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Rhinoviruses associated with lower respiratory diseases: genetic variability and replications site

English title Rhinoviruses associated with lower respiratory diseases: genetic variability and replications site
Applicant Kaiser Laurent
Number 113426
Funding scheme Project funding
Research institution Laboratoire de Virologie Service des Maladies Infectieuses Hôpitaux Universitaires de Genève
Institution of higher education University of Geneva - GE
Main discipline Infectious Diseases
Start/End 01.01.2007 - 31.12.2009
Approved amount 361'718.00
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All Disciplines (2)

Discipline
Infectious Diseases
Respiratory Diseases

Keywords (4)

Rhinovirus; molecular epidemiology; respiratory viruses; picornavirus

Lay Summary (English)

Lead
Lay summary
Human rhinovirus (HRV) is the most frequent cause of infections. As immunity is strain-specific and more than 100 serotypes are described, HRVs will continue to circulate in humans the only reservoir identified yet. In healthy individuals this “common cold” virus causes most often self-limited respiratory diseases but in immunocompromised patients and subjects with chronic respiratory diseases HRV is a frequent cause of complications. Despite this significant impact, the molecular characterization of both clinical isolates and reference strains(serotypes) is poor and this classification does not take in account strains identified by molecular methods only. This later point is of importance since HRVs have a high propensity to evolve by accumulation of mutations or by recombination. The goal of the present project is to provide genotypic information by sequencing relevant genes like VP1 (the target of most immune pressure), the 3C protease and part of the 3D polymerase.
In a second part we propose to analyze the in-host viral evolution (including full-length genome analysis) both in immunocompromised and immunocompetent hosts. This will be done thanks to the previous observation that rhinoviruses can cause chronic infections in lung transplant recipients. In few cases of prolonged rhinoviral infection we have further observed that some clinical strains switch in vivo from a temperature sensitive to a temperature tolerant virus (more likely to be adapted to the lower respiratory tract). We expect through full-length sequence of these strains to identify cis-acting sequences involved in the regulation of virus replication and temperature adaptation.
In a third part we will analyze lung biopsies of lung transplant recipients in order to determine the presence of rhinoviral replication within the lower respiratory epithelium.
This transitional project aims to better understand the genotypic variability of HRV causing lower respiratory diseases and to characterize the molecular determinants of adaptation to the lower respiratory tract.The investigation of lung transplant recipients will be critical to assess in host evolution (chronic infection), to determine whether HRV infects the lower respiratory tract, and to assess the real clinical impact of this virus.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

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Associated projects

Number Title Start Funding scheme
146151 Rhinovirus et entérovirus: déterminants génomiques et phénotypes associés 01.04.2013 Project funding
127160 Respiratory viruses: improving molecular diagnostic tools and assessment of clinical impact in lung transplant recipients 01.01.2010 Project funding
101670 A prospective assessment of the role of respiratory viruses and atypical bacteria in patients hospitalized with severe lower respiratory tract infections 01.01.2004 Project funding
127159 Picornavirus respiratoires: variabilité génomique et adaptation 01.01.2010 Project funding

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