Crimean–Congo haemorrhagic fever virus

Hawman, David W.; Feldmann, Heinz

doi:10.1038/s41579-023-00871-9

Cited by 77 publications

(97 citation statements)

References 183 publications

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“…Nairoviruses infect arthropods and can be transmitted to humans via tick bites (35). Some nairoviruses can cause disease in humans, but the Crimean-Congo Haemorrhagic Fever (CCHF) viruses are noteworthy for being highly pathogenic (36). Previously, EVEs similar to the nucleoprotein of nairoviruses had been described in the genome of the black-legged tick Ixodes scapularis (1).…”

Section: Resultsmentioning

confidence: 99%

Deep-mining of vertebrate genomes reveals an unexpected diversity of endogenous viral elements

Barreat,

Katzourakis

2023

Preprint

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Endogenous viral elements (EVEs) are key to our understanding of the diversity, host range and evolutionary history of viruses. Given the increasing amounts of virus and host sequence data, a systematic search for EVEs is becoming computationally challenging. We used ElasticBLAST on the Google Cloud Platform to perform a comprehensive search for EVEs (kingdomsShotokuviraeandOrthornavirae) across vertebrates. We provide evidence for the first EVEs belonging to the familiesChuviridae,Paramyxoviridae,NairoviridaeandBenyviridaein vertebrate genomes. We also find an EVE from the Hepacivirus genus of flaviviruses with orthology across murine rodents. Phylogenetic analysis of hits closely related to reptarenavirus and filovirus ectodomains suggest three independent captures from a retroviral source. Our findings increase the family-level diversity of non-retroviral EVEs in vertebrates by 44%. In particular, our results shed light on key aspects of the natural history and evolution of viruses in the phylaNegarnaviricotaandKitrinoviricota.

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Section: Resultsmentioning

confidence: 99%

Deep-mining of vertebrate genomes reveals an unexpected diversity of endogenous viral elements

Barreat,

Katzourakis

2023

Preprint

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“…Virus replication occurs in the cytoplasm of infected cells, and the virus particles mature by budding at the membranes of the Golgi apparatus. The viruses of this family recognize a wide variety of hosts, including humans, in which they can cause severe disease, such as that caused by Crimean-Congo hemorrhagic fever virus (CCHFV) (Hawman and Feldmann, 2023). They are increasingly considered a threat to human health and are relevant examples of emerging viral infections.…”

Section: Introductionmentioning

confidence: 99%

Do NSm virulence factors in the Bunyavirales viral order originate from Gn gene duplication?

Lefebvre

Lin

Cole

et al. 2023

Preprint

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Several viral members of the large viral order of the Bunyavirales carry a NSm protein that acts as a virulence factor. Here we used AlphaFold to predict the structures of these NSm proteins and surprisingly found that the cytosolic domain of the Nairoviridae family NSm (NSmcyto) is predicted to have a very similar fold to the cytosolic domain of glycoprotein N (Gncyto). This observation is particularly striking for CCHFV (a member of the Nairoviridae family), for which the NMR structure of the Gncyto domain has already been described in the literature and shows a double zinc finger. We show that while the sequence identity between the NSmcyto and Gncyto domains is generally weak, the strict conservation of the two zinc-finger forming CCCH motifs in CCHFV NSmcyto explains the full structural conservation predicted by AlphaFold. Interestingly, a similar observation is made for the predictions of NSm in another group of the order Bunyavirales, the family Peribunyaviridae, where the Gncyto structures have not yet been described experimentally. Our findings suggest that NSm is the result of a gene duplication event in these viruses, and indicate that such events may indeed be common in the recent evolutionary history of RNA viruses. Importantly, our predictions provide a first insight into the long-unknown structure of NSm and its link to virulence.

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“…It is reported that the disease is endemic in Africa, Asia, Southeast Europe, and the Middle East, but sporadic cases have been reported in different parts of the world. Massive bleeding and low platelet count are life‐threatening findings of the disease 8 . The absence of a proven vaccine or antiviral therapy poses significant challenges in managing CCHF.…”

Section: Introductionmentioning

confidence: 99%

“…Increasing clinical and laboratory evidence underscores the significant link between markedly elevated levels of proinflammatory cytokines, especially IL‐6, and the outlook and survival rates of patients with CCHF. This emphasizes the crucial role of ILs in assessing the prognosis and mortality risk in CCHF cases 8–10 Concurrently, there is an increasing body of literature highlighting the role of the IL‐36 family in the proinflammatory pathway 11 . Notably, IL‐36 and IL‐36 receptor (IL‐36R) antagonists have emerged as important therapeutic targets for treating inflammatory conditions 12–15 .…”

Section: Introductionmentioning

confidence: 99%

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IL‐36 signaling pathway dysregulation in Crimean–Congo hemorrhagic fever virus patients: A potential therapeutic avenue

Doğan,

Büyüktuna

2023

Journal of Medical Virology

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Crimean–Congo hemorrhagic fever (CCHF) is a severe viral disease. The scientific literature is growing, emphasizing the significance of the interleukin (IL)‐36 family in the proinflammatory signaling pathway. However, to date, no research has explored the potential of IL‐36 family members as biomarkers in CCHF. This study aims to bridge this gap by evaluating IL‐36α, IL‐36β, and IL‐36γ levels in CCHF patients and healthy controls and investigating their association with disease severity and prognosis. Sixty confirmed CCHF patients and 29 healthy controls were enrolled in this case‐control study. Serum levels of IL‐36α, IL‐36β, and IL‐36γ were measured using enzyme‐linked immunosorbent assays. Significantly higher levels of IL‐36α and IL‐36β were observed in CCHF patients compared to healthy controls (p < 0.05). However, no statistically significant changes were found in IL‐36γ levels between the two groups. Among the CCHF patients, those who did not survive exhibited significantly elevated IL‐36α and IL‐36γ levels compared to survivors (p < 0.01). Positive correlations were identified between IL‐36α and IL‐36γ levels with activated partial thromboplastin time, and D‐dimer (p < 0.01). Conversely, platelet levels showed a negative correlation with IL‐36α and IL‐36γ levels (p < 0.01). The increased levels of IL‐36α, IL‐36β, and IL‐36γ in patients indicate their participation in proinflammatory reactions in CCHF patients. Understanding the role of IL‐36 family members in CCHF pathogenesis could offer valuable insights into disease progression and facilitate the development of targeted therapeutic strategies.

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Crimean–Congo haemorrhagic fever virus

Cited by 77 publications

References 183 publications

Deep-mining of vertebrate genomes reveals an unexpected diversity of endogenous viral elements

Deep-mining of vertebrate genomes reveals an unexpected diversity of endogenous viral elements

Do NSm virulence factors in the Bunyavirales viral order originate from Gn gene duplication?

IL‐36 signaling pathway dysregulation in Crimean–Congo hemorrhagic fever virus patients: A potential therapeutic avenue

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