Innate immune signalling induced by Crimean-Congo haemorrhagic fever virus proteins in vitro

Crimean-Congo haemorrhagic fever orthonairovirus (CCHFV) is a tick-borne viral zoonosis associated with haemorrhagic fever in humans. The World Health Organisation identified CCHFV as a priority pathogen for research. The disease is widespread globally with regions of endemicity in Africa, Asia and eastern Europe; however, the emergence and re-emergence of disease in endemic and non-endemic regions is a cause for concern. Additionally, the lack of rapid point-of-care assays, a vaccine or therapeutic interventions approved for use in humans complicates the control and management of disease, which requires an improved understanding of the virus-host interactions. Viruses have co-evolved with their host/s. Dysregulation of the immune response is a common strategy utilised to evade immune detection and clearance. The innate immune response is a robust non-specific response to infection with the aim of limiting virus replication and spread while activating the adaptive immune response that mediates virus clearance and protection. In this study, innate immune modulation by selected non-structural CCHFV proteins, including the NSM protein and ovarian-tumour like (OTU) protease, and Hazara orthonairovirus (HAZV), a possible model for CCHFV, was investigated. The CCHFV NSM protein, encoded on the M-segment, was expressed in vitro to evaluate the ability of the protein to modulate innate immune signalling. In South Africa, isolates containing an M-segment that are genetically related to other South African isolates (non-reassortant) and isolates containing an M-segment that are genetically similar to Asian isolates (reassortant) have been identified. The CCHFV NSM proteins from both reassortant and non-reassortant CCHFV isolates were evaluated. Despite 92,88% amino acid sequence similarity between the reassortant and non-reassortant NSM protein, the non-reassortant NSM protein downregulated key innate immune markers, including DDX58 (RIG-1), IFNB1, IFNAR1 and STAT1, whereas t
Poliomyelitis Research Foundation (PRF)
National Research Foundation (NRF)
University of the Free State