Contribution of host immune responses against influenza d virus infection toward secondary bacterial infection in a mouse model

Raegan M. Skelton, Kelly M. Shepardson, Alexis Hatton, Patrick T. Wilson, Chithra Sreenivasan, Jieshi Yu, Dan Wang, Victor C. Huber, Agnieszka Rynda-Apple

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Influenza D viruses (IDV) are known to co-circulate with viral and bacterial pathogens in cattle and other ruminants. Currently, there is limited knowledge regarding host responses to IDV infection and whether IDV infection affects host susceptibility to secondary bacterial infections. To begin to address this gap in knowledge, the current study utilized a combination of in vivo and in vitro approaches to evaluate host cellular responses against primary IDV infection and secondary bacterial infection with Staphylococcus aureus (S. aureus). Primary IDV infection in mice did not result in clinical signs of disease and it did not enhance the susceptibility to secondary S. aureus infection. Rather, IDV infection appeared to protect mice from the usual clinical features of secondary bacterial infection, as demonstrated by improved weight loss, survival, and recovery when compared to S. aureus infection alone. We found a notable increase in IFN-β expression following IDV infection while utilizing human alveolar epithelial A549 cells to analyze early anti-viral responses to IDV infection. These results demonstrate for the first time that IDV infection does not increase the susceptibility to secondary bacterial infection with S. aureus, with evidence that anti-viral immune responses during IDV infection might protect the host against these potentially deadly outcomes.

Original languageEnglish
Article number994
Issue number11
StatePublished - Oct 29 2019

Bibliographical note

Funding Information:
Funding: This research was funded by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences (NIGMS) of the NIH (P20GM103443, V.H.), with additional support from the Division of Basic Biomedical Sciences at USD (V.H.), the Sanford School of Medicine Medical Research Committee (P.W.), the U. Discover program at USD (P.W.), a grant from the National Science Foundation (DGE-1633213) (R.S.), National Institute of General Medical Sciences (NIGMS) of the NIH (P20GM103474, A.H., A.R-A.), National Institute of Allergy and Infectious Disease (NIAID) of the NIH (R01AI04905, K.S., A.R-A.), and the MSU Agricultural Experiment Station (A.R-A.). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

Publisher Copyright:
© 2019 by the authors.


  • Influenza D virus
  • Interferon
  • Macrophages
  • Secondary bacterial infection

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology


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