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Viral metagenomics revealed novel betatorquevirus species in pediatric inpatients with encephalitis/meningoencephalitis from Ghana.

ABSTRACT: The cause of acute encephalitis/meningoencephalitis in pediatric patients remains often unexplained despite extensive investigations for large panel of pathogens. To explore a possible viral implication, we investigated the virome of cerebrospinal fluid specimens of 70 febrile pediatric inpatients with clinical compatible encephalitis/meningoencephalitis. Using viral metagenomics, we detected and genetically characterized three novel human Torque teno mini virus (TTMV) species (TTMV-G1-3). Phylogenetically, TTMV-G1-3 clustered in three novel monophyletic lineages within genus Betatorquevirus of the Anelloviridae family. TTMV-G1-3 were highly prevalent in diseased children, but absent in the healthy cohort which may indicate an association of TTMV species with febrile illness. With 2/3 detected malaria co-infection, it remains unclear if these novel anellovirus species are causative agents or increase disease severity by interaction with malaria parasites. The presence of the viruses 28 days after initiating antimalarial and/or antibiotic treatment suggests a still active viral infection likely as effect of parasitic and/or bacterial co-infection that may have initiated a modulated immune system environment for viral replication or a defective virus clearance. This study increases the current knowledge on the genetic diversity of TTMV and strengthens that human anelloviruses can be considered as biomarkers for strong perturbations of the immune system in certain pathological conditions.

SUBMITTER: Eibach D

PROVIDER: S-EPMC6382885 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Viral metagenomics revealed novel betatorquevirus species in pediatric inpatients with encephalitis/meningoencephalitis from Ghana.

Eibach Daniel D Hogan Benedikt B Sarpong Nimako N Winter Doris D Struck Nicole S NS Adu-Sarkodie Yaw Y Owusu-Dabo Ellis E Schmidt-Chanasit Jonas J May Jürgen J Cadar Daniel D

Scientific reports 20190220 1

The cause of acute encephalitis/meningoencephalitis in pediatric patients remains often unexplained despite extensive investigations for large panel of pathogens. To explore a possible viral implication, we investigated the virome of cerebrospinal fluid specimens of 70 febrile pediatric inpatients with clinical compatible encephalitis/meningoencephalitis. Using viral metagenomics, we detected and genetically characterized three novel human Torque teno mini virus (TTMV) species (TTMV-G1-3). Phylo ...[more]

PMID: 30787417

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Project description:BackgroundRodents are widely distributed and are the natural reservoirs of a diverse group of zoonotic viruses. Thus, analyzing the viral diversity harbored by rodents could assist efforts to predict and reduce the risk of future emergence of zoonotic viral diseases. Rodents are commonly used in animal testing, particularly mice and rats. Experimental rats are important animal models, and a history of pathogenic infections in these animals will directly affect the animal trial results. The pathogenicity of Anellovirus (AV) remains poorly understood due to the lack of a suitable model cell line or animal to support the viral cycle. This study aimed to discover possible anelloviruses from the virome in feces of experimental rats by viral metagenomic technique.MethodsFecal samples were collected from 10 commercial SD rats and pooled into a sample pool and then subjected to libraries construction which was then sequenced on Illumina MiSeq platform. The sequenced reads were analyzed using viral metagenomic analysis pipeline and two novel anelloviruses (AVs) were identified from fecal sample of experimental rats. The prevalence of these two viruses was investigated by conventional PCR.ResultsThe complete genomic sequence of these two AVs were determined and fully characterized, with strain name ratane153-zj1 and ratane153-zj2. The circular genomes of ratane153-zj1 and ratane153-zj2 are 2785 nt and 1930 nt in length, respectively, and both include three ORFs. Ratane153-zj1 closely clustered with members within the genus Wawtorquevirus and formed a separate branch based on the phylogenetic tree constructed over the amino acid sequence of ORF1 of the two AVs identified in this study and other related AVs. While the complete amino acid sequences of ORF1 of ratane153-zj2 (nt 335 to 1390) had the highest sequence identity with an unclassified AV (GenBank No. ATY37438) from Chinchilla lanigera, and they clustered with one AV (GenBank No. QYD02305) belonging to the genus Etatorquevirus from Lynx rufus. Conventional PCR with two sets of specific primers designed based on the two genomes, respectively, showed that they were detectable at a low frequency in cohorts of experimental rats.ConclusionOur study expanded the genome diversity of AVs and provided genetic background information of viruses existed in experimental rats.

Project description:BackgroundDepending on geographic location, causes of encephalitis, meningoencephalitis and meningitis vary substantially. We aimed to identify the most frequent causes, clinical presentation and long-term outcome of encephalitis, meningoencephalitis and meningitis cases treated in the Inselspital University Hospital Bern, Switzerland.MethodsIn this monocentric, observational study, we performed a retrospective review of clinical patient records for all patients treated within a 3-year period. Patients were contacted for a telephone follow-up interview and to fill out questionnaires, especially related to disturbances of sleep and wakefulness.ResultsWe included 258 patients with the following conditions: encephalitis (18%), nonbacterial meningoencephalitis (42%), nonbacterial meningitis (27%) and bacterial meningoencephalitis/meningitis (13%). Herpes simplex virus (HSV) was the most common cause of encephalitis (18%); tick-borne encephalitis virus (TBEV) was the most common cause of nonbacterial meningoencephalitis (46%), enterovirus was the most common cause of nonbacterial meningitis (21%) and Streptococcus pneumoniae was the most common cause of bacterial meningoencephalitis/meningitis (49%). Overall, 35% patients remained without a known cause. After a median time of 16 months, 162 patients participated in the follow-up interview; 56% reported suffering from neurological long-term sequelae such as fatigue and/or excessive daytime sleepiness (34%), cognitive impairment and memory deficits (22%), headache (14%) and epileptic seizures (11%).ConclusionsIn the Bern region, Switzerland, TBEV was the overall most frequently detected infectious cause, with a clinical manifestation of meningoencephalitis in the majority of cases. Long-term neurological sequelae, most importantly cognitive impairment, fatigue and headache, were frequently self-reported not only in encephalitis and meningoencephalitis survivors but also in viral meningitis survivors up to 40 months after acute infection.

Dataset Information

Viral metagenomics revealed novel betatorquevirus species in pediatric inpatients with encephalitis/meningoencephalitis from Ghana.

Publications

Viral metagenomics revealed novel betatorquevirus species in pediatric inpatients with encephalitis/meningoencephalitis from Ghana.

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