Avian Influenza A Virus Infects Swine Airway Epithelial Cells without Prior Adaptation

Abstract

Pigs play an important role in the interspecies transmission of influenza A viruses (IAV). The porcine airway epithelium contains binding sites for both swine/human IAV (α2,6-linked sialic acids) and avian IAV (α2,3-linked sialic acids) and therefore is suited for adaptation of viruses from other species as suggested by the “mixing vessel theory”. Here, we applied well-differentiated swine airway epithelial cells to find out whether efficient infection by avian IAV requires prior adaption. Furthermore, we analyzed the influence of the sialic acid-binding activity and the virus-induced detrimental effects. Surprisingly, an avian IAV H1N1 strain circulating in European poultry and waterfowl shows increased and prolonged viral replication without inducing a strong innate immune response. This virus could infect the lower respiratory tract in our precision cut-lung slice model. Pretreating the cells with poly (I:C) and/or JAK/STAT pathway inhibitors revealed that the interferon-stimulated innate immune response influences the replication of avian IAV in swine airway epitheliums but not that of swine IAV. Further studies indicated that in the infection by IAVs, the binding affinity of sialic acid is not the sole factor affecting the virus infectivity for swine or human airway epithelial cells, whereas it may be crucial in well-differentiated ferret tracheal epithelial cells. Taken together, our results suggest that the role of pigs being the vessel of interspecies transmission should be reconsidered, and the potential of avian H1N1 viruses to infect mammals needs to be characterized in more detail.

Potency of an Inactivated Influenza Vaccine against a Challenge with A/Swine/Missouri/A01727926/2015 (H4N6) in Mice for Pandemic Preparedness

“…An influenza pandemic is derived from influenza viruses circulating among pigs. Pigs are infected with both human or avian viruses [ 22 ], causing a reassortment between two types of viruses and thereby producing pandemic candidates with an antigenic shift. Because the antigenicity is conserved in waterfowl, which are natural hosts of influenza viruses [ 23 ], monitoring the viruses circulating in waterfowl to prepare for an influenza pandemic in humans via pigs is necessary.…”

The Cell Tropism of Porcine Respiratory Coronavirus for Airway Epithelial Cells Is Determined by the Expression of Porcine Aminopeptidase N

“…Primary porcine tracheal epithelial cells (PTECs) and primary porcine bronchial epithelial cells (PBECs) were harvested from the 5-month-old pigs’ trachea and bronchial, respectively, as previously described [ 19 , 20 ]. Briefly, PTECs and PBECs firstly maintained in bronchial epithelial cell growth medium (Lonza, Basel, Switzerland).…”

“…To determine the infectivity of the harvested supernatants, a focus-forming assay was performed as described previously with some modifications [ 19 ]. Briefly, ST cells were seeded in 96-well plates one day before the experiment.…”

Adenoviral Vectors as Vaccines for Emerging Avian Influenza Viruses

“…Human and classical swine IAVs preferentially bind to α2,6 linked SAs, while avian IAVs preferentially bind to α2,3 linked SAs. SA receptors are mostly found on epithelial cells, with α2,3 linked SAs found in the intestines and respiratory tract of birds (and the lower respiratory tract of humans) ( 13 ), while α2,6 linked SAs are mostly found in the respiratory tract of humans and pigs ( 2 , 12 , 14 – 16 ). Intermediary hosts, such as pigs, play a role in the adaptation of IAVs by acting as a “mixing vessel” and facilitating reassortment, as expression of both α2,3 and α2,6 linked SAs enables them to be simultaneously infected by both human and avian influenza viruses ( 17 ) ( Figure 2 ).…”

“…tract of birds (and the lower respiratory tract of humans) (13), while a2,6 linked SAs are mostly found in the respiratory tract of humans and pigs (2,12,(14)(15)(16). Intermediary hosts, such as pigs, play a role in the adaptation of IAVs by acting as a "mixing vessel" and facilitating reassortment, as expression of both a2,3 and a2,6 linked SAs enables them to be simultaneously infected by both human and avian influenza viruses (17) (Figure 2).…”