TIM-family Proteins Promote Infection of Multiple Enveloped Viruses through Virion-associated Phosphatidylserine

Jemielity, Stephanie; Wang, Jinyize J.; Chan, Ying Kai; Ahmed, Asim A.; Li, Wenhui; Monahan, Sheena; Bu, Xia; Farzan, Michael; Freeman, Gordon J.; Umetsu, Dale T.; DeKruyff, Rosemarie H.; Choe, Hyeryun

hTIM1-mediated enhancement of pseudovirus and VLP entry is PS dependent hTIM1 is a receptor involved in the PS-mediated uptake of apoptotic cells [21] . To test the hypothesis that hTIM1 may broadly increase viral entry because it binds PS on viral membranes rather than to specific viral glycoproteins, we compared viral usage of a hTIM1 variant defective in binding PS with that of wt hTIM1. The mutant variant, hereafter referred to as AA-hTIM1, has two mutations in the PS-binding pocket that are known to nearly abrogate PS binding [19, 21] . Indeed, when these receptors were overexpressed in 293T cells we found that AA-hTIM1 was unable to enhance the entry of any pseudovirus tested (Fig. 3A) despite efficient AA-hTIM1 expression (Fig. 3B ). This indicates that viral hTIM1 usage is PS-dependent.