TIM-1 Serves as a Nonredundant Receptor for Ebola Virus, Enhancing Viremia and Pathogenesis

Bethany Brunton; Kai Rogers; Elisabeth K. Phillips; Rachel B. Brouillette; Ruayda Bouls; Noah S. Butler; Wendy Maury

In contrast to our EBOV GP/rVSV findings, we observed no difference in the survival curve 289 between the two strains of mice (Fig. 1C ). Since it is likely that VSV bearing it native GP is 290 more pathogenic than a recombinant VSV containing a different viral GP, we also evaluated 291 mortality associated with different doses of VSV and found that administration of as little as 10 1 292 iu of VSV was lethal to Ifnar -/mice (Supplemental Fig. 2 ). Thus, we repeated VSV infections in 293 control and TIM-1 -/mice at a challenge dose of 10 1 iu to determine if subtle changes in virus 294 pathogenesis could be discerned. Even at this low dose, there was no difference in the survival in 295 the TIM-1 -/mice versus the control mice (Fig. 1D ). These results provide evidence that the 296 difference in EBOV GP/rVSV pathogenesis in BALB/c Ifnar -/and TIM-1 -/mice was due to the 297 presence of EBOV GP expressed in the recombinant VSV rather than other VSV genes. The 298 reduced pathogenesis of EBOV GP expressing virus in TIM-1 -/mice was consistent with 299 findings described by Younan et al. using maEBOV [34] . 300 301