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

Several recent findings suggest that negatively-charged phospholipids like PS might play a role in mediating virus entry. PS was shown to be exposed on the membranes of various enveloped viruses, including Pichinde virus, vesicular stomatitis virus (VSV) and the intracellular mature virion form of Vaccinia virus [32, 33] . This is likely a common feature of most enveloped viruses, as virusinfected cells were shown to overexpress PS on their plasma membranes [32] [33] [34] . In addition, the entry of lentiviral pseudoviruses bearing the GPs of Sindbis (SINV), Ross River (RRV) and Baculo virus was enhanced in a PS-dependent manner by the TAM receptor tyrosine kinase Axl [35] . Axl has also been shown to promote EBOV and MARV entry [11] . Finally, an antibody targeting anionic phospholipids effectively rescued rodents from lethal challenges by either Pichinde virus or mouse cytomegalovirus, demonstrating in vivo contribution of anionic phospholipids to the infectivity of these viruses [33] .