Arboviruses such as yellow fever virus (YFV) are transmitted between arthropod 
vectors and vertebrate hosts. While barriers limiting arbovirus population 
diversity have been observed in mosquitoes, whether barriers exist in vertebrate 
hosts is unclear. To investigate whether arboviruses encounter bottlenecks 
during dissemination in the vertebrate host, we infected immunocompetent mice 
and immune-deficient mice lacking alpha/beta interferon (IFN-α/β) receptors 
(IFNAR⁻/⁻ mice) with a pool of genetically marked viruses to evaluate 
dissemination and host barriers. We used the live attenuated vaccine strain 
YFV-17D, which contains many mutations compared with virulent YFV. We found that 
intramuscularly injected immunocompetent mice did not develop disease and that 
viral dissemination was restricted. Conversely, 32% of intramuscularly injected 
IFNAR⁻/⁻ mice developed disease. By following the genetically marked viruses 
over time, we found broad dissemination in IFNAR⁻/⁻ mice followed by clearance. 
The patterns of viral dissemination were similar in mice that developed disease 
and mice that did not develop disease. Unlike our previous results with 
poliovirus, these results suggest that YFV-17D encounters no major barriers 
during dissemination within a vertebrate host in the absence of the type I IFN 
response.