Project

Discipline

séquençage à haut-débit; Identification de nouveau virus; Entérovirus; Infection du SNC; Infection du tractus respiratoire

Lead
Les infections du système nerveux central et du tractus respiratoire sont souvent considérées comme étant d’origines virales bien que l'identification de l’agent infectieux échoue fréquemment. Notre étude consiste à utiliser l’expertise de différents groupes ainsi que des opportunités offertes par notre plateforme de virologie clinique afin 1) Identifier la cause d’infections inexpliquées bien que présumées d’origines virales 2) Caractériser la cinétique des infections à entérovirus.
Lay summary
Au niveau du système nerveux central (SNC), comme mentionné ci-dessus, notre étude s’intéressera à identifier de nouveaux virus ou variants neurotropes sur la base d’analyses d’échantillons cliniques collectés chez des patients pour lesquels une encéphalite et/ou méningite est cliniquement avérée mais reste d’étiologie inconnue alors que l’ensemble des paramètres cliniques parlent en faveur d’une infection virale. Nous nous centrerons également sur des questions microbiologiques relatives à la pathogenèse et au diagnostic des infections à entérovirus, considérées comme représentant la cause la plus fréquente des infections du SNC. Au niveau du tractus respiratoire, nous analyserons des échantillons cliniques provenant de patients transplantés pulmonaire et d’enfants africains pour lesquels une infection respiratoire aigüe d’origine inconnue est documentée. Ces deux cohortes de patients ont été inclues dans de précédentes études effectuées par notre groupe et sélectionnés sur la base de leurs symptômes et facteurs de risques spécifiques associés. Bien que la présence d’une infection virale soit hautement suspectée pour ces patients, les analyses moléculaires permettant la détection de l’ensemble des virus respiratoires connus à ce jour restent négatives. Au niveau microbiologique, nous utiliserons la technologie de séquençage à haut-débit (NGS) pour rechercher de nouveaux virus ou variants. Un des objectifs de cette étude est d’établir un lien direct entre la technologie NGS et son application à des investigations spécifiques en virologie clinique. Cet aspect pourra être évalué grâce à notre accès privilégié à des prélèvements cliniques relevant et rigoureusement sélectionnés provenant de patients hospitalisés et/ou inclus dans des cohortes spécifiques.

Direct link to Lay Summary

Last update: 25.04.2013

Number	Title	Start	Funding scheme

Nucleic acid-based identification of viruses has changed the face of clinical virology during the last decade. Screening for common viral infections by polymerase chain reaction (PCR) or reverse transcription (RT-PCR) is performed on a daily basis and, if needed, viral loads can be quantified. Although a specific virus can be targeted individually, it is also common practice to use panels containing multiple targets adapted to specific syndromes. These panels can be restricted to a handful of viruses in the case of central nervous system (CNS) infections or can target more than 17 different agents in the case of respiratory tract infections. Despite this progress, it is still common for infectious disease specialists to be faced with cases for which a viral disease is suspected, but where all microbiological investigations remain negative or incomplete. CNS and respiratory tract infections are prototype diseases that are frequently considered of viral origin by clinicians, but cannot be proven by microbiologists. The goal of the present proposal is to take advantage of the expertise of our group, as well as the different opportunities offered by our clinical virology platform. This platform, created in part thanks to our previous SNF funding (32003B-127160), aims to link clinical investigations with more in-depth virological investigations. In the last few years, we were able to provide expertise in clinical virology for our own investigations and also for colleagues conducting investigations in the pediatric population in Europe and Africa, as well as in immunocompromised hosts. In the present proposal we aim to study CNS and respiratory tract viral diseases from different points of view: -At the level of the CNS, we will conduct two investigations. In the first one, we will address specific microbiological questions including viral pathogenesis and diagnostic issues related to enterovirus, the most frequent cause of CNS infections. In the second one, we will search for the presence of distant viral strains or new neurotropic viruses in patients with CNS encephalitis, myelitis or meningitis of unknown origin.-At the level of the respiratory tract, we will investigate lung transplant recipients and Tanzanian children with acute febrile respiratory diseases of unknown origin. These two groups of patients have been enrolled in our previous studies and selected based on their specific risk factors and their well characterized illnesses. They have been considered at high-risk of viral infections but remained negative for all known respiratory viruses. In these two groups of patients we will search for the presence of distant viral strains or new respiratory viruses.-At the microbiological level the above-mentioned investigations will use next-generation high-throughput sequencing (NGHTS) technologies as a tool for the discovery of new virus or distant variants. Beyond the technology, our aim is to link NGHTS to relevant investigations in the field of clinical virology. We consider that this technology has evolved sufficiently in 2012 to conduct these investigations. But most importantly, this can also be done due to our access to very relevant clinical specimens in highly selected cohort of patients with well-defined clinical conditions. This is an original part of our study compared to virus discovery studies performed so far.The proposal and the research plan are thus organized according not only to the clinical conditions that will be investigated, but also to the technology used. For this reason, at the technical and microbiological level the part related to enteroviral meningitis is individualized in one specific investigation and the virus discovery part in another set of investigations including both CNS and respiratory infections. At the clinical level CNS and respiratory infections concern different group of patient and are considered as distinct entities as depicted in the following figure.