Evidence for Co-evolution of West Nile Virus and House Sparrows in North America

West Nile virus (WNV) has been maintained in North America in enzootic cycles between mosquitoes and birds since it was first described in North America in 1999. House sparrows (HOSPs; Passer domesticus) are a highly competent host for WNV that have contributed to the rapid spread of WNV across the U.S.; however, their competence has been evaluated primarily using an early WNV strain (NY99) that is no longer circulating. Herein, we report that the competence of wild HOSPs for the NY99 strain has decreased significantly over time, suggesting that HOSPs may have developed resistance to this early WNV strain. Moreover, recently isolated WNV strains generate higher peak viremias and mortality in contemporary HOSPs compared to NY99. These data indicate that opposing selective pressures in both the virus and avian host have resulted in a net increase in the level of host competence of North American HOSPs for currently circulating WNV strains.Author Summary: West Nile virus (WNV) emerged in North America in 1999 and rapidly spread across the U.S. due to the presence of highly susceptible mosquito vectors and avian hosts. One of the major avian reservoirs for WNV in the U.S. is the house sparrow (HOSP), which has low mortality during WNV infection. Here, we investigate how the response of wild HOSPs to WNV infection has changed as a result of the 15-year history of WNV circulation in the U.S. In addition, we evaluated the impact of WNV evolution on viral infection in HOSPs and report that WNV has become increasingly pathogenic to HOSPs over time, while HOSPs may have developed resistance to early WNV strains. Thus, HOSPs are still likely to be an important avian reservoir for WNV in the U.S., and WNV has adapted to its avian hosts during emergence in North America.