부산대학교 도서관

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic tick-borne virus, prevalent in more than 30 countries worldwide. Human infection by this virus leads to severe illness, with an average case fatality of 40%. There is currently no approved vaccine or drug to treat the disease. Neutralizing antibodies are a promising approach to treat virus infectious diseases. This study generated 37 mouse-derived specific monoclonal antibodies against CCHFV Gc subunit. Neutralization assays using pseudotyped virus and authentic CCHFV identified Gc8, Gc13, and Gc35 as neutralizing antibodies. Among them, Gc13 had the highest neutralizing activity and binding affinity with CCHFV Gc. Consistently, Gc13, but not Gc8 or Gc35, showed in vivo protective efficacy (62.5% survival rate) against CCHFV infection in a lethal mouse infection model. Further characterization studies suggested that Gc8 and Gc13 may recognize a similar, linear epitope in domain II of CCHFV Gc, while Gc35 may recognize a different epitope in Gc. Cryo-electron microscopy of Gc-Fab complexes indicated that both Gc8 and Gc13 bind to the conserved fusion loop region and Gc13 had stronger interactions with sGc-trimers. This was supported by the ability of Gc13 to block CCHFV GP-mediated membrane fusion. Overall, this study provides new therapeutic strategies to treat CCHF and new insights into the interaction between antibodies with CCHFV Gc proteins. Author summary: Crimean-Congo hemorrhagic fever (CCHF) is a priority disease by the World Health Organization (WHO). It is a deadly viral infectious disease with case fatalities up to 40%, and no approved vaccine or treatment. Neutralizing antibodies are a promising approach toward treating viral infections, as exemplified in other hemorrhagic fevers such as Ebola. Currently, there are few reports of efficient neutralizing antibodies against CCHF virus (CCHFV). This study successfully screened mouse-derived monoclonal antibodies with high in vitro neutralizing activity and in vivo protective efficacy against CCHFV infection. Among those, mAb Gc13 was the most efficient because it strongly bound to the highly conserved fusion loop regions of the CCHFV Gc subunit, thus blocking the crucial virus membrane fusion process. This study highlights the potential of neutralizing antibody-based strategies for CCHF treatment. [ABSTRACT FROM AUTHOR]