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

The effect of TIM-1 expression on viremia and organ viral loads following i.v. EBOV 304 GP∆O/rVSV infection was examined in serum and organs harvested 1, 3 or 5 days following 305 infection (Fig. 2) . Viremia and infectious virus in various organs were quantified by endpoint 306 dilution titering on Vero cells, a highly permissive cell line for EBOV GP/rVSV. At early times 307 . CC-BY 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/466102 doi: bioRxiv preprint during infection, no difference in viremia or virus load was observed in most organs of TIM-1 308 versus control mice. However, by day 5 of EBOV GPΔO/rVSV infection, TIM-1 -/mice had a 309 100-fold reduction in viremia compared to control mice (Fig. 2) and a similar trend was observed 310 during infections with full length EBOV GP/rVSV (Supplement Fig. 3 ). In parallel, levels of 311 infectious virus in liver, kidney, and adrenal gland were also significantly reduced. Studies at day 312 5 of infection also indicated that EBOV GP∆O/rVSV loads were much reduced in the brain of 313 TIM-1 -/mice and trended lower in the testis (Supplement Fig. 4A at days -1 and 2. We verified that T cells within peripheral blood were profoundly depleted at 366 day 5 of infection by flow cytometry following immunostaining with an α-CD90 mAb (Fig. 5A) . 367