title: TLR-9 contributes to the antiviral innate immune sensing of rodent parvoviruses MVMp and H-1PV by normal human immune cells.
abstract: The oncotropism of Minute Virus of Mice (MVMp) is partially related to the stimulation of an antiviral response mediated by type-I interferons (IFNs) in normal but not in transformed mouse cells. The present work was undertaken to assess whether the oncotropism displayed against human cells by MVMp and its rat homolog H-1PV also depends on antiviral mechanisms and to identify the pattern recognition receptor (PRR) involved. Despite their low proliferation rate which represents a drawback for parvovirus multiplication, we used human peripheral blood mononuclear cells (hPBMCs) as normal model specifically because all known PRRs are functional in this mixed cell population and moreover because some of its subsets are among the main IFN producers upon infections in mammals. Human transformed models consisted in lines and tumor cells more or less permissive to both parvoviruses. Our results show that irrespective of their permissiveness, transformed cells do not produce IFNs nor develop an antiviral response upon parvovirus infection. However, MVMp- or H-1PV-infected hPBMCs trigger such defense mechanisms despite an absence of parvovirus replication and protein expression, pointing to the viral genome as the activating element. Substantial reduction of an inhibitory oligodeoxynucleotide (iODN) of the latter IFN production identified TLR-9 as a potential PRR for parvoviruses in hPBMCs. However, neither the iODN treatment nor an antibody-induced neutralization of the IFN-triggered effects restored parvovirus multiplication in these cells as expected by their weak proliferation in culture. Finally, given that a TLR-9 activation could also not be observed in parvovirus-infected human lines reported to be endowed with a functional TLR-9 pathway (Namalwa, Raji, and HEK293-TLR9(+/+)), our data suggest that transformed human cells do not sense MVMp or H-1PV either because of an absence of PRR expression or an intrinsic, or virus-driven defect in the endosomal sensing of the parvovirus genomes by TLR-9.
authors: Infection and Cancer Program, Division F010 and Institut National de la Santé et de la Recherche Médicale INSERM U701, German Cancer Research Center, Heidelberg, Germany.
authors: Zahari
authors: Z
authors: Raykov
authors: Svitlana P
authors: SP
authors: Grekova
authors: Rita
authors: R
authors: Hörlein
authors: Barbara
authors: B
authors: Leuchs
authors: Thomas
authors: T
authors: Giese
authors: Nathalia A
authors: NA
authors: Giese
authors: Jean
authors: J
authors: Rommelaere
authors: Rainer
authors: R
authors: Zawatzky
authors: Laurent
authors: L
authors: Daeffler
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral / Q000276:immunology; D016679:Genome, Viral / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D051379:Mice; D008915:Minute Virus of Mice / Q000235:genetics / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
chemical_list: D007370:Interferon Type I; D051217:Toll-Like Receptor 9
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