A new mouse model reveals a critical role for host innate immunity in resistance to Rift Valley fever.

2.50
Hdl Handle:
http://hdl.handle.net/10033/132986
Title:
A new mouse model reveals a critical role for host innate immunity in resistance to Rift Valley fever.
Authors:
do Valle, Tânia Zaverucha; Billecocq, Agnès; Guillemot, Laurent; Alberts, Rudi; Gommet, Céline; Geffers, Robert; Calabrese, Kátia; Schughart, Klaus ( 0000-0002-6824-7523 ) ; Bouloy, Michèle; Montagutelli, Xavier; Panthier, Jean-Jacques
Abstract:
Rift Valley fever (RVF) is an arthropod-borne viral disease repeatedly reported in many African countries and, more recently, in Saudi Arabia and Yemen. RVF virus (RVFV) primarily infects domesticated ruminants, resulting in miscarriage in pregnant females and death for newborns and young animals. It also has the ability to infect humans, causing a feverish syndrome, meningoencephalitis, or hemorrhagic fever. The various outcomes of RVFV infection in animals and humans argue for the existence of host genetic determinants controlling the disease. We investigated the susceptibility of inbred mouse strains to infection with the virulent RVFV ZH548 strain. Compared with classical BALB/cByJ mice, wild-derived Mus m. musculus MBT/Pas mice exhibited earlier and greater viremia and died sooner, a result in sharp contrast with their resistance to infection with West Nile virus and influenza A. Infection of mouse embryonic fibroblasts (MEFs) from MBT/Pas mice with RVFV also resulted in higher viral production. Microarray and quantitative RT-PCR experiments showed that BALB/cByJ MEFs displayed a significant activation of the type I IFN pathway. In contrast, MBT/Pas MEFs elicited a delayed and partial type I IFN response to RVFV infection. RNA interference-mediated inhibition of genes that were not induced by RVFV in MBT/Pas MEFs increased viral production in BALB/cByJ MEFs, thus demonstrating their functional importance in limiting viral replication. We conclude that the failure of MBT/Pas murine strain to induce, in due course, a complete innate immune response is instrumental in the selective susceptibility to RVF.
Affiliation:
Unité Génétique Fonctionnelle de la Souris, Institut Pasteur, Paris, France.
Citation:
A new mouse model reveals a critical role for host innate immunity in resistance to Rift Valley fever. 2010, 185 (10):6146-56 J. Immunol.
Journal:
Journal of immunology (Baltimore, Md. : 1950)
Issue Date:
15-Nov-2010
URI:
http://hdl.handle.net/10033/132986
DOI:
10.4049/jimmunol.1000949
PubMed ID:
20937849
Type:
Article
Language:
en
ISSN:
1550-6606
Appears in Collections:
publications of the department infection genetics (INFG)

Full metadata record

DC FieldValue Language
dc.contributor.authordo Valle, Tânia Zaveruchaen
dc.contributor.authorBillecocq, Agnèsen
dc.contributor.authorGuillemot, Laurenten
dc.contributor.authorAlberts, Rudien
dc.contributor.authorGommet, Célineen
dc.contributor.authorGeffers, Roberten
dc.contributor.authorCalabrese, Kátiaen
dc.contributor.authorSchughart, Klausen
dc.contributor.authorBouloy, Michèleen
dc.contributor.authorMontagutelli, Xavieren
dc.contributor.authorPanthier, Jean-Jacquesen
dc.date.accessioned2011-06-10T14:15:40Zen
dc.date.available2011-06-10T14:15:40Zen
dc.date.issued2010-11-15en
dc.identifier.citationA new mouse model reveals a critical role for host innate immunity in resistance to Rift Valley fever. 2010, 185 (10):6146-56 J. Immunol.en
dc.identifier.issn1550-6606en
dc.identifier.pmid20937849en
dc.identifier.doi10.4049/jimmunol.1000949en
dc.identifier.urihttp://hdl.handle.net/10033/132986en
dc.description.abstractRift Valley fever (RVF) is an arthropod-borne viral disease repeatedly reported in many African countries and, more recently, in Saudi Arabia and Yemen. RVF virus (RVFV) primarily infects domesticated ruminants, resulting in miscarriage in pregnant females and death for newborns and young animals. It also has the ability to infect humans, causing a feverish syndrome, meningoencephalitis, or hemorrhagic fever. The various outcomes of RVFV infection in animals and humans argue for the existence of host genetic determinants controlling the disease. We investigated the susceptibility of inbred mouse strains to infection with the virulent RVFV ZH548 strain. Compared with classical BALB/cByJ mice, wild-derived Mus m. musculus MBT/Pas mice exhibited earlier and greater viremia and died sooner, a result in sharp contrast with their resistance to infection with West Nile virus and influenza A. Infection of mouse embryonic fibroblasts (MEFs) from MBT/Pas mice with RVFV also resulted in higher viral production. Microarray and quantitative RT-PCR experiments showed that BALB/cByJ MEFs displayed a significant activation of the type I IFN pathway. In contrast, MBT/Pas MEFs elicited a delayed and partial type I IFN response to RVFV infection. RNA interference-mediated inhibition of genes that were not induced by RVFV in MBT/Pas MEFs increased viral production in BALB/cByJ MEFs, thus demonstrating their functional importance in limiting viral replication. We conclude that the failure of MBT/Pas murine strain to induce, in due course, a complete innate immune response is instrumental in the selective susceptibility to RVF.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshDisease Models, Animalen
dc.subject.meshFibroblastsen
dc.subject.meshGene Expression Profilingen
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshImmunity, Innateen
dc.subject.meshImmunohistochemistryen
dc.subject.meshMaleen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshOligonucleotide Array Sequence Analysisen
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen
dc.subject.meshRift Valley Feveren
dc.titleA new mouse model reveals a critical role for host innate immunity in resistance to Rift Valley fever.en
dc.typeArticleen
dc.contributor.departmentUnité Génétique Fonctionnelle de la Souris, Institut Pasteur, Paris, France.en
dc.identifier.journalJournal of immunology (Baltimore, Md. : 1950)en

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