were not performed, IDV infection cannot be established from study data. Dr. Leibler also related that linking nasal carriage of IDV with clinical symptoms and person-to-person spread could not be assessed with the study data. She believes the pathogen is simply poorly-suited to replicate within the human respiratory tract but believes more research needs to be performed in assessing IDV as a human pathogen. She shares that we need to keep a watchful eye on IDV in case it causes future human disease outbreaks.

Depiction of influenza D virus from the National Institutes of Health 

“The more human exposure, the greater the risk that the virus will develop the ability to infect people and be transmissible among them,” she explains. This is the primary focus of such studies. Domestic animals are of particular concern because of their frequent contact with people, thus scrutiny is warranted when evidence of a new pathogen arises in serology. When a viral genetic shift occurs and perfuses into the populous, the consequences can be disastrous; the ongoing COVID-19 pandemic is a living example of this. 

Dr. Leibler is optimistic about the future of viral spillover surveillance. The public awareness of SARS-CoV-2 and the professional consensus on the pandemic’s severity should lead to increased funding and support towards such studies. 

She does lament some obstacles in her field, particularly pertaining to the American food industry. She notes that while corporations and their workforces can be willing to participate in disease studies, their support is often inconsistent. There is concern for their products’ image and loss of public confidence, particularly when a new pathogen is positively identified within their environment. But the importance of surveillance must not be understated – the consequences of neglect are too great. In the last two years, the world has borne witness to this. 

As to the future of this study, Dr. Leibler has several aims. She hopes to further characterize risk factors for IDV infection and continue to monitor for health effects. Catering to genetic epidemiology, she would like to characterize the IDV isolates from this study and compare their phylogeny to IDV samples from other regions. Lastly, and perhaps the most challenging, is to develop evidence-based strategies to prevent viral spread amongst workers and engage the industry

  1. Asha, K., & Kumar, B. (2019). Emerging Influenza D Virus Threat: What We Know so Far! Journal of Clinical Medicine, 8(2), 192. https://doi.org/10.3390/jcm8020192 

  2. Chantal J.S., Justine O., Maude P., Serge L., Félix W., Claude P.M., Judith M.H., Mariette F.D. Influenza D Virus Circulation in Cattle and Swine, Luxembourg, 2012–2016. Emerg. Infect. Dis. J. 2018;24:1388. doi: 10.3201/eid2407.171937 

  3. Hause BM, Ducatez M, Collin EA, Ran, Liu R, Sheng Z, Armien A, Kaplan B, Chakravarty S, Hoppe AD, et al.: Isolation of a novel swine influenza virus from Oklahoma in 2011 which is distantly related to human influenza C viruses. PLoS Pathog 2013, 9:e1003176.  

  4. Chiara C, Silvia F, Aurora De M, Laura B, Ilaria B, Carlo R, Arrigo N, Emanuela F: Detection of Influenza D Virus among Swine and Cattle, Italy. Emerging Infectious Disease journal 2016, 22:352. 

  5. Ducatez MF, Pelletier C, Meyer G: Influenza D Virus in Cattle, France, 2011–2014. Emerging Infectious Diseases 2015, 21:368–371. 

  6. White, S. K., Ma, W., McDaniel, C. J., Gray, G. C., & Lednicky, J. A. (2016). Serologic evidence of exposure to influenza D virus among persons with occupational contact with cattle. Journal of Clinical Virology: The Official Publication of the Pan American Society for Clinical Virology, 81, 31–33. https://doi.org/10.1016/j.jcv.2016.05.017

  7. Leibler JH, Abdelgadir A, Seidel J, White RF, Johnson WE, Reynolds SJ, Gray GC, Schaeffer JW (2022). Influenza D virus exposure among US cattle workers: A call for surveillance. Zoonoses and Public Health 2022;00:1-5. Doi: 10.1111/zph.13008 

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