Structure and Characterization of Crimean-Congo Hemorrhagic Fever Virus GP38
Akaash K. Mishra, Crystal L. Moyer, Dafna M. Abelson, Daniel J. Deer, Kamel El Omari, Ramona Duman, Leslie Lobel, Julius J. Lutwama, John M. Dye, Armin Wagner, Kartik Chandran, Robert W. Cross, Thomas W. Geisbert, Larry Zeitlin, Zachary A. Bornholdt, Jason S. McLellan
Abstract
Crimean-Congo hemorrhagic fever virus (CCHFV) is a priority pathogen that poses a high risk to public health. Due to the high morbidity and mortality rates associated with CCHFV infection, there is an urgent need to develop medical countermeasures for disease prevention and treatment. CCHFV GP38, a secreted glycoprotein of unknown function unique to the Nairoviridae family, was recently shown to be the target of a protective antibody against CCHFV. Here, we present the crystal structure of GP38, which revealed a novel fold with distant homology to another CCHFV glycoprotein that is suggestive of a gene duplication event. We also demonstrate that antibody 13G8 protects STAT1-knockout mice against heterologous CCHFV challenge using a clinical isolate from regions where CCHFV is endemic. Collectively, these data advance our understanding of GP38 structure and antigenicity and should facilitate future studies investigating its function.