Senecavirus A (SVA) is an emerging picornavirus of swine that causes foot-and-mouth- (FMD)-like vesicular disease (VD) in affected animals and is known to establish persistent infections in pigs. Most importantly, carrier animals can serve as source of infection to other susceptible pigs. Currently, however, little is known about the mechanisms underlying SVA persistence. Our preliminary data suggests that extensive modulation of host cell survival and antiviral pathways is at play during SVA persistence in swine cells.

We hypothesize that modulation of host survival and antiviral pathways by SVA determines the fate of the infected cell, which cycle between lytic and persistent infection. Here, we propose to dissect the mechanisms underlying SVA persistence using in vivo and in vitro and model systems of persistent infection. The objectives of this study are: (1) To define virus-host cell interactions underlying establishment and maintenance of persistent SVA infection in vivo. (2) To characterize molecular determinants of SVA persistence.

 The work proposed here will significantly contribute to the improvement and sustainability of the US livestock industry by generating foundational knowledge regarding SVA persistence in swine. Such knowledge may be translated to safe live attenuated SVA vaccines and to improved strategies for prevention and control of SVA and other highly relevant VDs of swine.