Crimean-Congo Hemorrhagic Fever Virus RNA Research Articles

Epidemiologic Survey of Crimean-Congo Hemorrhagic Fever Virus in Suids, Spain.

We conducted a cross-sectional study in wild boar and extensively managed Iberian pig populations in a hotspot area of Crimean-Congo hemorrhagic fever virus (CCHFV) in Spain. We tested for antibodies against CCHFV by using 2 ELISAs in parallel. We assessed the presence of CCHFV RNA by means of reverse transcription quantitative PCR protocol, which detects all genotypes. A total of 113 (21.8%) of 518 suids sampled showed antibodies against CCHFV by ELISA. By species, 106 (39.7%) of 267 wild boars and 7 (2.8%) of 251 Iberian pigs analyzed were seropositive. Of the 231 Iberian pigs and 231 wild boars analyzed, none tested positive for CCHFV RNA. These findings indicate high CCHFV exposure in wild boar populations in endemic areas and confirm the susceptibility of extensively reared pigs to CCHFV, even though they may only play a limited role in the enzootic cycle.

Discovery of baloxavir sodium as a novel anti-CCHFV inhibitor: Biological evaluation of in vitro and in vivo

Crimean–Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic bunyavirus with a fatality rate of up to 40%. Currently, there are no licensed antiviral drugs for the treatment of CCHF; thus, the World Health Organization (WHO) listed the disease as a priority. A unique viral transcription initiation mechanism called “cap-snatching” is shared by influenza viruses and bunyaviruses. Thus, we tested whether baloxavir (an FDA-approved anti-influenza drug that targets the “cap-snatching” mechanism) could inhibit CCHFV infection. In cell culture, baloxavir acid effectively inhibited CCHFV infection and targeted CCHFV RNA transcription/replication. However, it has weak oral bioavailability. Baloxavir marboxil (the oral prodrug of baloxavir) failed to protect mice against a lethal dose challenge of CCHFV. To solve this problem, baloxavir sodium was synthesized owing to its enhanced aqueous solubility and pharmacokinetic properties. It consistently and significantly improved survival rates and decreased tissue viral loads. This study identified baloxavir sodium as a novel scaffold structure and mechanism of anti-CCHF compound, providing a promising new strategy for clinical treatment of CCHF after further optimization.

Transmission Dynamics of Crimean-Congo Haemorrhagic Fever Virus (CCHFV): Evidence of Circulation in Humans, Livestock, and Rodents in Diverse Ecologies in Kenya.

Crimean-Congo haemorrhagic fever virus (CCHFV) is the causative agent of CCHF, a fatal viral haemorrhagic fever disease in humans. The maintenance of CCHFV in the ecosystem remains poorly understood. Certain tick species are considered as vectors and reservoirs of the virus. Diverse animals are suspected as amplifiers, with only scarce knowledge regarding rodents in virus epidemiology. In this study, serum samples from febrile patients, asymptomatic livestock (cattle, donkeys, sheep, and goats), and peridomestic rodents from Baringo (Marigat) and Kajiado (Nguruman) counties within the Kenyan Rift Valley were screened for acute CCHFV infection by RT-PCR and for CCHFV exposure by ELISA. RT-PCR was performed on all livestock samples in pools (5-7/pool by species and site) and in humans and rodents individually. CCHFV seropositivity was significantly higher in livestock (11.9%, 113/951) compared to rodents (6.5%, 6/93) and humans (5.9%, 29/493) (p = 0.001). Among the livestock, seropositivity was the highest in donkeys (31.4%, 16/51), followed by cattle (14.1%, 44/310), sheep (9.8%, 29/295) and goats (8.1%, 24/295). The presence of IgM antibodies against CCHFV was found in febrile patients suggesting acute or recent infection. CCHFV RNA was detected in four pooled sera samples from sheep (1.4%, 4/280) and four rodent tissues (0.83%, 4/480) showing up to 99% pairwise nucleotide identities among each other. Phylogenetic analyses of partial S segment sequences generated from these samples revealed a close relationship of 96-98% nucleotide identity to strains in the CCHFV Africa 3 lineage. The findings of this study suggest active unnoticed circulation of CCHFV in the study area and the involvement of livestock, rodents, and humans in the circulation of CCHFV in Kenya. The detection of CCHF viral RNA and antibodies against CCHFV in rodents suggests that they may participate in the viral transmission cycle.

Favipiravir and Ribavirin protect immunocompetent mice from lethal CCHFV infection

Crimean-Congo hemorrhagic fever virus (CCHFV) causes Crimean-Congo hemorrhagic fever (CCHF) in humans with high morbidity and mortality. Currently, there is neither an approved antiviral drug nor a vaccine against CCHFV. In this study, we describe a lethal model of CCHFV infection using a mouse-adapted strain of CCHFV (MA-CCHFV) in adult wild-type male mice. Infected mice developed high viral loads, tissue pathology, and inflammatory immune responses before ultimately succumbing to the infection. We used the model to evaluate the protective efficacy of nucleoside analogs monulpiravir, favipiravir, ribavirin, the antibiotic tigecycline and the corticosteroids dexamethasone and methylprednisolone against lethal CCHFV infection. Tigecycline, monulpiravir and the corticosteroids failed to protect mice from lethal MA-CCHFV infection. In contrast, favipiravir and ribavirin protected animals from clinical disease and death even when treatment was delayed. Despite demonstrating uniform protection, CCHFV RNA persisted in survivors treated with favipiravir and ribavirin. Nevertheless, the study demonstrated the anti-CCHFV efficacy of favipiravir and ribavirin in a model with intact innate immunity and establishes this model for continued development of CCHFV countermeasures.

Crimean-Congo Hemorrhagic Fever Virus Survey in Humans, Ticks, and Livestock in Agnam (Northeastern Senegal) from February 2021 to March 2022.

Crimean–Congo hemorrhagic fever virus (CCHFV) is widespread in Asia, Europe, and Africa. In Senegal, sporadic cases of CCHFV have been reported since 1960. Bordering Mauritania in northeastern Senegal, Agnam is an arid area in the region of Matam where CCHFV is endemic, which harbors a pastoralist community. Given the drought conditions of Agnam, inhabitants are in constant movement with their animals in search of pasture, which brings them into contact with pathogens such as arboviruses. To identify CCHFV in this area, we established a One Health site in order to analyze animal livestock, ticks and human samples collected over a one-year period by qRT-PCR and ELISA. Our analysis showed one (1/364) patient carried anti-CCHFV IgM and thirty-seven carried anti-CCHFV IgG (37/364). In livestock, anti-CCHFV IgG was detected in 13 (38.24%) of 34 sentinel sheep. The risk of CCHFV infection increased significatively with age in humans (p-value = 0.00117) and sheep (p-value = 1.18 × 10−11). Additional risk factors for CCHFV infection in sheep were dry seasons (p-value = 0.004) and time of exposure (p-value = 0.007). Furthermore, we detected a total of three samples with CCHFV RNA within Rhipicephalus evertsi evertsi and Rhipicephalus guilhoni tick species. Our results highlighted the usefulness of a One Health survey of CCHFV in pastoral communities at risk of arboviruses.

The Prevalence and Genetic Variants of the CCHF Virus Circulating among Ticks in the Southern Regions of Kazakhstan.

Crimean–Congo hemorrhagic fever (CCHF) disease cases are registered annually in endemic regions of Kazakhstan. To study the prevalence of various Crimean–Congo hemorrhagic fever virus (CCHFV) genotypes, a total of 694 ticks were collected from southern regions of Kazakhstan in 2021. Hyalomma marginatum (n = 323) (46.5%), Hyalomma anatolicum (n = 138) (19.9%), Hyalomma asiaticum (n = 126) (18.2%), Hyalomma scupense (n = 80) (11.5%) and Ixodes ricinus (n = 27) (3.9%) were collected using the standardized flagging technique from the environment. All the tick samples were analyzed for the presence of CCHFV RNA by RT-PCR. The CCHF-positive samples were found within three Hyalomma asiaticum and one Ixodes ricinus tick sample. For the first time in Kazakhstan, infection of the Ixodes ricinus tick with CCHFV was detected. The results of sequencing and analysis of the S-gene fragment showed that the Asia 1 and Asia 2 CCHF genotypes circulate in the southern regions of Kazakhstan. Viruses isolated in the Zhambyl and Turkestan regions are assigned to the Asia-2 genotype, whereas the virus isolated in the Kyzylorda region to the Asia-1 genotype.

Crimean-Congo hemorrhagic fever virus circulating among sheep of Portugal: a nationwide serosurvey assessment.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a widespread zoonotic pathogen that can cause mild to severe hemorrhagic disease in humans. CCHFV may be transmitted through direct contact with tissue or blood of viremic animals; however, the primary transmission route is through infected tick bites. CCHFV RNA has been detected in ticks feeding on domestic and wild animals in western Spain, suggesting an established circulation of CCHFV in Western Europe. Ruminants have been recognized as important CCHFV reservoirs and have been linked to human cases in endemic regions. Given the emergence of CCHF in neighboring Spain, and a report of two CCHFV seropositive humans in southern Portugal in 1985, we investigated the potential circulation of this virus in the country by performing a nationwide anti-CCHFV IgG serosurvey in sentinel sheep of Portugal. Sera (n = 459) randomly selected from widely distributed farms (n = 20) of Portugal were tested using a commercial double-antigen enzyme-linked immunosorbent assay, yielding an overall seroprevalence of 0.4% (95% confidence interval [CI] 0.04-1.56%). Positive sheep were from the southern region of Portugal (Alentejo region), which raise the seroprevalence of this region to 0.74% (95% CI 0.09-2.66%). This is the first study reporting the presence of CCHFV antibodies in sheep of Portugal, thus suggesting a geographical expansion of CCHFV to this country. It seems likely that CCHFV may exist focally in southern Portugal.

Lack of Evidence for Crimean–Congo Hemorrhagic Fever Virus in Ticks Collected from Animals, Corsica, France

In Corsica, France, 9.1% of livestock serum samples collected during 2014–2016 were found to have antibodies against Crimean–Congo hemorrhagic fever virus (CCHFV), an emerging tickborne zoonotic disease. We tested 8,051 ticks for CCHFV RNA and Nairovirus RNA. The results indicate that Corsica is not a hotspot for CCHFV.

Ticks and prevalence of tick-borne pathogens from domestic animals in Ghana

BackgroundTicks are important vectors of various pathogenic protozoa, bacteria and viruses that cause serious and life-threatening illnesses in humans and animals worldwide. Estimating tick-borne pathogen prevalence in tick populations is necessary to delineate how geographical differences, environmental variability and host factors influence pathogen prevalence and transmission. This study identified ticks and tick-borne pathogens in samples collected from June 2016 to December 2017 at seven sites within the Coastal, Sudan and Guinea savanna ecological zones of Ghana.MethodsA total of 2016 ticks were collected from domestic animals including cattle, goats and dogs. Ticks were morphologically identified and analysed for pathogens such as Crimean-Congo haemorrhagic fever virus (CCHFV), Alkhurma haemorrhagic fever virus (AHFV), Rickettsia spp. and Coxiella burnetii using polymerase chain reaction assays (PCR) and sequence analysis.ResultsSeven species were identified, with Amblyomma variegatum (60%) most frequently found, followed by Rhipicephalus sanguineus sensu lato (21%), Rhipicephalus spp. (9%), Hyalomma truncatum (6%), Hyalomma rufipes (3%), Rhipicephalus evertsi (1%) and Rhipicephalus (Boophilus) sp. (0.1%). Out of 912 pools of ticks tested, Rickettsia spp. and Coxiella burnetii DNA was found in 45.6% and 16.7% of pools, respectively, whereas no CCHFV or AHFV RNA were detected. Co-infection of bacterial DNA was identified in 9.6% of tick pools, with no statistical difference among the ecozones studied.ConclusionsBased on these data, humans and animals in these ecological zones are likely at the highest risk of exposure to rickettsiosis, since ticks infected with Rickettsia spp. displayed the highest rates of infection and co-infection with C. burnetii, compared to other tick-borne pathogens in Ghana.Graphical

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.

Identification of a novel lineage of Crimean-Congo haemorrhagic fever virus in dromedary camels, United Arab Emirates.

Crimean-Congo haemorrhagic fever virus (CCHFV) is a tick-borne virus causing Crimean-Congo haemorrhagic fever (CCHF), a disease reported to have a high fatality rate in numerous countries. The virus is geographically widespread due to its vector, and numerous wild and domestic animals can develop asymptomatic infection. Serological and limited molecular evidence of CCHFV has previously been reported in Camelus dromedarius (the dromedary, or one-humped camel) in the United Arab Emirates (UAE). In this study, 238 camel samples were screened for CCHFV RNA where 16 camel samples were positive for CCHFV by RT-PCR. Analysis of full-length CCHFV genome sequences revealed a novel lineage in camels from the UAE, and potential reassortment of the M segment of the genome.

Monitoring Crimean-Congo haemorrhagic fever virus RNA shedding in body secretions and serological status in hospitalised patients, Turkey, 2015.

IntroductionCrimean-Congo haemorrhagic fever (CCHF) is a tick-borne disease in Africa, Asia, the Balkan peninsula, the south-east of Europe and the Middle East, with mortality rates of 3–30%. Transmission can also occur through contact with infected animals or humans.AimThis observational, prospective case series aimed to investigate detectable viral genomic RNA in whole-body fluids and antibody dynamics in consecutive daily samples of patients diagnosed with CCHF until discharge from hospital.MethodsWe tested 18 patients and 824 swabs and sera with RT-PCR and 125 serum samples serologically.ResultsThe longest duration until clearance of viral RNA was 18 days from serum collection and 18, 15, 13, 19 and 17 days, respectively, from nasal, oral, genital (urethral or vaginal) and faecal swab, and urine. In seven patients, viral load decreased in serum at the same time as it increased in urine or persisted at the same logarithmic values. Despite clearance in serum, viral RNA was detected in faeces and genital swabs in two and three patients, respectively. Viral clearance from body fluids occurred earlier than from serum in eight patients on ribavirin treatment. The shortest seroconversion time was 3 days after symptom onset for IgM and IgG. Seroconversion of IgG occurred until Day 14 of symptoms.ConclusionWe report persistence of viral RNA in urine, faeces and genital swabs despite serum clearance. This may indicate a need for extending isolation precautions, re-evaluating discharge criteria and transmission risk after discharge, and considering oral swabs as a less invasive diagnostic alternative.

Assessing the role of migratory birds in the introduction of ticks and tick-borne pathogens from African countries: An Italian experience

The continuous flow of billions of birds between Africa and Europe creates an “ecological bridge” between physically remote areas. Migratory birds fly south from their breeding grounds during late summer/fall and fly back in spring. These movements regulate the spread of internal and external parasites, as well as pathogens of potential public health concern. The aim of the present study was to investigate the possible introduction of exotic tick species and tick-borne pathogens into Europe via migratory birds. At the bird observatory of Ventotene island (Italy), 443 feeding ticks were collected from 249 birds captured and ringed during their northbound migration in spring 2013. Each tick was identified by morphological and molecular methods and then tested for bacterial and viral pathogens: Borrelia burgdorferi s.l., Rickettsia spp., Ehrlichia ruminantium and Coxiella burnetii, Crimean Congo haemorrhagic fever virus (CCHFV) and Flavivirus. Morphological and molecular identification confirmed Hyalomma rufipes as the most abundant species among the collected arthropods (366/443; 82.6%) followed by Hyalomma marginatum (10/433; 2.3%). Rickettsia aeschlimannii was identified in 158 ticks, while one engorged Amblyomma variegatum nymph was infected with Rickettsia africae. The other bacteria were not detected in any specimen. Among viruses, RNA belonging to West Nile virus and other Flavivirus were detected whereas all ticks were negative for CCHFV RNA. These results confirm how migratory birds play a role in carrying Rickettsia-infected ticks, as well as viruses of zoonotic importance, from Africa into Europe. To what extent tick species are capable of establishing a permanent population once introduced in naïve areas, is far from defined and deserve further investigation.

Spatial and Phylodynamic Survey on Crimean-Congo Hemorrhagic Fever Virus Strains in Northeast of Iran

Background: Crimean-Congo hemorrhagic fever (CCHF) is asymptomatic in infected animals, yet the virus poses a serious threat to humans causing a symptomatic, hemorrhagic disease with a high case-fatality rate. Numerous genera of ticks serve as both vectors and reservoirs of the Crimean-Congo hemorrhagic fever virus (CCHFV). Objectives: The aim of the present study is to determine the CCHFV prevalence in ticks from northeast Iran to establish a phylogenetic relationship of the tick-derived CCHFV strains circulating in Iran. Methods: During April to June 2015, a total of 93 hard ticks were collected from different animals in the Damghan district. The S-segment of positive samples was fully sequenced using the Sanger technique. A total of 142 CCHFV sequences comprised full-length of CCHFV sequences obtained in this study were aligned using the MAFFT algorithm, then phylogenetic tree was constructed using Geneious v 7.1.8. Results: The identified tick species included Hyalomma marginatum (6.5%), Hy. dromedarii (21.5%), Hy. anatolicum (15.1%), Hy. asiaticum (3.2%) and Hy. schulzei (2.2%), as well as Rhipicephalus sanguineus (47.3%). The CCHFV RNA was detected in 4 samples of 93 tick samples (4.3%) by RT-PCR. A total of 4 CCHFV sequences were obtained in this study clustered within clade IV (Asia-1 and Asia-2). Conclusions: We demonstrated that 4 species of hard ticks could be a vector for CCHFV in Iran. In addition, our findings indicate the circulation of CCHFV clade IV strain in the northeast of Iran and provide a solid base for more targeted surveillance and prevention programs in Iran.

A new strain of Crimean-Congo hemorrhagic fever virus isolated from Xinjiang, China.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic tick-borne virus with a fatality rate of up to 50% in humans. CCHFV is widely distributed in countries around the world. Outbreaks of CCHFV infection in humans have occurred in prior years in Xinjiang Province, China. Epidemiological surveys have detected CCHFV RNA in ticks and animals; however, few isolates were identified. In this study, we identified and isolated a new CCHFV strain from Hyalomma asiaticum asiaticum ticks collected from north of Tarim Basin in Xinjiang, China. A preliminary investigation of infection and antigens expression of CCHFV was performed in newborn mice. The target tissues for CCHFV replication in newborn mice were identified. The analysis of the phylogenetic relationships with other Chinese strains suggested that diverse genotypes of CCHFV have circulated in Xinjiang for years. These findings provide important insights into our understanding of CCHFV infection and evolution as well as disease prevention and control for local residents.

Vector prevalence and detection of Crimean-Congo haemorrhagic fever virus in Golestan Province, Iran

Crimean-Congo haemorrhagic fever virus (CCHFV) causes severe disease with fatality rate of 30%. The virus is transmitted to humans through the bite of an infected tick, direct contact with the products of infected livestock as well as nosocomially. The disease occurs sporadically throughout many of African, Asian and European countries. Different species of ticks serve either as vector or reservoir for CCHFV. This study was aimed to determine the prevalence of CCHFV in hard ticks (Ixodidae) in the Golestan Province of Iran. A molecular survey was conducted on hard ticks (Ixodidae) isolated from six counties in Golestan Province, north of Iran during 2014-15. The ticks were identified using morphological characteristics and presence of CCHFV RNA was detected using RT-PCR. Data revealed the presence of CCHFV in 5.3% of the ticks selected for screening. The infected ticks belonged to Hyalomma dromedarii, Hy. anatolicum, Hy. marginatum and Rhipicephalus sanguineus species. The study demonstrated that Hyalomma ticks are the main vectors of CCHFV in Golestan Province. Thus, preventive strategies such as using acaricides and repellents in order to avoid contact with Hyalomma ticks are proposed.

Serological and Virological Evidence of Crimean-Congo Haemorrhagic Fever Virus Circulation in the Human Population of Borno State, Northeastern Nigeria.

BackgroundDespite several studies on the seroprevalence of antibodies against Crimean-Congo Haemorrhagic Fever virus (CCHFV) from humans and cattle in Nigeria, detailed investigation looking at IgG and IgM have not been reported. Additionally, there have been no confirmed cases of human CCHFV infection reported from Nigeria.Principal FindingsSamples from sera (n = 1189) collected from four Local Government Areas in Borno State (Askira/Uba, Damboa, Jere and Maiduguri) were assessed for the presence of IgG and IgM antibodies. The positivity rates for IgG and IgM were 10.6% and 3.5%, respectively. Additionally, sera from undiagnosed febrile patients (n = 380) were assessed by RT-PCR assay for the presence of CCHFV RNA. One positive sample was characterised by further by next generation sequencing (NGS) resulting in complete S, M and L segment sequences.ConclusionsThis article provides evidence for the continued exposure of the human population of Nigeria to CCHFV. The genomic analysis provides the first published evidence of a human case of CCHFV in Nigeria and its phylogenetic context.

Phylogeny of tick-derived Crimean-Congo hemorrhagic fever virus strains in Iran

The presence of Crimean-Congo hemorrhagic fever virus (CCHFV) in Iran was assessed by collecting ticks from Golpayegan, Isfahan Province. Real time RT-PCR was used to detect the CCHFV RNA in the tick population and the origins of the viral sequences were determined. The CCHFV RNA was detected in 5.2% of 492 ticks collected from livestock in different regions of Golpayegan. The tick species that tested positive for the presence of CCHFV RNA included Hyalomma, Rhipicephalus and Haemaphysalis species. Phylogenetic analysis using the partial S-segment indicated that eight sequences clustered in clade IV (Asia-1) and three other sequences aligned within clade VI (Europe) with other CCHFV strains from Kosovo (Kosova1917) and Russia (Kashmanov).

Seroprevalence of Crimean-Congo Hemorrhagic Fever Virus in Erzincan Province, Turkey, Relationship with Geographic Features and Risk Factors.

To determine the seroprevalence and risk factors associated with Crimean-Congo hemorrhagic fever virus (CCHFV) in residents of Erzincan, Turkey. Although CCHFV is endemic in Erzincan, this is the first study to evaluate its seroprevalence in this region. This study included a total of 372 subjects, 174 of whom had been exposed to or bitten by ticks, 145 of whom worked with livestock, and 53 of whom resided in the city and did not have exposure to livestock. Data on CCHFV IgG and IgM antibodies were extracted from serum samples collected from all subjects using an ELISA. All samples were tested for CCHFV IgG and CCHFV IgM. Only IgM-positive samples were processed for detection of viral RNA through RT-PCR. Using seropositive cases only, we performed spatial analyses to evaluate correlations between seroprevalence and geographic location (i.e., proximity to rivers, altitude, and slope angle of land). In this study, 14.0% (52/322) of the total subjects were positive for CCHFV IgG. Seven of the individuals were positive both for CCHFV IgG and CCHFV IgM. Of these seven, only one sample tested positive for CCHFV RNA. Individuals who worked with livestock in the rural areas and had a history of tick exposure were statistically more likely to test positive for CCHFV IgG than individuals from the city and not exposed to ticks (p < 0.05). Seroprevalence was affected by geographic characteristics, including distance to rivers, altitude, and slope angle of land. We observed a high seroprevalence of CCHFV in Erzincan, which is similar to that observed in other endemic regions of Turkey. CCHFV seroprevalence rates are found to be quite high in the people who live in the sloping fields at certain heights and where there are a lot of rivers and streams.

RIG-I Mediates an Antiviral Response to Crimean-Congo Hemorrhagic Fever Virus.

In the cytoplasm, the retinoic acid-inducible gene I (RIG-I) senses the RNA genomes of several RNA viruses. RIG-I binds to viral RNA, eliciting an antiviral response via the cellular adaptor MAVS. Crimean-Congo hemorrhagic fever virus (CCHFV), a negative-sense RNA virus with a 5'-monophosphorylated genome, is a highly pathogenic zoonotic agent with significant public health implications. We found that, during CCHFV infection, RIG-I mediated a type I interferon (IFN) response via MAVS. Interfering with RIG-I signaling reduced IFN production and IFN-stimulated gene expression and increased viral replication. Immunostimulatory RNA was isolated from CCHFV-infected cells and from virion preparations, and RIG-I coimmunoprecipitation of infected cell lysates isolated immunostimulatory CCHFV RNA. This report serves as the first description of a pattern recognition receptor for CCHFV and highlights a critical signaling pathway in the antiviral response to CCHFV. CCHFV is a tick-borne virus with a significant public health impact. In order for cells to respond to virus infection, they must recognize the virus as foreign and initiate antiviral signaling. To date, the receptors involved in immune recognition of CCHFV are not known. Here, we investigate and identify RIG-I as a receptor involved in initiating an antiviral response to CCHFV. This receptor initially was not expected to play a role in CCHFV recognition because of characteristics of the viral genome. These findings are important in understanding the antiviral response to CCHFV and support continued investigation into the spectrum of potential viruses recognized by RIG-I.