Co-localization of influenza A virus and voltage-dependent calcium channels provides new perspectives on the internalization process in pigs

Abstract

Influenza A virus (IAV) is an RNA virus that causes respiratory disease in a wide range of mammals including humans and pigs. Cav1.2 is a specific voltage-dependent calcium channel (VDCC) important for the internalization of IAV and VDCC inhibitors can decrease IAV disease severity in mice. In this paper, the distribution pattern of a range of VDCCs by immunohistochemistry and Cav1.2 by in situ hybridization in the porcine respiratory tract is documented for the first time. Furthermore, we showed co-localization of VDCC-positive and IAV-positive cells in experimentally infected pigs. These findings provide new perspectives on the IAV internalization process and pave the way for further research investigating the effect of VDDC inhibitors on the IAV infection dynamics in pigs, which could have relevance to humans too.

The avian influenza A virus receptor SA-α2,3-Gal is expressed in the porcine nasal mucosa sustaining the pig as a mixing vessel for new influenza viruses

“…Neu5Gc has previously been shown to act as a decoy receptor ( Takahashi et al., 2014 ) and therefore it is tempting to speculate that the binding of the viruses to this receptor prevented or decreased the infection of the tracheal epithelial cells. Another explanation for the low viral load in the trachea could also be the limited expression of voltage-gated calcium channels (VDCCs) in this tissue since we and others previously have found that VDCCs are important for the internalization process of IAV in pigs ( Kristensen et al., 2023a , Fujioka et al., 2018 ). A novel study described that a high density of high-binding receptors and an additional presence of low-binding receptors increase the viral binding of recombinant human H1N1, H3N2, and avian H5N1 viruses compared to the presence of only a high density of high-binding receptors ( Liu et al., 2022 ).…”