Search Results (87)

Background: Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne viral disease with a high fatality rate, and no licensed vaccines are currently available. The nucleoprotein (NP) of the Crimean-Congo hemorrhagic fever virus (CCHFV) plays a critical role in viral replication and immune recognition, making it a promising target for vaccine development. This study aimed to design and evaluate a multiepitope recombinant DNA vaccine targeting the NP of CCHFV. Methods: Cytotoxic T lymphocyte (CTL) epitopes from the NP were predicted via immunoinformatics approaches and systematically assessed for antigenicity, allergenicity, toxicity, hydrophobicity, and global population coverage. The selected epitopes were incorporated into four DNA vaccine constructs driven by a cytomegalovirus promoter, adjuvanted with human β-defensin 3 (hBD3), and fused to the reporter protein mRuby3. The constructs were evaluated in vitro using a fluorescent reporter system designed to provide a readout of TCR signaling upon the co-culture of T lymphocytes with differentiated monocytic cells expressing antigens. In vivo immunogenicity and protective efficacy were assessed in BALB/c (exploratory pilot) and IFNAR^−/− mice, a highly susceptible model for viral infection. Cytokine responses were measured to assess immunogenicity. Results: In vitro assays showed predominantly antigen-independent T-cell activation, suggesting that nonspecific stimulation inherent to the reporter co-culture system likely obscured the detection of antigen-specific TCR signaling. In vivo analyses in BALB/c mice revealed that the constructs elicited only modest systemic cytokine profiles while CCHFV-specific IgG and IFN-γ secretion remained undetectable, indicating that antigen-specific T-cell and antibody responses were limited. In the IFNAR^−/− challenge model, several peptide groups achieved significant 2–3 log reductions in tissue viral RNA and infectious titers (p < 0.05 vs. sham). However, the observed viral modulations were insufficient to reach the protective threshold and did not translate to a survival benefit (0%). Conclusion: Despite a rational in silico foundation, the multiepitope DNA vaccine constructs demonstrated limitations in inducing potent, antigen-specific immunity across both mouse models. The lack of antigen-specific responses indicates limitations in epitope selection, construct design, and delivery strategies, requiring optimization of next-generation epitope-based vaccines. These findings highlight the complexity of translating computational epitope predictions into functional vaccines, and provide benchmark data as a framework to guide future optimizations. Full article

Crimean-Congo hemorrhagic fever virus (CCHFV) is transmitted predominantly through the bite of infected Hyalomma ticks, yet the earliest events at the vector–host–virus interface in human skin remain largely undefined. This review synthesizes current knowledge of human cutaneous structure and immunity, tick feeding biology, and salivary immunomodulation to propose how local skin responses may shape systemic outcomes of CCHFV disease. We detail the roles and permissiveness of major skin-resident and infiltrating cell types, including keratinocytes, melanocytes, Langerhans cells, dermal dendritic cells, monocytes/macrophages, fibroblasts, granulocytes, T cells, B cells, NK cells, and innate lymphoid cells, in antiviral defense and as potential early targets or carriers of CCHFV. Emphasis is placed on how tick saliva components reprogram the cutaneous microenvironment, alter interferon, complement, inflammasome, and cytokine pathways, and may enable saliva-assisted transmission and viral dissemination from the dermis. We highlight mounting evidence from other arboviruses demonstrating that the skin can act as both a barrier and a major amplifying organ, and we extrapolate testable hypotheses on how early cutaneous immune dynamics might influence CCHFV severity and hemorrhagic manifestations. Finally, we outline key knowledge gaps that, if answered, may inform the development of vaccines and therapeutics that harness cutaneous immunity to block systemic spread. Full article

Rift Valley fever virus (RVFV) and Crimean-Congo hemorrhagic fever virus (CCHFV) are designated by the World Health Organization as priority pathogens due to their epidemic potential, zoonotic transmission, and the absence of licensed therapeutics or vaccines. The development of effective antivirals critically relies on robust in vitro and in vivo models; however, progress is limited by the requirement for high-containment facilities. In this review, we provide a comprehensive overview of the experimental models currently available for RVFV and CCHFV, ranging from cell-based assays to animal models, and discuss their respective advantages, limitations, and translational relevance. We further highlight strategies allowing for BSL-2 experimentations, thereby expanding research accessibility, and accelerating the development of countermeasures against these high-priority pathogens. Full article

Crimean–Congo Hemorrhagic Fever (CCHF) disease, caused by the CCHF virus (CCHFV), poses a significant fatality risk whose underlying pathological mechanisms, including the contribution of coagulation factors, imbalances and platelet abnormalities, remain poorly understood. Here we present a meta-analysis and meta-regression analysis using clinical data from coagulation assays and platelet parameters as predictive disease indices with the goal of uncovering pathognomonic factors and to pave a way for the development of effective therapeutic approaches. Methods: We systematically analyzed published studies reporting coagulation assays and platelet indices in patients with confirmed CCHF. Data from 1779 patients across the published studies were analyzed to assess associations between laboratory parameters and the fatality risk, while evaluating heterogeneity and prognostic significance. Results: Fatal outcomes were strongly associated with elevated liver enzymes (AST: 1116.71 ± 1454.08 IU/mL; ALT: 446.56 ± 457.41 IU/mL) and prolonged clotting times (PT: 19.53 ± 6.57 s; aPTT: 64.02 ± 23.13 s; INR: 1.53 ± 0.56). D-dimer levels did not significantly predict fatality. Thrombocytopenia and coagulopathy emerged as independent risk factors for adverse outcomes. Notably, protein C and protein S levels did not differ between survivors and non-survivors, suggesting that the coagulopathy is not purely consumptive or a result of impaired hepatic synthesis. In contrast, mildly reduced antithrombin levels (83.65 ± 19.90) were weighted toward increased mortality. Full article

Tick-borne viruses (TBVs) pose significant public health and economic threats. Pakistan has endemic Crimean-Congo hemorrhagic fever virus (CCHFV), but evidence suggests broader TBV circulation. This study assessed the seroprevalence of thirteen TBVs (seven are members of the genus Orthonairovirus and six are members of the genus Bandavirus) in humans, livestock, and rats in Punjab, Pakistan. Serum samples (n = 794: 321 livestock, 253 human, and 220 rat) were collected from the Narowal, Lahore, and Faisalabad districts. Antibodies to viral NPs were detected using the luciferase immunoprecipitation system (LIPS). The overall seroprevalence was 19.14% (152/794); it was highest in livestock (27.10%), then humans (20.55%), and then rats (5.91%). The highest seroprevalence rates were 3.12% for CCHFV in livestock, 3.56% for Yezo virus (YEZV) in humans, and 0.91% for Tamdy virus (TAMV) and Tacheng tick virus 1 (TcTV-1) in rats. Neutralizing antibodies were detected against CCHFV (1 cattle, 4 humans), Bhanja virus (BHAV) (3 livestock, 1 rat), TAMV (1 cattle), Guertu virus (GTV) (1 cattle), and Dabie bandavirus (2 cattle). Sixteen samples showed antibodies to both orthonairoviruses and bandaviruses, indicating co-exposure. Further analysis showed that seropositivity was not randomly distributed. Livestock kept in commercial farming systems and people working mainly outdoors had distinctly higher exposure to TBVs than subsistence livestock and indoor workers. The results supported the circulation of TBVs among hosts within the close socio-economic/ecological integration area of Pakistan. These findings confirm the circulation of CCHFV, SFTSV, GTV, and TAMV; provide the first serologic evidence of BHAV in Pakistan; and underscore the need for further investigation into the potential circulation of additional TBVs. All results demonstrated that multiple TBVs have been circulating among humans, livestock, and rodents in Pakistan. Full article

Apart from some information on dengue virus (DENV), there is limited data on the circulation of arboviruses in Burkina Faso. The aim of this study was to investigate antibody prevalence against six arboviruses in four regions of the country to document previous virus exposure. Serum samples collected between August 2018 and December 2022 from people infected with viral hepatitis B and C in Bobo-Dioulasso were used to detect IgG antibodies against DENV, Chikungunya virus (CHIKV), Zika virus (ZIKV), Yellow fever virus (YFV), Rift Valley fever virus (RVFV) and Crimean-Congo hemorrhagic fever virus (CCHFV) using commercial ELISA kits. A total of 1808 serum samples, accompanied by basic epidemiologic data (sex, age and residency) were included in this study. We observed an IgG antibodies seroprevalence of 75.4% for DENV, 30.8% for CHIKV, 2.9% for ZIKV, 1.2% for RVFV, 1.1% for CCHFV and 1.1% for YFV. Age, sex, and place of residence were significantly associated with seropositivity for DENV and age and sex with CHIKV seropositivity. The results suggested widespread circulation of DENV and CHIKV and possible circulation of CCHFV and RVFV in humans in Burkina Faso. The importance of strengthening arbovirus surveillance by including additional arboviruses in the diagnostic panel is emphasized. Full article

Crimean-Congo hemorrhagic fever (CCHF) and Rift Valley fever (RVF) are major zoonotic diseases, spread by arthropods, with livestock serving as amplifying hosts. Despite Nigeria’s large ruminant population and robust cross-border animal trade, data on the seroprevalence of the viral agents causing these diseases remain limited. A longitudinal serological survey was conducted in five major livestock markets across Nigeria. A total of 3450 animals (cattle, sheep, and goats) were tested for Crimean-Congo hemorrhagic fever virus (CCHFV) and Rift Valley fever virus (RVFV) antibodies using ELISA. Data on species, age, sex, animal origin, and tick infestation were collected and analyzed. Overall seroprevalence was 27.1% (95% CI: 25.6–28.6) for CCHFV and 5.8% (95% CI: 5.1–6.7) for RVFV. Cattle showed the highest prevalence for both CCHFV (55.4%) and RVFV (11.2%), followed by sheep (17.4% and 2.9%) and goats (8.6% and 3.4%). Evidence of mixed exposure to both CCHFV and RVFV antibodies was detected in 8.2% of cattle, 0.7% of sheep, and 0.2% of goats. Seropositivity was higher in older animals, females, tick-infested animals, and those of Nigerian origin compared to imported animals. Market-level variation was observed, with Mubi livestock market showing the highest CCHFV prevalence (35.5%) and Illela livestock market the highest RVF prevalence (11.2%). The detection of con-current CCHFV and RVFV antibodies, alongside high CCHFV prevalence and detectable RVFV circulation among Nigerian livestock highlight the risk of zoonotic spillover, particularly in livestock markets with intense human–animal interaction. Full article

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne zoonotic pathogen of growing public health concern in southeastern Europe. This study provides the first serological evidence of CCHFV circulation in Croatia, based on testing 1473 serum samples from farm and companion animals, including sheep, horses, cattle, goats, dogs, and cats. A total of 109 samples (7.4%) tested positive for CCHFV antibodies using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. The highest seroprevalence was recorded in sheep (28.3%), followed by horses (4.3%) and a single cat (0.5%), with no antibodies detected in cattle, goats, or dogs. Almost all seropositive animals originated from coastal and subcoastal Croatia, where Hyalomma ticks are present. Only two seropositive cases were detected in continental areas. Sheep samples from several farms in Zadar County showed intra-farm seropositivity rates of up to 85.7%, suggesting localised virus circulation likely influenced by vector distribution and farm-level practices. No viral ribonucleic acid (RNA) was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR), consistent with the transient nature of viremia in most animal hosts. These findings confirm the silent circulation of CCHFV in Croatia and reinforce the need for targeted, regionally adapted surveillance strategies that integrate multiple hosts and support early warning systems aligned with the One Health concept. Full article

Ticks from the Hyalomma genus have recently garnered public attention in countries in Northern and Central Europe, as they are transported by migratory birds and might have established stable populations due to climate warming. The main threat associated with Hyalomma ticks is their ability to transmit Crimean–Congo hemorrhagic fever virus (CCHFV), which can be fatal in up to 40% of cases. Here, we collected Hyalomma ticks from migratory birds during annual ringing actions in the spring seasons of 2023 and 2024. Four ticks were found on birds from the Acrocephalus genus and two on Hippolais icterina. The ticks were examined for the presence of Rickettsia spp., Babesia microti, Babesia divergens, Coxiella burnetii, Borreliella burgdorferi (s. l.), Anaplasma phagocytophilum, West Nile virus, and CCHF virus (CCHFV). The collected H. rufipes specimens were negative for tested pathogens, except for two ticks collected in 2024, which were positive for Rickettsia aeschlimannii. The data show that Hyalomma ticks are efficiently transported on birds preferring reedbeds or deciduous trees. The possibility of the occurrence of CCHF or rickettsiosis (induced by R. aeschlimannii) is currently assessed as low. Nevertheless, we have shown the transfer of Hyalomma ticks to Poland and indicated the need for careful future epidemiological monitoring of the presence of Hyalomma ticks. Full article

Crimean–Congo hemorrhagic fever virus (CCHF-V) and Ebola virus are lethal pathogens that cause widespread outbreaks of hemorrhagic fever. Both diseases can be transmitted through contact with the bodily fluids of infected individuals, but as an arbovirus, CCHF-V is primarily transmitted through tick bites. Both of these viruses are classified as Risk Group 4 due to the appreciable health threat they pose. To date, there are few effective treatments available to combat these deadly hemorrhagic fevers. Consequently, identifying and characterizing ion channels (viroporins) encoded in the viral genomes may lead to potential targeted drug development. Therefore, using bacteria-based genetic assays, two viroporin candidates from CCHF-V and Ebola have been examined, and their proposed structures have been modeled to aid in further drug discovery. The results indicate that CCHF-V-gp exhibits channel activity, which is indistinguishable from established viroporins found in other viruses. In contrast, our experimental approach was unable to uncover a viroporin candidate in the Ebola virus. Full article

Crimean–Congo hemorrhagic fever (CCHF) is a zoonotic viral disease endemic to parts of Africa, Asia and southeastern Europe. Bulgaria is one of the few European countries with the consistent annual reporting of human CCHF cases. This study provides a descriptive overview of 24 confirmed CCHF cases in Bulgaria between 2015 and 2024. Laboratory confirmation was performed by an enzyme-linked immunosorbent assay (ELISA) and/or real-time reverse transcriptase polymerase chain reaction (RT-qPCR) testing. Common findings included fever, fatigue, gastrointestinal symptoms, thrombocytopenia, leukopenia, liver dysfunction and coagulopathy. Two fatal cases were recorded. Two samples collected in 2016 and 2024 were subjected to whole-genome sequencing. Phylogenetic analysis showed that both strains clustered within the Turkish branch of the Europe 1 genotype and shared high genetic similarity with previous Bulgarian strains, as well as strains from neighboring countries. These findings suggest the long-term persistence of a genetically stable viral lineage in the region. Continuous molecular and clinical surveillance is necessary to monitor the evolution and public health impact of CCHFV in endemic areas. Full article

The recent discovery of Orthonairovirus songlingense (SGLV) and Norwavirus beijiense (BJNV) in China has raised significant concern due to their potential to cause severe human disease. However, little is known about the structural features and function of their nucleoproteins, which play a key role in the viral life cycle. By combining small-angle X-ray scattering (SAXS) data and AlphaFold 3 simulations, we reconstructed the BJNV and SGLV nucleoprotein structures for the first time. The SGLV and BJNV nucleoproteins have structures that are broadly similar to those of Orthonairovirus haemorrhagiae (CCHFV) nucleoproteins despite low sequence similarity. Based on structural analysis, several residues located in the positively charged region of BJNV and SGLV nucleoproteins have been indicated to be important for viral RNA binding. A positively charged RNA-binding crevice runs along the interior of the SGLV and BJNV ribonucleoprotein complex (RNP), shielding the viral RNA. Despite the high structural similarity between SGLV and BJNV nucleoprotein monomers, their RNPs adopt distinct conformations. These findings provide important insights into the molecular mechanisms of viral genome packaging and replication in these emerging pathogens. Also, our work demonstrates that experimental SAXS data can validate and improve predicted AlphaFold 3 structures to reflect their solution structure and also provides the first low-resolution structures of the BJNV and SGLV nucleoproteins for the future development of POC tests, vaccines, and antiviral drugs. Full article

This study aimed to assess the emergence and/or re-emergence of Tick-borne Diseases (TBD) in Portugal by linking the hemoparasite burden in companion animals to vector-borne disease dynamics through a One Health approach. Between 2015 and 2024, 1169 clinically suspected animals with hemoparasite infections, treated at the Hospital Veterinário de Santarém (HVS), underwent serological confirmation for Rickettsia conorii, Babesia canis, Ehrlichia spp., and Haemobartonella spp. A total of 3791 serological tests (3.2 tests per animal) were performed and 437 animals tested positive for at least one of the four hemoparasites under investigation. From 2020 to 2024, tests nearly tripled from 894 to 2883, raising positive cases and prevalence from 29.5% to 39.9%, especially for rickettsiosis and hemobartonellosis, indicating an increased circulation of their vectors. A national vector surveillance initiative identified Hyalomma spp., Rhipicephalus sanguineus, Ixodes ricinus, and Dermacentor sp. as primary tick vectors in Portugal for the hemoparasites mentioned above and for other agents like arbovirus, such as Crimean-Congo Hemorrhagic Fever Virus (CCHFV) and tick-borne encephalitis virus (TBEV). This study found that the vectors responsible for transmitting hemoparasitosis, given the high number of serologically positive cases detected in the HVS, represent an increasing risk for TBD. These findings highlight the relevance of companion animal monitoring as an early-warning component within a One Health surveillance approach. Full article

The Crimean–Congo hemorrhagic fever virus (CCHFV) is a single-stranded, segmented RNA virus belonging to the Nairoviridae family, and it is rapidly expanding across Africa, Asia, and southern Europe, probably favored by climate change and livestock trade. Its fatality rate in humans reaches up to 40%, and there is currently no specific treatment or vaccine available. Therefore, the development of therapies against CCHFV is essential, and their design requires understanding of the molecular evolution and genetic distribution of the virus. Motivated by these concerns, we present a comprehensive review of the molecular evolution, genetic characterization, and phylogeography of CCHFV, and we discuss their potential implications for therapeutic design. Specifically, we describe the virus’s capacity to increase its genetic diversity through numerous mutations, recombination events, and genomic reassortments, which affect fundamental viral functions such as RNA binding, host–virus interactions, viral entry, and polymerase activity. We also assess the presence of temporal heterogeneous rates of evolution and molecular adaptation among CCHFV coding regions, where purifying selection is generally predominant but diversifying selection is observed in molecular regions associated with host adaptation and transmission. We emphasize the importance of understanding the complex molecular evolution of CCHFV for the rational design of therapies and highlight the need for efforts in surveillance, evolutionary prediction, and therapeutic development. Full article

Tick-borne viruses (TBVs), notably Orthonairovirus haemorrhagiae (Crimean–Congo hemorrhagic fever virus, CCHFV), are emerging global health threats intensified by climate change. Rising temperatures and altered precipitation patterns are expanding the habitats of key tick vectors, increasing their survival and reproductive success. The African continent is characterized by many different climatic zones, and climatic shifts have increased or changed CCHFV transmission patterns, becoming greater risk to humans and livestock. Beyond Africa, CCHFV spread in Europe, the Middle East, and Asia and has been facilitated by factors such as livestock movement, deforestation, and migratory birds. Climate-driven shifts in tick seasonality, behavior, and vector competence may further enhance viral transmission. Addressing these challenges requires integrated responses, including enhanced surveillance, predictive modeling, and climate-adaptive vector control strategies. A One Health approach—linking environmental, animal, and human health domains—is essential. Innovative strategies such as anti-tick vaccines and sustainable vector control methods offer promise in reducing the burden of these diseases. Proactive, collaborative efforts at regional and international levels are crucial in tackling this growing public health challenge. Full article