TIM-1 acts a dual-attachment receptor for Ebolavirus by interacting directly with viral GP and the PS on the viral envelope |
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Authors: | Shuai Yuan Lei Cao Hui Ling Minghao Dang Yao Sun Xuyuan Zhang Yutao Chen Liguo Zhang Dan Su Xiangxi Wang Zihe Rao |
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Institution: | 1. National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China2. University of Chinese Academy of Sciences, Beijing 100049, China3. State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China4. College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China |
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Abstract: | Ebolavirus can cause hemorrhagic fever in humans with a mortality rate of 50%?90%. Currently, no approved vaccines and antiviral therapies are available. Human TIM1 is considered as an attachment factor for EBOV, enhancing viral infection through interaction with PS located on the viral envelope. However, reasons underlying the preferable usage of hTIM-1, but not other PS binding receptors by filovirus, remain unknown. We firstly demonstrated a direct interaction between hTIM-1 and EBOV GP in vitro and determined the crystal structures of the Ig V domains of hTIM-1 and hTIM-4. The binding region in hTIM-1 to EBOV GP was mapped by chimeras and mutation assays, which were designed based on structural analysis. Pseudovirion infection assays performed using hTIM-1 and its homologs as well as point mutants verified the location of the GP binding site and the importance of EBOV GP-hTIM-1 interaction in EBOV cellular entry. |
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Keywords: | Ebolavirus viral entry glycoprotein receptor interaction |
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