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The novel human astroviruses: an emerging human infection that needs to be characterized at the epidemiological, clinical and virological levels

English title The novel human astroviruses : an emerging human infection that needs to be characterized at the epidemiological, clinical and virological levels
Applicant Kaiser Laurent
Number 165873
Funding scheme Project funding (Div. I-III)
Research institution Laboratoire de Virologie Service des Maladies Infectieuses Hôpitaux Universitaires de Genève
Institution of higher education University of Geneva - GE
Main discipline Internal Medicine
Start/End 01.04.2016 - 31.12.2019
Approved amount 600'000.00
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All Disciplines (2)

Discipline
Internal Medicine
Medical Microbiology

Keywords (7)

Astrovirus; Clinical microbiology; Virology; Clincial virology; Virus discovery; Diagnostic; Emerging virus

Lay Summary (French)

Lead
Notre précédent financement par le FNS nous avons a permis d’identifier de nouveaux astrovirus humains comme étant une cause d’infections disséminées (cas de méningites) et possiblement d’infections respiratoires. N’existant à ce jour pas de test moléculaire commercial permettant leur détection par des laboratoires d’analyses de routine, ces nouveaux astrovirus restent méconnus par les cliniciens. Contrairement aux astrovirus humains classiques, il n’existe pas à ce jour de système de culture cellulaire. Notre but est de mettre à profit notre expertise en virologie fondamentale et en diagnostique ainsi que notre position au sein du laboratoire de routine en virologie pour effectuer des investigations microbiologiques et cliniques centrées sur ces nouveaux astrovirus.
Lay summary

Notre précédent financement par le FNS nous avons a permis d’identifier de nouveaux astrovirus humains comme étant une cause d’infections disséminées (cas de méningites) et possiblement d’infections respiratoires. N’existant à ce jour pas de test moléculaire commercial permettant leur détection par des laboratoires d’analyses de routine, ces nouveaux astrovirus restent méconnus par les cliniciens. Contrairement aux astrovirus humains classiques, il n’existe pas à ce jour de système de culture cellulaire. Notre but est de mettre à profit notre expertise en virologie fondamentale et en diagnostique ainsi que notre position au sein du laboratoire de routine en virologie pour effectuer des investigations microbiologiques et cliniques centrées sur ces nouveaux astrovirus.

 

Au niveau microbiologiques, des qRT-PCR spécifiques pour les différents astrovirus humains émergents (MLB et VA) seront développées afin de permettre leur détection dans des échantillons cliniques. Nous nous centrerons également sur la  mise au point d’un système de culture cellulaire en ne nous limitant pas à l’utilisation de lignées cellulaires « classiques » mais également en testant des lignées primaires intestinales ou des systèmes de culture 3D. Le développement d’un système de culture cellulaire permettra d’obtenir des stocks viraux quantifiés et d’envisager le design d’immunoassay.

 

Au niveau cliniques, nous investiguerons par qRT-PCR la prévalence de ces nouveaux astrovirus humains au sein de différentes cohortes (cohorte #1: screening des selles reçus au laboratoire de routine durant deux années successives; cohorte #2: LCR de meningo-encéphalites virales; cohorte #3: selles, plasma ou LCR de patients adultes greffés de moelle ; cohorte #4: selles ou plasma de patients pédiatriques greffés (organes solides)). Leur diversité génétique sera également étudiée par analyse du génome viral complet (HTS, prélèvements avec fortes charges virales) ou de la région ORF2 par séquençage classique.

Direct link to Lay Summary Last update: 25.04.2016

Responsible applicant and co-applicants

Employees

Publications

Publication
Fecal Components Modulate Human Astrovirus Infectivity in Cells and Reconstituted Intestinal Tissues
Pérez-Rodriguez Francisco J., Vieille Gael, Turin Lara, Yildiz Soner, Tapparel Caroline, Kaiser Laurent (2019), Fecal Components Modulate Human Astrovirus Infectivity in Cells and Reconstituted Intestinal Tissues, in mSphere, 4(6), 1-13.
Investigation of the Plasma Virome from Cases of Unexplained Febrile Illness in Tanzania from 2013 to 2014: a Comparative Analysis between Unbiased and VirCapSeq-VERT High-Throughput Sequencing Approaches
Williams Simon H., Cordey Samuel, Bhuva Nishit, Laubscher Florian, Hartley Mary-Anne, Boillat-Blanco Noémie, Mbarack Zainab, Samaka Josephine, Mlaganile Tarsis, Jain Komal, d’Acremont Valerie, Kaiser Laurent, Lipkin W. Ian (2018), Investigation of the Plasma Virome from Cases of Unexplained Febrile Illness in Tanzania from 2013 to 2014: a Comparative Analysis between Unbiased and VirCapSeq-VERT High-Throughput Sequencing Approaches, in mSphere, 3(4), 1-6.
Novel human astroviruses in pediatric respiratory samples: A one-year survey in a Swiss tertiary-care hospital.
Cordey S, Zanella M C, Wagner N, Turin L, Kaiser L (2018), Novel human astroviruses in pediatric respiratory samples: A one-year survey in a Swiss tertiary-care hospital., in Journal of medical virology, 1-4.
Detection of novel astroviruses MLB1 and MLB2 in the sera of febrile Tanzanian children
Cordey Samuel, Hartley Mary-Anne, Keitel Kristina, Laubscher Florian, Brito Francisco, Junier Thomas, Kagoro Frank, Samaka Josephine, Masimba John, Said Zamzam, Temba Hosiana, Mlaganile Tarsis, Docquier Mylène, Fellay Jacques, Kaiser Laurent, D’Acremont Valérie (2018), Detection of novel astroviruses MLB1 and MLB2 in the sera of febrile Tanzanian children, in Emerging Microbes & Infections, (1), 27-27.
Usutu virus in cerebrospinal fluid: A two-year survey in a tertiary care hospital, Geneva, Switzerland.
Cordey Samuel, Vieille Gael, Turin Lara, Kaiser Laurent (2017), Usutu virus in cerebrospinal fluid: A two-year survey in a tertiary care hospital, Geneva, Switzerland., in Journal of medical virology, 609-611.
Novel and classical human astroviruses in stool and cerebrospinal fluid: comprehensive screening in a tertiary care hospital, Switzerland.
Cordey Samuel, Vu Diem-Lan, Zanella Marie-Celine, Turin Lara, Mamin Aline, Kaiser Laurent (2017), Novel and classical human astroviruses in stool and cerebrospinal fluid: comprehensive screening in a tertiary care hospital, Switzerland., in Emerging microbes & infections, (9), 84-84.

Associated projects

Number Title Start Funding scheme
148512 Swiss Transplant Cohort Study 01.02.2014 Cohort Studies Large
146993 Investigations of enterovirus meningitis and central nervous system/respiratory diseases of unrecognized viral etiology. 01.04.2013 Project funding (Div. I-III)

Abstract

Thanks to our ongoing SNF-funded virus discovery project, we have recently identified an astrovirus MLB2 as a cause of meningitis and disseminated infection. Up to now, this virus and the other non-classical astroviruses were not recognized as a distinct cause of human diseases. Our main general objective is therefore to expand our findings and establish the relationship between the novel human astroviruses and specific diseases like meningitis. To reach our objective, we will address thoughtfully several questions at the clinical and the microbiological level as follows:Part A. Microbiological investigations1. To establish a panel of validated and quantitative real-time RT-PCR assays covering all human astroviruses.2. To establish in vitro models for isolation of non-classical human astroviruses and establish a viral stock that will be used for further virological investigations.3. To use NGS analysis for predefined cases (positive and negative) to complete the viral phylogeny and and analyze their full-length genome sequence diversity.Part B. Clinical investigations1. To assess the prevalence and epidemiology of human astrovirus infection in a hospital-based setting by a systematic screening of all of these viruses in unselected stools sent to our laboratory. 2. To establish the incidence of human astrovirus infection in case of acute meningo-encephalitis over a 2-years time period; this will be done thanks to a prospective cohort enrolling all adults and children hospitalized with an acute meningo-encephalitis in our hospital.3. To establish whether astroviruses are a frequent cause of disseminated diseases and their potential clinical impact in highly immuncompromised patients. This will be done thanks to the two specific following cohorts:oAdult allogeneic hematopoietic stem cell transplant recipientsoPediatric solid organ (mainly liver) transplant recipients
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