CD8(+) T-cells target the Crimean-Congo haemorrhagic fever virus Gc protein to control the infection in wild-type mice

BACKGROUND: Crimean-Congo haemorrhagic fever (CCHF) is a serious viral hemorrhagic fever caused by the CCHF virus (CCHFV). Spread by the bites of infected ticks or handling of viremic livestock, human disease is characterized by a non-specific febrile illness that can rapidly progress to fatal hemorrhagic disease. No vaccines or antivirals are available. Case fatality rates can vary but can be higher than 30%, although sub-clinical infections are often unrecognized and unreported. Yet, while most humans infected with CCHFV will survive the infection, often with little-to-no symptoms, the host responses that control the infection are unknown. METHODS: Here we investigated the role of cellular immunity in control of CCHFV infection in an immunocompetent mouse model. FINDINGS: We found that CD8(+) T-cells are crucial for efficient control of the acute infection and rapidly acquired CCHFV-specific antiviral effector functions such as production of antiviral cytokines and degranulating in response to CCHFV peptides. We further identified the minimal CD8(+) T-cell epitopes in the viral Gc proteins and that infection of mice lacking IFNγ resulted in worsened disease and higher viral loads. INTERPRETATION: Together our data suggest that CD8(+) T-cells are important for control of acute CCHFV infection likely through production of antiviral cytokines. FUNDING: This work was supported by the Intramural Research Program of the NIH.