rologie i - European Congress of Virology

5 th European Congress of Virology15. HIGHLY PATHOGENIC VIRUSESPosters: REF 230 to REF 251REF 230The V Protein of Tioman Virus Is Incapable of Blocking Type I InterferonSignaling in Human CellsPierre Olivier VIDALAIN 1,2 , Grégory CAIGNARD 1,2 , MarianneLUCAS HOURANI 1,2 , Kevin P. DHONDT 3,4 , Jean LouisLABERNARDIÈRE 1,2 , Thierry PETIT 5 ,YvesJACOB 6 , BrankaHORVAT 3,4 , Frédéric TANGY 1,21 Unité de Génomique Virale et Vaccination, Institut Pasteur, Paris,FRANCE; 2 CNRS UMR 3569, Paris, FRANCE; 3 INSERM U758, EcoleNormale Supérieure de Lyon, Lyon, FRANCE; 4 University of Lyon 1, Lyon,FRANCE; 5 Zoo de La Palmyre, Les Mathes, FRANCE; 6 Unité de Génétique,Papillomavirus et Cancer Humain, Institut Pasteur, Paris, FRANCEThe capacity of a virus to cross species barriers is determined by thedevelopment of bona fide interactions with cellular components of newhosts, and in particular its ability to block IFN alpha/beta antiviral signaling.Tioman virus (TioV), a close relative of mumps virus (MuV), hasbeen isolated in giant fruit bats in Southeast Asia. Nipah and Hendraviruses, which are present in the same bat colonies, are highly pathogenicin human. Despite serological evidences of close contacts between TioVand human populations, whether TioV is associated to some human pathologyremains undetermined. Here we show that in contrast to the V proteinof MuV, the V protein of TioV (TioV V) hardly interacts with humanSTAT2, does not degrade STAT1, and cannot block IFN alpha/beta signalingin human cells. In contrast, TioV V properly binds to human STAT3and MDA5, and thus interferes with IL 6 signaling and IFN beta promoterinduction in human cells. Because STAT2 binding was previously identifiedas a host restriction factor for some Paramyxoviridae, we establishedSTAT2 sequence from giant fruit bats, and binding to TioV V was tested.Surprisingly, TioV V interaction with STAT2 from giant fruit bats isalso extremely weak and barely detectable. Altogether, our observationsquestion the capacity of TioV to appropriately control IFN alpha/betasignaling in both human and giant fruit bats that are considered as itsnatural host.REF 231Arenaviruses differentially subvert type I IFN induction and activationof mitochondrial apoptotic pathway via RIG I/MAVSChristelle PYTHOUD, Stefan KUNZUniversity of Lausanne, Institute of Microbiology, Lausanne,SWITZERLANDA hallmark of arenavirus infection is the virus ability to subvert host cellinnate immunity and to suppress the induction of type I interferons (IFNs)via the RIG I/MAVS pathway. The major IFN antagonist of arenavirusesis the viral nucleoprotein (NP), which blocks activation and nuclear translocationof IRF3 in response to virus infection. The RIG I/MAVS pathwayhas recently been linked to virus induced mitochondrial apoptosis via IRF3and Bax in addition to its prominent role in activation of the cellular typeI IFN response. In the present study we sought to investigate the role ofthis novel virus induced apoptotic pathway in the context of arenavirusinfection using the prototypic arenavirus lymphocytic choriomeningitisvirus (LCMV) as a model. Using functional assays and imaging studies,we found that LCMV infection neither results in cytochrome C release,nor in activation of caspases 9, 3 and 7. Interestingly, we found that LCMVwas unable to prevent activation of RIG I/MAVS mediated mitochondrialapoptosis induced by superinfection with sendai virus (SeV) or vesicularstomatitis virus (VSV). The data suggest that LCMV evades activationof mitochondrial apoptosis via RIG I/MAVS, but is unable to block thepathway. Considering the efficient suppression of type I IFN induction byLCMV, our results indicate that arenaviruses evolved to selectively blockIRF3 mediated induction of type I IFN, but not IRF3 mediated regulationof mitochondrial apoptosis.REF 232Inhibition of Crimean Congo hemorrhagic fever virus replication byantiviral compoundsOlivier FERRARIS 1 , Marie MOROSO 2 , Olivier PERNET 3 , MichèleBOULOY 4 , Glaucia PARANHOS BACCALÀ 2 , ChristophePEYREFITTE 11 IRBA, Lyon, FRANCE; 2 Fondation Mérieux, Lyon, FRANCE; 3 UCLA,Los Angeles, USA; 4 Institut Pasteur, Paris, FRANCECrimean Congo hemorrhagic virus (CCHFV) causes viral hemorrhagicfever with high case fatality rates and is endemic in Europe, Africa, andAsia. The causative CCHF virus is an enveloped, segmented negativestranded RNA virus of the family Bunyaviridae, genus nairovirus. Thediscorvery of novel CCHFV inhibitors remains an imortant priority inlight of the lack of currently specific treatment. To enter cells, viruses bindto a variety of host cell receptors, which determine the entry mechanism,host range and pathogenesis of each virus. Following binding, viruses gainaccess to intracellular compartment by fusing with plasma membrane orby internalization in endosomes. Considering this possibility, compoundswere tested for antiviral activity. In this in vitro study, we have evaluatedthe potential antiviral activity of two compounds against Crimean Congohemorrhagic virus. Plaque formation inhibition and virus yield reductionassays of strains of CCHFV in Vero E6 and HuH7 cells were evaluated. The50% inhibitory concentration values for the first tested compound rangedfrom 28 to 43 M, and ranged from 10.8 to 15.7 M for the second. Timeof addition studies demonstrated that compounds might have a direct effecton viral particle infectivity and spread. Our study highlights the interest ofusing compound that target entry pathway to treat CCHF virus infection.This approach has to be considered for the development of future antiviralcompounds targeting CCHF virus.REF 233Development of a cell based assay to image SKI 1/S1P activity for highthoughput screensEmanuela Maria PASI 1 , Joel Ramos DA PALMA 1 , Clara GALAN 1 ,Prudence DONOVAN 2 , Daniel CONSTAM 2 , Antonella PASQUATO 1 ,Stefan KUNZ 11 Institute of Microbiology,University Hospital Center and University ofLausanne, Lausanne, SWITZERLAND; 2 Swiss Federal Institute of TechnologyLausanne, School of Life Sciences, Swiss Institute for ExperimentalCancer Research, Lausanne, SWITZERLANDArenaviruses are lethal human pathogens with no FDA approved vaccinesand drugs. Envelope glycoprotein precursors (GPCs) of arenaviruses arecleaved by the cellular protease Subtilisin Kexin isozyme (SKI 1)/Site 1Protease (S1P), a key regulator of lipid homeostasis, ER stress response,and lysosomal biogenesis. Since this step is fundamental for the formationof infectious virions, SKI 1/S1P is a promising antiviral target. We showedthat SKI 1/S1P inhibitors block arenavirus spread and clear persistentlyinfected cells. However, systemic inhibition of SKI 1/S1P will affect its cellularfunctions with unwanted side effects. Notably, while cellular proteinprocessing takes place in the mid Golgi, the GPCs of Lassa virus (LASV)and lymphocytic choriomeningitis virus (LCMV) undergo maturation inS184 Virologie, Vol 17, supplément 2, septembre 2013