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

Abstract

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.

Journal

• Journal of virology

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

  American Society for Microbiology

Details

• CRID: 1050845763948360704
• NII Article ID: 120005621883
• NII Book ID: AA00708779
• ISSN: 10985514
• ISSN: 0022538X
• HANDLE: 2115/59504
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles