Fatal Encephalitis Caused by Cristoli Virus, an Emerging Orthobunyavirus, France

Rodriguez, Christophe; Gricourt, Guillaume; N’Debi, Mélissa; Démontant, Vanessa; Poiteau, Lila; Burrel, Sonia; Boutolleau, David; Woerther, Paul‐Louis; Cálvez, Vincent; Ströer, Sébastian; Pawlotsky, Jean‐Michel

doi:10.3201/eid2606.191431

Cited by 27 publications

(15 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Relegated to research labs for many years, CSF mNGS testing is now clinically available (at the time of writing, UCSF Clinical Laboratory is the only provider of the assay for CSF in the United States, but other laboratories have assays at different stages of development, with Johns Hopkins Medicine soon to launch a clinical assay 15 ). Although not meant to be an exhaustive list, internationally, clinical CSF mNGS testing is available in the United Kingdom 74 , France 75 , South Korea 54 and China 76 , 77 . The validation data for the UCSF assay demonstrated that it had a sensitivity of 73–92% and a specificity of 96–99%, depending on the pathogen 16 .…”

Section: Clinical Evaluation and Adoptionmentioning

confidence: 99%

Metagenomics for neurological infections — expanding our imagination

2020

View full text Add to dashboard Cite

Section: Clinical Evaluation and Adoptionmentioning

confidence: 99%

Metagenomics for neurological infections — expanding our imagination

2020

View full text Add to dashboard Cite

“…These two separate arboviral mutations, each responsible for devastating epidemics of global impact, highlight the importance of expanding genomic epidemiology and surveillance of vector-borne pathogens. Furthermore, mNGS recently identified novel vector-borne pathogens including the tick-borne flaviviruses like Alongshan and highly fatal mosquito-borne orthobunyaviruses like Cristoli, Umbre, and others (39)(40)(41). These emerging pathogens were identified in high-resource areas where clinical staff had access to mNGS technology.…”

Section: Discussionmentioning

confidence: 99%

Discovering disease-causing pathogens in resource-scarce Southeast Asia using a global metagenomic pathogen monitoring system

Bohl

Lay

Chea

et al. 2021

Preprint

View full text Add to dashboard Cite

Understanding the regional pathogen landscape and surveillance of emerging pathogens is key to mitigating epidemics. Challenges lie in resource-scarce settings, where outbreaks are likely to emerge, but where laboratory diagnostics and bioinformatics capacity are limited. Using unbiased metagenomic next generation sequencing (mNGS), we identified a variety of vector-borne, zoonotic and emerging pathogens responsible for undifferentiated fevers in a peri-urban population in Cambodia. From March 2019 to October 2020, we enrolled 473 febrile patients aged 6 months to 65 years of age presenting to a large peri-urban hospital in Cambodia. We collected sera and prepared sequencing libraries from extracted pathogen RNA for unbiased metagenomic sequencing and subsequent bioinformatic analysis on the global cloud-based platform, IDseq. We employed multivariate Bayesian models to evaluate specific pathogen risk causing undifferentiated febrile illness. mNGS identified vector-borne pathogens as the largest clinical category with dengue virus (124/489) as the most abundant pathogen. Underappreciated zoonotic pathogens such as Plasmodium knowlesi, leptospirosis, and co-infecting HIV were also detected. Early detection of chikungunya virus presaged a larger national outbreak of more than 6,000 cases. Pathogen-agnostic mNGS investigation of febrile persons in resource-scarce Southeast Asia is feasible and revealing of a diverse pathogen landscape. Coordinated and ongoing unbiased mNGS pathogen surveillance can better identify the breadth of endemic, zoonotic or emerging pathogens and deployment of rapid public health response.

show abstract

“…Important human-infecting orthobunyaviruses include Oropouche, Jamestown Canyon and La Crosse (LACV) viruses, which are associated with acute febrile illnesses with frequent central nervous system infiltration; and Ngari virus, which is responsible for fatal hemorrhagic fever (4)(5)(6). Recent reports of the newly-identified Cristoli orthobunyavirus and the reemergence of Umbre orthobunyavirus as agents of fatal encephalitis, confirm the risk posed by orthobunyaviruses to human health (7,8). Whilst vaccines have been developed against several animal-infecting orthobunyaviruses, including SBV (2,9), no FDA-approved vaccines or therapies are available for those infecting humans.…”

Section: Introductionmentioning

confidence: 92%

The structure of a native orthobunyavirus ribonucleoprotein reveals a key role for viral RNA in maintaining its helical architecture

Hopkins

Álvarez‐Rodríguez

Heath

et al. 2021

Preprint

View full text Add to dashboard Cite

The Bunyavirales order of RNA viruses comprises emerging pathogens for which approved preventative or therapeutic measures for human use are not available. The genome of all Bunyavirales consists of negative-sense RNA segments wrapped by the virus-encoded nucleocapsid protein (NP) to form ribonucleoproteins (RNPs). RNPs represent the active template for RNA synthesis and the form in which the genome is packaged into virions, functions that require inherent flexibility. We present a pseudo-atomic model of a native RNP purified from Bunyamwera virus (BUNV), the prototypical Bunyavirales member, based on a cryo-electron microscopy (cryo-EM) average at 13 Å resolution with subsequent fitting of the BUNV NP crystal structure by molecular dynamics. We show the BUNV RNP possesses relaxed helical architecture, with successive helical turns separated by ∼18 Å. The model shows that adjacent NP monomers in the RNP chain interact laterally through flexible N- and C-terminal arms, with no helix-stabilizing interactions along the longitudinal axis. Instead, EM analysis of RNase-treated RNPs suggests their chain integrity is dependent on the encapsidated genomic RNA, thus providing the molecular basis for RNP flexibility. Overall, this work will assist in designing anti-viral compounds targeting the RNP and inform studies on bunyaviral RNP assembly, packaging and RNA replication.SignificanceBunyaviruses are emerging RNA viruses that cause significant disease and economic burden and for which vaccines or therapies approved for human use do not exist. The bunyavirus genome does not exist as naked RNA; instead it is wrapped up by the nucleoprotein (NP) to form a ribonucleoprotein (RNP). Using the prototypical bunyavirus, Bunyamwera virus, we determined the 3D structure of the native RNP, revealing a helical architecture with NP molecules linked by lateral contacts only, with no helix-stabilizing longitudinal contacts. Instead, the RNA genome itself plays a role in maintaining the helical architecture, allowing a high degree of flexibility that is critical for several stages of the virus replication cycle, such as segment circularization and genome packaging into virions.

show abstract

Fatal Encephalitis Caused by Cristoli Virus, an Emerging Orthobunyavirus, France

Cited by 27 publications

References 15 publications

Metagenomics for neurological infections — expanding our imagination

Metagenomics for neurological infections — expanding our imagination

Discovering disease-causing pathogens in resource-scarce Southeast Asia using a global metagenomic pathogen monitoring system

The structure of a native orthobunyavirus ribonucleoprotein reveals a key role for viral RNA in maintaining its helical architecture

Contact Info

Product

Resources

About