Journal Article Interaction between TIM-1 and NPC1 Is Important for Cellular Entry of Ebola Virus

Kuroda, Makoto  ,  Fujikura, Daisuke  ,  Nanbo, Asuka  ,  Marzi, Andrea  ,  Noyori, Osamu  ,  Kajihara, Masahiro  ,  Maruyama, Junki  ,  Matsuno, Keita  ,  Miyamoto, Hiroko  ,  Yoshida, Reiko  ,  Feldmann, Heinz  ,  Takada, Ayato

89 ( 12 )  , pp.6481 - 6493 , 2015-06 , American Society for Microbiology
Multiple host molecules are known to be involved in the cellular entry of filoviruses, including Ebola virus (EBOV); T-cell immunoglobulin and mucin domain 1 (TIM-1) and Niemann-Pick C1 (NPC1) have been identified as attachment and fusion receptors, respectively. However, the molecular mechanisms underlying the entry process have not been fully understood. We found that TIM-1 and NPC1 colocalized and interacted in the intracellular vesicles where EBOV glycoprotein (GP)-mediated membrane fusion occurred. Interestingly, a TIM-1-specific monoclonal antibody (MAb), M224/1, prevented GP-mediated membrane fusion and also interfered with the binding of TIM-1 to NPC1, suggesting that the interaction between TIM-1 and NPC1 is important for filovirus membrane fusion. Moreover, MAb M224/1 efficiently inhibited the cellular entry of viruses from all known filovirus species. These data suggest a novel mechanism underlying filovirus membrane fusion and provide a potential cellular target for antiviral compounds that can be universally used against filovirus infections.

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