Enterotropic viruses and antiviral strategies


  HEADDr COLBÈRE-GARAPIN Florence / fcolbere@pasteur.fr
  MEMBERSAUTRET Arnaud / BALANANT Jean / Dr BLONDEL Bruno / Dr DELPEYROUX Francis
Jegouic Sophie / Dr Joffret Marie-Line / Dr MARTIN-LATIL Sandra / Dr PELLETIER Isabelle


  Annual Report

Human enteroviruses (HEVs) belong to the Picornaviridae family that is one of the most important groups of human and animal pathogens. Virus multiplication in the intestine is generally asymptomatic, and the most serious acute pathologies caused by HEVs are diseases of the central nervous system. They include paralytic poliomyelitis, most cases of which are caused by poliovirus (PV). Massive anti-polio immunization programs have greatly reduced the prevalence of poliomyelitis worldwide. However, the disease has not been eradicated and low vaccine coverage in some developing countries allows the emergence of pathogenic, vaccine-derived PV (VDPVs). We are studying the evolution and biology of enteric viruses, in particular circulating VDPVs.

Genetic exchange between PV and coxsackie A viruses (FD and the WHO Collaborative Center for research on enteroviruses). Pathogenic VDPV strains implicated in poliomyelitis epidemics in Madagascar in 2002 and 2005 have been investigated. The studies have been performed in collaboration with the Pasteur Institute of Antananarivo, and show that the emergence of these VDPVs is associated with complex genetic recombination between PV and local coxsakie A virus strains that belong to the same phylogenetic group of HEVs. The genetic exchanges between PV and coxsackie A viruses contribute to the phenotypic diversity and possibly to the pathogenicity of VDPVs (Romanenkova and coll. J Clin. Microbiol. 2006; Rakoto-Andrianarivelo and coll. J. Clin. Microbiol., 2005).

The evolution of VDPVs in sewage from a highly immunized population has been studied in collaboration with L.M. Shulman’s laboratory (Shulman and coll. PLoS ONE, 2006).

Complete cure of persistent PV infections by antiviral siRNAs. Cultures persistently infected by PV for several months have been cured by specific siRNA treatment. This is, to our knowledge, the first demonstration of the complete cure by chemical antiviral siRNAs of entire cultures of cells productively infected by a human virus for several months (Saulnier* and coll, Mol. Ther., 2006).

Human intestinal cells spontaneously cured of persistent PV infection have an increased resistance to apoptosis. Our analyses strongly suggest that persistent virus infection selects cells partially resistant to apoptosis (Labadie* and coll, J. Virol, in press).

Relationships between promyelocytic leukemia protein, p53 and apoptosis during PV infection have been studied in collaboration with M.K. Chelbi-Alix’s laboratory (Pampin and coll., J. Virol., 2006).

Signaling pathways involved in PV-induced apoptosis in human neuronal cells. We have investigated the role of stress-activated protein kinases in cellular pathways involved in neuronal cell death caused by PV (Autret and coll.).

Signaling pathways involved in rotavirus-induced apoptosis in human epithelial cells. The role of Bcl-2 family members in rotavirus-induced apoptosis has been investigated to elucidate the mechanism of rotavirus-induced gastroenteritis (Martin-Latil and coll.).

Keywords: poliovirus, rotavirus, persistent infection, apoptosis, signaling pathways

colbere-garapin.jpg

PV receptor (green) and F-actin (red) on the basolateral (left panel) and apical face (right panel) of enterocytes.



  Publications

Publications 2006 of the unit on Pasteur's references database




Activity Reports 2007 - Institut Pasteur
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