rologie i - European Congress of Virology

5 th European Congress of Virologyproteases, such as HAT, TMPRSS2, and TMPRSS4. The A/WSN/33 H1N1virus expresses a unique neuraminidase (NA) protein which is able toconvert plasminogen into plasmin and thus allows cleavage of HA in theabsence of serine proteases. Recent studies show that A/Puero Rico/8/34H1N1 virus induces the conversion of plasminogen via the annexin IIpathway, even if the NA is unable to bind with plasminogen. Therefore,processed monobasic HA can lead to infection and hyperfibrinolysis whichinitiates a strong cytokine response in mouse models. However, other hostplasminogen activators and inhibitors may also play an active role in processingHA. In this study, we investigated the possible involvement ofSerpinE1 (plasminogen activator inhibitor type 1) for the susceptibility ofthe host to IAV infections. Our results showed that SerpinE1 knock outmutants were more susceptible to H1N1 infections compared to C57BL/6Jwild type mice. The increase in susceptibility might be caused by theabsence of the inhibiting factor of fibrinolysis which may influence thepathogenesis of IAV in vivo.REF 073Search for the necrosis inducing determinants in the sequence of Peanutstunt virus strainsAleksandra OBREPALSKA STEPLOWSKA, PrzemyslawWIECZOREK, Barbara WRZESINSKA, Henryk POSPIESZNYInstitute of Plant Protection National Research Institute, Poznan,POLANDPeanut stunt virus (PSV) is a serious pathogen of legumes, belonging to theCucumovirus genus in the family Bromoviridae. PSV strains infect highrange of plant species causing different local or/and systemic symptomson them. The pathogenesis and host range depends on the strain molecularcharacteristics. Necrosis formation might constitute hypersensitiveresponse of the host aiming at isolation of the virus within adjacent cellsand its further elimination. Among PSV strains, three PSV P, Ag, andG, related to the I subgroup, are characterized on molecular level. Firsttwo are associated with subviral element satellite RNA (satRNA). Thosestrains cause in some hosts local necrotic spots, which are particularlyevident in Chenopodium quinoa. The molecular determinant(s) of necrosisformation remains still undetermined in the case of this virus. Data frompreviously characterized viruses indicate that even single point mutationwithin the whole genome, both coding and non coding can reverse theproperties of the virus in this context. In this study we prepared series ofpseudorecombinants of aforementioned strains which consist of variouscombinations of three viral genomic strands, in satRNA free and satRNAassociated versions. We tested their infectivity and virulence and hostreaction on inoculation. Our results indicate that sequence(s) responsiblefor local necrosis inductions in C. quinoa is/are located within genomicstrands and not subviral RNAs. Aknowledgement. This study was supportedby the Polish Ministry of Higher Education and Science grant NoNN310117537.REF 074Human Endogenous retrovirus Type W (HERV W) detected in immaturedendritic cells of patients with psychiatric disordersMarion SCHNEIDER 1 , Alexandra ALTMANN 1 , Karl BECHTER 2 ,Hervé PERRON 31 Experimental Anaesthesiology, University Hospital Ulm, 89081 Ulm,GERMANY; 2 Clinic for Psychiatry and Psychotherapy II, BKK Guenzburg,89312 Guenzburg, GERMANY; 3 Geneuro Innovation, 69008 Lyon,FRANCEHuman Endogenous retrovirus Type W (HERV W) has now consistentlybeen associated with Multiple Sclerosis through MSRV Env expression,but may also play a role in major psychoses and neuroinflammatory signaturesof bipolar disorders (BD) and schizophrenia (SZ). HERV W envgene encodes a protein associated with systemic inflammation and neurotoxicity,but still, neurotoxicity can be also mediated by several proinflammatory cytokines of innate immunity. As another characteristic,inflammatory diseases give rise to high amounts of circulating immaturedendritic (iDC) cells. We here asked whether these iDC also occur inpatients with major depression, BD and SZ. Primary cultures were set upfrom blood mononuclear cells (PBMC). After 3 weeks, the characteristic,highly pleomorphic and non polarized cell type occurred, and ∼1 × 105iDC were enriched per 2 × 106 PBMC originally seeded. Using flow cytometry,all cultures expressed CD11c, CD178, CD64, HLA DR and themigratory antigen CD11b, but CD14 and co stimulatory molecules CD80,CD86 were only weakly expressed. In 7 13% of these iDC, we found theHERV W Env protein by a specific monoclonal antibody. The stainingpattern of Env antigen was characteristic: asymmetric, vesicular type andmainly in the Golgi region. Env positive cytoplasmic vesicles appearedto be eventually released as microparticles or ectosomes as confirmed byflow cytometry. The current culture strategy may be relevant to isolateHERV W Env positive iDC from different patients for further studying theretroviral genome in neuroinflammation.REF 075Plasminogen Controls Inflammation and Pathogenesis of InfluenzaVirus Infections via FibrinolysisFatma BERRI 1 , Guus F. RIMMELZWAAN 2 , Michel HANSS 3 ,Emmanuel ALBINA 4 , Marie Laure FOUCAULT GRUNENWALD 1 ,Vuong B. LE 1 , Stella E. VOGELZANG VAN TRIERUM 2 , Patrica GIL 4 ,Eric CAMERER 5,6 , Dominique MARTINEZ 4 , Bruno LINA 1 , RogerLIJNEN 7 , Peter CARMELIET 8,9 , Béatrice RITEAU 1,101 VirPath, EA4610 Virologie et Pathologie Humaine, Faculté de MédecineRTH Laennec, Université Claude Bernard Lyon 1, Lyon, France;2 Department of Virology, Erasmus Medical Center, Rotterdam, NETHER-LANDS; 3 Laboratoire d’Hematologie, CBPE, Hospices Civils de Lyon,Lyon, FRANCE; 4 CIRAD, UMR CMAEE, Montpellier, France INRA,UMR1309 CMAEE, Montpellier, FRANCE; 5 INSERM U970, Paris CardiovascularCentre, Paris, FRANCE; 6 Université Paris Descartes, Paris,FRANCE; 7 Center for Molecular and Vascular Biology, KU Leuven, Leuven,BELGIUM; 8 Laboratory of Angiogenesis & Neurovascular Link,Vesalius Research Center, VIB, Leuven, BELGIUM; 9 Laboratory of Angiogenesis& Neurovascular Link, Vesalius Research Center, KU Leuven,Leuven, Belgium; 10 INRA, Nouzilly, Indre et Loire, FRANCEDetrimental inflammation of the lungs is a hallmark of severe influenzavirus infections. Endothelial cells are the source of cytokine amplification,although mechanisms underlying this process are unknown. Here, usingcombined pharmacological and gene deletion approaches, we show thatplasminogen controls lung inflammation and pathogenesis of infectionswith influenza A/PR/8/34, highly pathogenic H5N1 and 2009 pandemicH1N1 viruses. Reduction of virus replication was not responsible for theobserved effect. However, pharmacological depletion of fibrinogen, themain target of plasminogen reversed disease resistance of plasminogendeficient mice or mice treated with an inhibitor of plasminogen mediatedfibrinolysis. Therefore, plasminogen contributes to the deleterious inflammationof the lungs and local fibrin clot formation may be implicatedin host defense against influenza virus infections. Our studies suggestthat the hemostatic system might be explored for novel treatments againstinfluenza.Virologie, Vol 17, supplément 2, septembre 2013S139