Targeting host sialic acids in the upper respiratory tract with a broadly-acting neuraminidase to inhibit influenza virus transmission

• Published in: bioRxiv
• Main Authors: Ortigoza, Mila B, Mobini, Catherina L, Rocha, Hedy L, Bartlett, Stacey, Loomis, Cynthia A, Weiser, Jeffrey N
• Format: Journal Article
• Language: English
• Published: United States 15.08.2023
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2023.06.02.543524

The ongoing transmission of influenza A viruses (IAV) for the past century continues to be a burden to humans. IAV binds terminal sialic acids (SA) of sugar molecules present within the upper respiratory tract (URT) in order to successfully infect hosts. The two most common SA structures that are important for IAV infection are those with α2,3- and α2,6-linkages. While mice were once considered to be an unsuitable system for studying IAV transmission due to their lack of α2,6-SA in the trachea, we have successfully demonstrated that IAV transmission in infant mice is remarkably efficient. This finding led us to reevaluate the SA composition of the URT of mice using immunofluorescence and examine its contribution to transmission for the first time. We demonstrate that mice express both α2,3- and α2,6-SA in the URT and that the difference in expression between infants and adults contribute to the variable transmission efficiencies observed. Furthermore, selectively blocking α2,3-SA or α2,6-SA within the URT of infant mice using lectins was necessary but insufficient at inhibiting transmission, and simultaneous blockade of both receptors was crucial in achieving the desired inhibitory effect. By employing a broadly-acting neuraminidase (ba-NA) to indiscriminately remove both SA moieties , we effectively suppressed viral shedding and halted the transmission of different strains of influenza viruses. These results emphasize the utility of the infant mouse model for studying IAV transmission, and strongly indicate that broadly targeting host SA is an effective approach that inhibits IAV contagion.