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

Sara Lado,Jeremy V Camp,Dafalla O Kannan,Petr Horin,Pamela A Burger,Jolanta Kolodziejek,Norbert Nowotny,Tom Loney,Martin Plasil,Pia Weidinger,Jan Futas

doi:10.3390/cells11010008

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.

Highlights

IntroductionCamelids have the unique ability to generate homodimeric immunoglobulins (Igs) in addition to conventional antibodies, where the antigen-binding fragment of these specific IgGs is reduced to a single variable domain lacking the light chain [1]
The material was collected during two field seasons (March/April 2019 and October 2019) in three locations in the United Arab Emirates (UAE): (1) the largest national livestock market (April 2019, n = 37; October 2019, n = 39); (2) a desert wildlife reserve with camels primarily used for tourism (April 2019, n = 30); and (3) a Bedouin family-owned farm with camels primarily raised for racing and trading (March 2019, n = 15) (Table S1)
Animals with antibodies were present in all three locations in the UAE, showing equal exposure to past infections

Summary

Introduction

Camelids have the unique ability to generate homodimeric immunoglobulins (Igs) in addition to conventional antibodies, where the antigen-binding fragment of these specific IgGs is reduced to a single variable domain lacking the light chain [1]. Due to their reduced size and resistance to high temperatures and chemical compounds, these nanobodies can be used for both clinical applications and antiviral therapy by transporting therapeutic agents into different body parts, as well as crossing the blood–brain barrier [2]. Recent studies have shown that nanobodies produced by camelids can effectively neutralize betacoronaviruses [3,4] and block SARS-CoV-2 infection [5]

Methods

Results

Conclusion