TIM-1 acts a dual-attachment receptor for Ebolavirus by interacting directly with viral GP and the PS on the viral envelope.
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.
Shuai
S
Yuan
Lei
L
Cao
Hui
H
Ling
Minghao
M
Dang
Yao
Y
Sun
Xuyuan
X
Zhang
Yutao
Y
Chen
Liguo
L
Zhang
Dan
D
Su
Xiangxi
X
Wang
Zihe
Z
Rao
D029043:Ebolavirus / Q000378:metabolism*; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism*; D000072596:Hepatitis A Virus Cellular Receptor 1; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
D006023:Glycoproteins; C491143:HAVCR1 protein, human; C448908:HAVCR2 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D000072597:Hepatitis A Virus Cellular Receptor 2; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011991:Receptors, Virus; C512411:TIMD4 protein, human; D014759:Viral Envelope Proteins; D014764:Viral Proteins