The long-term goal of REVirus Lab is to delineate the molecular determinants of host susceptibility (capacity for virus entry) and permissiveness (capacity for virus replication) of (Re)-Emerging RNA viruses such as hantaviruses and coronaviruses. Carried by a variety of animals, including rodents and bats, these viruses pose significant global public health risk and have a high likelihood of zoonotic spillover. The requirement for biosafety level-3 (BSL-3) containment and lack of authentic isolates for a majority of these viruses has limited research on them. Surrogate viruses such as recombinant vesicular stomatitis viruses (rVSVs) pseudotyped with heterologous entry glycoproteins provide excellent tools for investigating virus entry and virus-host interactions at BSL-2. We have used such rVSVs to discover protocadherin-1 (PCDH1) as a novel receptor for the entry of New World hantaviruses. REVirus Lab will utilize and build upon these tools and methods to define the molecular mechanisms of virus entry and to better understand the antiviral immune responses. This knowledge can eventually be harnessed to develop prophylactic and therapeutic interventions against these viruses, whose spillover is predicted to increase due to climate change and increased overlap of human and reservoir species.