Identification of a New Cyclovirus in Cerebrospinal Fluid of Patients with Acute Central Nervous System Infections

Le Van Tan,Tran Quoc Loi,Le Thi Phuong Tu,Le Thi Phuong,Constance Schultsz,Menno D De Jong,Marta Canuti,Tran Thi Hong Chau,Lia Van Der Hoek,Jeremy Farrar,Joost T P Verhoeven,Martin Deijs,Stephen Baker,Maciej F Boni,Juliet E Bryant,Maarten F Jebbink,H Rogier Van Doorn,Ho Dang Trung Nghia,Rienk E Jeeninga,Nguyễn Văn Vĩnh Châu ,Nguyen Thi Thuy Chinh B’krong ,Martín Crusat ,Michèl De Vries ,Nguyễn Thị Thắm

doi:10.1128/mbio.00231-13

Abstract

ABSTRACTAcute 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.

Highlights

IMPORTANCE Acute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology frequently remains unknown, which hampers development of therapeutic or preventive strategies
We identified and characterized the full genome of a novel cyclovirus in cerebrospinal fluid (CSF) specimens from two Vietnamese patients with CNS infections of unknown etiology, which was subsequently detected in none of 122 CSF specimens from patients with noninfectious neurological disorders but 4% of 642 CSF specimens from Vietnamese patients with suspected or confirmed CNS infections
The analysis of the CSF specimens generated 321,000 reads, which were reduced to 161,000 sequence reads for further analysis after excluding Escherichia coli-like sequences suspected to be derived from virus discovery assay (VIDISCA)-454 (454: Roche 454 Genome Sequencer FLX System) reagents

Summary

Introduction

IMPORTANCE Acute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology frequently remains unknown, which hampers development of therapeutic or preventive strategies. The identification of previously unknown pathogens in patients with acute CNS infections remains essential to improve prevention and clinical management of this frequently devastating syndrome. The discovery of such novel pathogens is facilitated by the availability of sensitive sequenceindependent molecular methods. Using a combination of an amplified fragment length polymorphism (AFLP)-based virus discovery assay (VIDISCA) and next-generation sequencing [2], we set out to look for nucleic acid sequences of potential novel pathogens in cerebrospinal fluid (CSF) specimens from Vietnamese adults and children with acute CNS infections of unknown etiology. We report the results of initial studies to explore the pathogenic potential of this virus in humans as well as the existence of possible animal reservoirs for zoonotic transmission

Methods

Results

Conclusion