著者

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

出版者

American Society for Microbiology

雑誌

Journal of virology (ISSN:0022538X)

巻号頁・発行日

vol.89, no.12, pp.6481-6493, 2015-06

被引用文献数

64

---

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.