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

Experimental infections in animal models have shown that macrophages are early targets for the replication of several viruses [55, 56] . We therefore assessed the contribution of PS receptors to viral entry in mouse peritoneal macrophages, which are known to express TIM4 [21] and other PS receptors. To be able to detect viral entry instantaneously, we used VLPs consisting of EBOV VP40 matrix proteins fused to b-lactamase (VP40-Bla VLPs [8] ) for infection. As shown in Figure 7D , the entry of VP40-Bla VLPs bearing EBOV GP was inhibited by 45% in the presence of PScontaining liposomes at 10 mM, reflecting as expected that other host cell molecules also play a role in virus infection. In contrast, the entry of the same VLPs bearing LASV GP was only little inhibited (by 8%). The blocking effect was specific for PS, as liposomes consisting of only PC did not inhibit either VLPs. These data are consistent with the notion that PS receptors can help potentiate viral infection in macrophages.