Interaction between TIM-1 and NPC1 is important for cellular entry of ebola virus

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

Research output: Contribution to journalArticle

34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6481-6493
Number of pages13
JournalJournal of Virology
Volume89
Issue number12
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Kuroda, M., Fujikura, D., Nanbo, A., Marzi, A., Noyori, O., Kajihara, M., Maruyama, J., Matsuno, K., Miyamoto, H., Yoshida, R., Feldmann, H., & Takada, A. (2015). Interaction between TIM-1 and NPC1 is important for cellular entry of ebola virus. Journal of Virology, 89(12), 6481-6493. https://doi.org/10.1128/JVI.03156-14