Crystal structures of GI.8 Boxer virus P dimers in complex with HBGAs, a novel evolutionary path selected by the Lewis epitope

Human noroviruses (huNoVs) recognize histo-blood group antigens (HBGAs) as attachment factors, in which genogroup (G) I and GII huNoVs use distinct binding interfaces. The genetic and evolutionary relationships of GII huNoVs under selection by the host HBGAs have been well elucidated via a number of structural studies; however, such relationships among GI NoVs remain less clear due to the fact that the structures of HBGA-binding interfaces of only three GI NoVs with similar binding profiles are known. In this study the crystal structures of the P dimers of a Lewis-binding strain, the GI.8 Boxer virus (BV) that does not bind the A and H antigens, in complex with the Lewis b (Le(b)) and Le(y) antigens, respectively, were determined and compared with those of the three previously known GI huNoVs, i.e. GI.1 Norwalk virus (NV), GI.2 FUV258 (FUV) and GI.7 TCH060 (TCH) that bind the A/H/Le antigens. The HBGA binding interface of BV is composed of a conserved central binding pocket (CBP) that interacts with the β-galactose of the precursor, and a well-developed Le epitope-binding site formed by five amino acids, including three consecutive residues from the long P-loop and one from the S-loop of the P1 subdomain, a feature that was not seen in the other GI NoVs. On the other hand, the H epitope/acetamido binding site observed in the other GI NoVs is greatly degenerated in BV. These data explain the evolutionary path of GI NoVs selected by the polymorphic human HBGAs. While the CBP is conserved, the regions surrounding the CBP are flexible, providing freedom for changes. The loss or degeneration of the H epitope/acetamido binding site and the reinforcement of the Le binding site of the GI.8 BV is a typical example of such change selected by the host Lewis epitope.

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.

Comparative Study of LISS and the Condylar Support Plates in the Treatment of AO Type C Distal Femoral Fractures in Adults / 天津医药

Objective To summarize complications and early clinical effect of less invasive stabilization system and the femoral condylar support plates in treatment of AO type C distal femoral fractures. Methods We reviewed 46 patients who had internal fixation of AO type C distal femoral fractures. Of all 46 patients, 25 were with less invasive stabilization sys-tem and 21 were with femoral condylar support plates fixation. Comparative analysis was performed using intraoperative in-dex, postoperative complications and the Evanich score at follow-up. Results All 46 patients were followed up with a mean time of 19.6 months after surgery. The difference in incision length, blood loss, fracture healing time was significant between the 2 groups(P＜0.05)but not in the duration of operations and hospital stays(P>0.05). The statistical signifi-cance was also found in the total incidence of postoperative complications and the Evanich score at the last follow-up(P＜0.05). Conclusion Patients with less invasive stabilization system fixation had the characteristics of less trauma, shorter fracture healing time, less postoperative complications and better functional recovery compared with femoral condylar sup-port plates. Less invasive stabilization system had became an ideal internal fixation in treatment of AO type C distal femoral fractures.