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.Electronic supplementary materialThe online version of this article (doi:10.1007/s13238-015-0220-y) contains supplementary material, which is available to authorized users.

The majority of outbreaks of the common cold are caused by rhinoviruses. The 2A protease (2A) of human rhinoviruses (HRVs) is known to play important roles in the propagation of the virus and the modulation of host signal pathways to facilitate viral replication. The 2A from human rhinovirus C15 (HRV-C15) has been expressed in Escherichia coli and purified by affinity chromatography, ion-exchange chromatography and gel-filtration chromatography. The crystals diffracted to 2.6 Å resolution. The structure was solved by molecular replacement using the structure of 2A from coxsackievirus A16 (CVA16) as the search model. The structure contains a conserved His-Asp-Cys catalytic triad and a Zn-binding site. Comparison with other 2A structures from enteroviruses reveals that the substrate-binding cleft of 2A from HRV-C15 exhibits a more open conformation, which presumably favours substrate binding.