The DEVD motif of Crimean-Congo hemorrhagic fever virus nucleoprotein is essential for viral replication in tick cells
Cristiano Salataa,b, Vanessa Monteil b,c, Helen Karlbergb,c, Michele Celestinoa, Stephanie Devignotd, Mikael Lejone, Lesley Bell-Sakyif, Éric Bergerong, Friedemann Weberd, Ali Mirazimib,c,e
aDepartment of Molecular Medicine, University of Padova, IT-35121 Padova, Italy, bDepartment of Microbiology, Public Health Agency of Sweden, SE-171 82 Solna, Sweden, cDepartment of Laboratory Medicine, Karolinska University Hospital and KI, SE-14186 Huddinge Stockholm, Sweden, dInstitute for Virology, FB10-Veterinary Medicine, Justus Liebig University Giessen, DE-35392 Giessen, Germany, eNational Veterinary Institute, SE-756 51, Uppsala, fDepartment of Infection Biology, Institute of Infection and Global Health, University of Liverpool
Liverpool Science Park IC2, Liverpool L3 5RF, United Kingdom., gViral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA-30333, USA
Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic viral disease that is asymptomatic in infected animals, but a serious threat to humans developing a hemorrhagic syndrome with a high case fatality rate. CCHF virus (CCHFV) has been found in several species of ticks; in particular, members of the genus Hyalomma seem to be the principal vectors as they play an important role as a natural reservoir. In this study, we developed a model system for investigating Nairovirus replication in their natural host cells. We found that CCHFV and HAZV chronically infected HAE/CTVM8 and HAE/CTVM9 tick cells without cytopathic effects, the behavior of the viruses differ at the early stage of infection showing a different susceptibility and permissivity of tick cells to CCHFV and HAZV. By using this model system, we have demonstrated that the DEVD domain in the nucleoprotein of CCHFV has an essential function on virus replication in the cells of its natural reservoir. Briefly, we show that the mutation of the DEVD domain positively affect the replication efficiency of CCHFV in human cells but most interestingly, strongly inhibits viral replication in Hyalomma-derived tick cell lines displaying that it is essential for the infection of ticks.