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

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.

Immunogenicity of a DNA-Based Sindbis Replicon Expressing Crimean–Congo Hemorrhagic Fever Virus Nucleoprotein

Crimean–Congo hemorrhagic fever virus (CCHFV) infrequently causes hemorrhagic fever in humans with a case fatality rate of 30%. Currently, there is neither an internationally approved antiviral drug nor a vaccine against the virus. A replicon based on the Sindbis virus vector encoding the complete open reading frame of a CCHFV nucleoprotein from a South African isolate was prepared and investigated as a possible candidate vaccine. The transcription of CCHFV RNA and recombinant protein production by the replicon were characterized in transfected baby hamster kidney cells. A replicon encoding CCHFV nucleoprotein inserted in plasmid DNA, pSinCCHF-52S, directed transcription of CCHFV RNA in the transfected cells. NIH-III heterozygous mice immunized with pSinCCHF-52S generated CCHFV IgG specific antibodies with notably higher levels of IgG2a compared to IgG1. Splenocytes from mice immunized with pSinCCHF-52S secreted IFN-γ and IL-2, low levels of IL-6 or IL-10, and no IL-4. No specific cytokine production was registered in splenocytes of mock-immunized mice (p < 0.05). Thus, our study demonstrated the expression of CCHFV nucleoprotein by a Sindbis virus vector and its immunogenicity in mice. The spectrum of cytokine production and antibody profile indicated predominantly Th1-type of an anti-CCHFV immune response. Further studies in CCHFV-susceptible animals are necessary to determine whether the induced immune response is protective.

GENETIC DIVERSITY OF THE CRIMEAN-CONGO HEMORRHAGIC FEVER VIRUSES CIRCULATING IN THE WORLD (REVIEW)

Вирус Конго-Крымской геморрагической лихорадки является возбудителем тяжелой клещевой, часто смертельной, Конго-Крымской геморрагической лихорадки, которая широко распространена во всем мире. Передача вируса Конго-Крымской геморрагической лихорадки к человеку происходит через укус клеща, раздавливание зараженных клещей или контакт с инфицированной кровью человека. Миграция вируса способна через клещей с животными и перелетных птиц, в связи с чем имеется возможность исследования географического распространения посредством генетического анализа. В этом обзоре мы стремимся обобщить самые последние данные о генетическом разнообразии вирусов Конго-Крымской геморрагической лихорадки, циркулирующих в мире. Временной и пространственный анализ многообразия штаммов вируса может послужить ключевым фактором для лучшего понимания связи серопозитивности и уровня летальности. The Crimean-Congo hemorrhagic fever virus is the causative agent of severe tick-borne, often fatal, zoonotic Crimean-Congo hemorrhagic fever, which is widespread throughout the world. Transmission of the Crimean-Congo hemorrhagic fever virus to humans occurs through a tick bite, crushing of infected ticks or contact with infected host blood. The migration of the virus is possible through ticks with animals and migratory birds, and therefore it is possible to study the geographical distribution through genetic analysis. In this review, we aim to summarize the latest data on the genetic diversity of the Crimean-Congo hemorrhagic fever viruses circulating in the world. The temporal and spatial analysis of the diversity of virus strains can serve as a key factor for a better understanding of the relationship between seropositivity and the mortality rate.

Immune responses in multiple hosts to Nucleocapsid Protein (NP) of Crimean-Congo Hemorrhagic Fever Virus (CCHFV)

In 2019, the World Health Organization declared 3 billion to be at risk of developing Crimean Congo Hemorrhagic Fever (CCHF). The causative agent of this deadly infection is CCHFV. The data related to the biology and immunology of CCHFV are rather scarce. Due to its indispensable roles in the viral life cycle, NP becomes a logical target for detailed viral immunology studies. In this study, humoral immunity to NP was investigated in CCHF survivors, as well as in immunized mice and rabbits. Abundant antibody response against NP was demonstrated both during natural infection in humans and following experimental immunizations in mice and rabbits. Also, cellular immune responses to recombinant NP (rNP) was detected in multispecies. This study represents the most comprehensive investigation on NP as an inducer of both humoral and cellular immunity in multiple hosts and proves that rNP is an excellent candidate warranting further immunological studies specifically on vaccine investigations.