A single mutation in Crimean-Congo hemorrhagic fever virus discovered in ticks impairs infectivity in human cells

Abstract

Crimean-Congo Hemorrhagic Fever (CCHF) is the most widely distributed tick-borne viral infection in the world. Strikingly, reported mortality rates for CCHF are extremely variable, ranging from 5 to 80% (1). CCHF virus (CCHFV, Nairoviridae) exhibits extensive genomic sequence diversity across strains (2, 3). It is currently unknown if genomic diversity is a factor contributing to variation in its pathogenicity. We obtained complete genome sequences of CCHFV directly from the tick reservoir. These new strains belong to a solitary lineage named Europe 2 that is circumstantially reputed to be less pathogenic than the epidemic strains from Europe 1 lineage. We identified a single tick-specific amino acid variant in the viral glycoprotein region that dramatically reduces its fusion activity in human cells, providing evidence that a GPC variant, present in ticks, have severely impaired function in human cells.

Comparison of Crimean-Congo Hemorrhagic Fever Virus and Aigai Virus in Life Cycle Modeling Systems Reveals a Difference in L Protein Activity

“…The MT-1303 strain is another AIGV recovered from sequences acquired directly from an infected tick. As well as demonstrating the requirement of a single amino acid in GPC to allow infection of human cells, the study also demonstrated that the MT-1303 L protein produced lower levels of reporter gene activity than the CCHFV IbAr10200 strain ( 31 ). Our data are consistent with this study and suggest that lower L protein activity is a common feature of AIGV and show that even once the cell entry species barrier is overcome, AIGV may still be less virulent.…”

“…It is also possible that any potential difference in pathogenicity is multifaceted. A recent study published by Hue et al examined the Malko Tarnovo strain (MT-1303) of AIGV (previously classified as CCHFV genotype VI/Europe II) ( 31 ). The MT-1303 strain is another AIGV recovered from sequences acquired directly from an infected tick.…”

Comparative characterization of Crimean-Congo hemorrhagic fever virus cell culture systems with application to propagation and titration methods

“…The other two cell lines, HuH-7 and BSR-T7/5, are not supplied by ATCC. HuH-7 was reportedly available from Apath, LCC [ 18 ]. It is also listed in the catalogues of the Japanese Collection of Research Bioresources (JCRB0403) and Fisher Scientific (NC0848302).…”

Crimean-Congo Hemorrhagic Fever Virus in Asia, Africa and Europe

“…However, it should be noted that a heavily mouse-passaged virus could show less variations in immunocompromised mice but will show remarkable variations when reintroduced to the tick. Furthermore, a recent study revealed a single tick-specific amino acid substitution in the viral glycoprotein region that significantly lowered the viral fusion activity in human cells, indicating that a glycoprotein precursor variant found in ticks has greatly diminished function in human cells [ 25 ].…”