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

抄録

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.

収録刊行物

• Journal of virology

  Journal of virology 89 (12), 6481-6493, 2015-06

  American Society for Microbiology

詳細情報

• CRID: 1050845763948360704
• NII論文ID: 120005621883
• NII書誌ID: AA00708779
• ISSN: 10985514
• ISSN: 0022538X
• HANDLE: 2115/59504
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
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  • CiNii Articles