Influenza and PRRS, what do respiratory viruses do when they meet?

Influenza and PRRS, what do respiratory viruses do when they meet?

With the COVID-19 crisis, the question of viral co-infections has become a major issue. What do respiratory viruses do when they meet and what are the consequences for the animal host? The analysis of the consequences of the encounter of swine influenza viruses (Influenza A virus - IAV) with the porcine respiratory dysgenesis syndrome virus (vSDRP), a virus from a viral family (Arteriviridae), which is fairly close to that of the coronaviruses, is a relevant model for understanding these coinfections. The pig is in fact not only a species of major agronomic interest but also a model for humans. The viral interference is strong between these viruses whatever the cell type considered. Remarkably, the epithelial cell, the preferred target of the influenza virus, will react very differently to the influenza virus if it has been pre-exposed to vSDRP. Indeed, it becomes almost resistant to infection by the IAV at various levels. This observation, valid for both wild and vaccine viruses, is a key step in understanding the course of polyinfections and may have important implications for vaccine strategies.

Context

In pig farming, respiratory diseases are responsible for significant economic losses [1]. These disorders are frequently due to a combination of bacterial and viral agents and are then grouped together under the name of "Porcine Respiratory Complex" (PRC) [2]. Among the pathogens involved, porcine respiratory disease syndrome virus (PRDSV) and porcine influenza A viruses (IAV) are considered major players [3-7]. While data on the pathophysiology of PRRS and IAV mono-infections are abundant, co-infection with these two viruses has been little studied [1]. PRRS infection is a persistent infection lasting several weeks due to the ability of the virus to alter the antiviral immune response [6], whereas infection with influenza virus is typically an acute infection.

Results

The results show that vSDRP is able to interfere with IAV infection and alter the cellular antiviral response without infecting IAV target epithelial cells. This effect of vSDRP appears to be less important when the time between viral inoculations is increased. The results were obtained both in vitro and by growing lung explants closer to the reality of the porcine host. Furthermore, preliminary results from our colleagues at ANSES show that what was observed in vitro and ex vivo in our study is transposable in vivo. Our study shows for the first time that a cell apparently of lesser importance in the infection with vSDRP, the epithelial cell, can be strongly influenced during its interaction with the latter with important consequences on its natural infection by influenza viruses.

Perspectives

The research carried out contributes to a better understanding of the porcine respiratory complex and may lead to the development of recommendations for farmers and veterinarians to ensure better control of respiratory diseases in pigs through vaccination. Understanding the variation in the immune response to different pathogens and their multiple combinations also contributes to the optimisation of diagnostic and screening techniques. Furthermore, the identification of all infectious and non-infectious parameters contributing to the aggravation of respiratory diseases allows farmers and veterinarians to reinforce good practices to reduce the dissemination of different pathogens in animal husbandry. We will now continue our research by including Porcine Respiratory Coronavirus (PRCoV) in our viral co-infection experiments. This new virus will be introduced into our experimental protocols with a view to identifying possible phenomena of induced immunity that may occur during co-infections/superinfections between pathogens.

Valorisation

-SAADE G., MENARD D., HERVET C., RENSON P., HUE E., ZHU J., DUBREIL L., PAILLOT R., PRONOST S., BOURRY O., SIMON G., DUPONT J., BERTHO N.*, MEURENS F*. Porcine reproductive and respiratory syndrome virus interferes with swine influenza A virus infection of epithelial cells. Vaccines, *Contributed equally to this work, 2020, in press.

-SAADE G., DEBLANC C., BOUGON J., MAROIS-CREHAN C., FABLET C., AURAY G., BELLOC C., LEBLANC-MARIDOR M., GAGNON C.A., ZHU J., GOTTSCHALK M., SUMMERFIELD A., SIMON G., BERTHO N., MEURENS F. Coinfections and their molecular consequences in the porcine respiratory tract. Veterinary Research, 2020, in press.

 

Bibliographic references

1.            Saade, G.; Deblanc, C.; Bougon, J.; Marois-Créhan, C.; Fablet, C.; Auray, G.; Belloc, C.; Leblanc-Maridor, M.; Gagnon, C.A.; Zhu, J.; et al. Coinfections and their molecular consequences in the porcine respiratory tract. Vet. Res. 2020, 51, 80, doi:10.1186/s13567-020-00807-8.

2.            Opriessnig, T.; Giménez-Lirola, L.G.; Halbur, P.G.; Gimenez-Lirola, L.G.; Halbur, P.G.; Giménez-Lirola, L.G.; Halbur, P.G. Polymicrobial respiratory disease in pigs. Animal Health Research Reviews 2011, 12, 133–148, doi:10.1017/S1466252311000120.

3.            Fablet, C.; Marois-Crehan, C.; Simon, G.; Grasland, B.; Jestin, A.; Kobisch, M.; Madec, F.; Rose, N. Infectious agents associated with respiratory diseases in 125 farrow-to-finish pig herds: a cross-sectional study. Vet Microbiol 2012, 157, 152–163.

4.            Fablet, C.; Marois, C.; Dorenlor, V.; Eono, F.; Eveno, E.; Jolly, J.P.; Le Devendec, L.; Kobisch, M.; Madec, F.; Rose, N. Bacterial pathogens associated with lung lesions in slaughter pigs from 125 herds. Res Vet Sci 2012, 93, 627–630.

5.            Choi, Y.K.; Goyal, S.M.; Joo, H.S. Retrospective analysis of etiologic agents associated with respiratory diseases in pigs. Can Vet J 2003, 44, 735–737.

6.            Lunney, J.K.; Fang, Y.; Ladinig, A.; Chen, N.; Li, Y.; Rowland, B.; Renukaradhya, G.J. Porcine Reproductive and Respiratory Syndrome Virus (PRRSV): Pathogenesis and Interaction with the Immune System. Annual Review of Animal Biosciences 2016, 4, 129–154, doi:10.1146/annurev-animal-022114-111025.

7.            Crisci, E.; Mussa, T.; Fraile, L.; Montoya, M. Review: influenza virus in pigs. Mol Immunol 2013, 55, 200–211.

coinfections

Different types of interactions between IAV and vSDRP are possible. 1) IAV and vSDRP can bind to each other outside the cell or, 2) and 4), to the other virus when one of the two viruses has adhered to its target cell. The influenza virus can also interact with its receptor without being influenced by vSDRP

In animal husbandry, respiratory diseases are responsible for significant economic losses [1]. These disorders are frequently due to a combination of bacterial and viral agents and are then grouped together under the name of "Porcine Respiratory Complex" (PRC) [2]. Among the pathogens involved, porcine respiratory disease syndrome virus (PRDSV) and porcine influenza A viruses (IAV) are considered major players [3-7]. While data on the pathophysiology of PRRS and IAV mono-infections are abundant, co-infection with these two viruses has been little studied [1]. PRRS infection is a persistent infection lasting several weeks due to the ability of the virus to alter the antiviral immune response [6], whereas infection with influenza virus is typically an acute infection.