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Identification of a new cyclovirus in cerebrospinal fluid of patients with acute central nervous system infections.

ABSTRACT: Acute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology remains unknown in a large proportion of cases. We identified and characterized the full genome of a novel cyclovirus (tentatively named cyclovirus-Vietnam [CyCV-VN]) in cerebrospinal fluid (CSF) specimens of two Vietnamese patients with CNS infections of unknown etiology. CyCV-VN was subsequently detected in 4% of 642 CSF specimens from Vietnamese patients with suspected CNS infections and none of 122 CSFs from patients with noninfectious neurological disorders. Detection rates were similar in patients with CNS infections of unknown etiology and those in whom other pathogens were detected. A similar detection rate in feces from healthy children suggested food-borne or orofecal transmission routes, while high detection rates in feces from pigs and poultry (average, 58%) suggested the existence of animal reservoirs for such transmission. Further research is needed to address the epidemiology and pathogenicity of this novel, potentially zoonotic virus.

SUBMITTER: Tan le V

PROVIDER: S-EPMC3684831 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Identification of a new cyclovirus in cerebrospinal fluid of patients with acute central nervous system infections.

Tan Le Van le V van Doorn H Rogier HR Nghia Ho Dang Trung HD Chau Tran Thi Hong TT Tu Le Thi Phuong le TP de Vries Michel M Canuti Marta M Deijs Martin M Jebbink Maarten F MF Baker Stephen S Bryant Juliet E JE Tham Nguyen Thi NT BKrong Nguyen Thi Thuy Chinh NT Boni Maciej F MF Loi Tran Quoc TQ Phuong Le Thi le T Verhoeven Joost T P JT Crusat Martin M Jeeninga Rienk E RE Schultsz Constance C Chau Nguyen Van Vinh NV Hien Tran Tinh TT van der Hoek Lia L Farrar Jeremy J de Jong Menno D MD

mBio 20130618 3

Acute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology remains unknown in a large proportion of cases. We identified and characterized the full genome of a novel cyclovirus (tentatively named cyclovirus-Vietnam [CyCV-VN]) in cerebrospinal fluid (CSF) specimens of two Vietnamese patients with CNS infections of unknown etiology. CyCV-VN was subsequently detected in 4% of 642 CSF specimens from Vietnamese patients with suspected CNS infections and ...[more]

PMID: 23781068

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Project description:BACKGROUND:The host response to intruders in the central nervous system (CNS) may be beneficial but could also be harmful and responsible for neurologic symptoms and sequelae in CNS infections. This immune response induces the activation of the kynurenine pathway (KP) with the production of neuroactive metabolites. Herein, we explored cytokine and KP responses in cerebrospinal fluid (CSF) and serum in patients with encephalitis, aseptic, and bacterial meningitis. METHODS:Cytokines were measured in CSF and serum by multiplex assay in adult patients with encephalitis of infectious, autoimmune or unknown etiology (n?=?10), aseptic meningitis (ASM, n?=?25), acute bacterial meningitis (ABM, n?=?6), and disease control patients with similar symptoms but without pleocytosis in CSF (n?=?42). Liquid chromatography-tandem mass spectrometry (LC-MS/ MS) was used to measure KP metabolites in CSF and serum. RESULTS:A characteristic pattern of increasing cytokine levels and KP metabolites was found in CSF from encephalitis to ASM, with the highest levels in ABM. In ASM and ABM, most inflammatory mediators, including IL-6, IL-8, and IFN-inducible protein-10 (IP-10), showed markedly elevated levels in CSF compared with serum, indicating production within the CNS. In contrast to most mediators, the highest level of IP-10 was found in the ASM group, suggesting a potential role for IP-10 in aseptic/viral meningitis. Neopterin and IP-10 were associated with marked changes in KP metabolites in CSF with increasing kynurenine/tryptophan ratio reflecting indoleamine 2,3-dioxygenase activity. Neopterin, a marker of IFN-? activity, was associated with an unfavorable balance between neuroprotective and neurotoxic tryptophan metabolites. CONCLUSION:We show that parenchymal and meningeal inflammations in CNS share a characteristic cytokine profile with a general immune response in the CSF with limited influence from the systemic circulation. IFN-? activity, assessed by neopterin and IP-10 levels, may play a role in the activation of the KP pathway in these patients, potentially mediating neurotoxic effects.

Dataset Information

Identification of a new cyclovirus in cerebrospinal fluid of patients with acute central nervous system infections.

Publications

Identification of a new cyclovirus in cerebrospinal fluid of patients with acute central nervous system infections.

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