Background: Cache Valley virus (CVV) is an understudied Orthobunyavirus with a high spillover transmission potential due to its wide geographical distribution and large number of associated hosts and vectors. Although CVV is known to be widely distributed throughout North America, no studies have explored its geography or employed computa- tional methods to explore the mammal and mosquito species likely participating in the CVV sylvatic cycle.

Methods: We used a literature review and online databases to compile locality data for CVV and its potential vectors and hosts. We linked location data points with climatic data via ecological niche modeling to estimate the geographi- cal range of CVV and hotspots of transmission risk. We used background similarity tests to identify likely CVV mosquito vectors and mammal hosts to detect ecological signals from CVV sylvatic transmission.

Results: CVV distribution maps revealed a widespread potential viral occurrence throughout North America. Ecologi- cal niche models identified areas with climate, vectors, and hosts suitable to maintain CVV transmission. Our back- ground similarity tests identified Aedes vexans, Culiseta inornata, and Culex tarsalis as the most likely vectors and Odoc- oileus virginianus (white-tailed deer) as the most likely host sustaining sylvatic transmission.

Conclusions: CVV has a continental-level, widespread transmission potential. Large areas of North America have suit- able climate, vectors, and hosts for CVV emergence, establishment, and spread. We identified geographical hotspots that have no confirmed CVV reports to date and, in view of CVV misdiagnosis or underreporting, can guide future surveillance to specific localities and species.