Crimean-Congo Hemorrhagic Fever Virus Past Infections Are Associated with Two Innate Immune Response Candidate Genes in Dromedaries

Abstract

Dromedaries are an important livestock, used as beasts of burden and for meat and milk production. However, they can act as an intermediate source or vector for transmitting zoonotic viruses to humans, such as the Middle East respiratory syndrome coronavirus (MERS-CoV) or Crimean-Congo hemorrhagic fever virus (CCHFV). After several outbreaks of CCHFV in the Arabian Peninsula, recent studies have demonstrated that CCHFV is endemic in dromedaries and camel ticks in the United Arab Emirates (UAE). There is no apparent disease in dromedaries after the bite of infected ticks; in contrast, fever, myalgia, lymphadenopathy, and petechial hemorrhaging are common symptoms in humans, with a case fatality ratio of up to 40%. We used the in-solution hybridization capture of 100 annotated immune genes to genotype 121 dromedaries from the UAE tested for seropositivity to CCHFV. Through univariate linear regression analysis, we identified two candidate genes belonging to the innate immune system: FCAR and CLEC2B. These genes have important functions in the host defense against viral infections and in stimulating natural killer cells, respectively. This study opens doors for future research into immune defense mechanisms in an enzootic host against an important zoonotic disease.

Keywords: Camelus dromedarius; Old World camel; in-solution hybridization capture; tick; vector-borne infection; zoonosis.

Figure 1

Principal component analysis of the population structure at three collection sites over two sampling periods. Variance explained by Coordinates 1 and 2 are given as percentages on the axes’ labels. Individual animals are plotted on the first two principal components, colored by sampling site (livestock market (“L.Market”) over two sampling periods (April and October 2019 denoted by red and dark blue, respectively), Dubai Desert Conservation Reserve (“Wild.Reserve”) denoted by yellow, and a Bedouin camel farm (“Camel.Farm”) denoted by grey). The inset shows a bar plot of the eigenvalues for the first 10 principal components.

Figure 2

Univariate logistic regression results. (a) QQ plot and (b) Manhattan plot, with false discovery rate (FDR) threshold depicted in blue. −log₁₀(p) values for SNPs alternate from green to orange to delineate chromosomes adjacent in the plots. C45 corresponds to Contig45, an unplaced scaffold in the CamDro3 reference.