Disruption of influenza A virus transmission in gene-edited pigs.

Influenza A virus (IAV) infection in pigs causes significant economic losses in the swine industry. More importantly, pigs serve as an intermediate host for generating reassortant viruses with pandemic potential. Previously, gene-edited pigs lacking the TMPRSS2 gene were generated and tested for susceptibility to IAV infection. Experimental infection of TMPRSS2 knockout pigs (TMPRSS2 KO pigs) resulted in limited nasal shedding, posing the question about their ability to transmit IAV. Therefore, this study evaluated IAV transmission from principal-infected (donor) TMPRSS2 KO pigs to sentinel (recipient) TMPRSS2 KO and wild-type (WT) pigs. As expected, limited amounts of infectious virus were shed via the nasal cavity by the principal-infected KO pigs. After co-housing with principal-infected KO pigs at 2 days post-challenge, sentinel KO pigs remained uninfected until the end of observation period of 21 days as shown by the absence of infectious virus and seroconversion. In addition, there was significantly delayed transmission of IAV from principal-infected KO pigs to sentinel WT pigs when compared to WT-to-WT transmission. These results support a significant impairment of IAV transmission in TMPRSS2 KO pigs.