rologie i - European Congress of Virology

5 th European Congress of Virologyvascular leakage may be a direct result of virus infection or an immuneresponse mediated indirect effect. The main target cells are mononuclearphagocytes, endothelial cells and hepatocytes; the liver being a key targetfor the virus which was described as susceptible to IFN host response andto induce apoptosis. However, to better understand the first liver cell alterationsafter virus infection, the protein profile of in vitro CCHFV infectedHepG2 cells was analysed using two complementary quantitative proteomicapproaches, 2D DIGE and iTRAQ. A set of 243 differentially expressedproteins was identified. Bioinformatics analysis (Ingenuity PathwaysAnalysis) revealed multiple host cell pathways and functions altered afterCCHFV infection, with notably 106 proteins related to cell death, including79 associated with apoptosis. Four protein networks emerged withassociated pathways involved in virus entry and exit, protein synthesis,acute phase response, oxidative stress, ubiquitination, or lipid metabolism.These data suggest that CCHFV seems to hijack host proteins topromote its replication and spread. This work gives informations on virushost interactions leading to CCHV pathogenesis, and offers an unparalleledopportunity of the description of possible targets for antiviral research.REF 238Dating the origin of variola virus and other orthopoxvirusesIrina BABKINA, Igor BABKINInstitute of Chemical Biology and Fundamental Medicine, Novosibirsk,RUSSIAThe data on the structure of conserved genes of the New World orthopoxvirusesand unclassified Yoka poxvirus were used for a Bayesian dating oftheir independent evolution. This reconstruction estimates the time whenan orthopoxvirus ancestor was transferred to the North American continentas approximately 50 thousand years ago (TYA) and allows for relation ofthis time interval with the global climate changes (with one of the shorttern warmings during the Last Ice Age). The onset of the Yoka poxvirusevolution was assessed as approximately 90 TYA. Availability of a largenumber of genome sequences of various cowpox virus strains provided fora comprehensive analysis of the orthopoxvirus evolutionary history. Sucha study is especially topical in view of the postulated role of this virusin the evolution of various orthopoxviruses, namely, as an ancestor virus.The computations have demonstrated that the orthopoxviruses divergedfrom the ancestor virus to form the current species about 10 TYA, whilethe ancestor of horsepox virus separated about 3 TYA. An independentevolution of taterapox, camelpox, and variola viruses commenced approximately3.5 TYA. Study of the geographic distribution areas of the hosts ofthese three orthopoxviruses suggests the hypothesis on the region of theirorigin. It is likely that these viruses first emerged in Africa, in the regionof the Horn of Africa, and that the introduction of camels to East Africainduced their divergent evolution.REF 239New transgenic mouse model revealed crucial role of type I interferonsignaling during early stages of Henipavirus infectionKévin P. DHONDT, Cyrille MATTHIEU, Marie CHALONS, JoséphineM. REYNAUD, Branka HORVATCIRI INSERM U1111, CNRS UMR5308, UCBL1, ENS Lyon, Lyon,FRANCEThe Nipah virus (NiV) is highly lethal zoonotic paramyxovirus that emergedin Malaysia in 1998 from a wild reservoir of Pteropus fruit bats. NiV reemerged in Bangladesh few years later causing human outbreaks annually.The study of NiV immunopathogenesis required the development of anadequate small animal model. Therefore, we recently characterized a newanimal model of NiV infection based on mice which have a deletion inInterferon Type I Receptor (IFNAR KO). We showed that in contrast towild type (wt) mice, these mice are highly susceptible to NiV infection bydifferent routes of infection and develop fatal encephalitis with pathologyand immunohistochemical features similar to what was found in humans.We further analyzed cellular and molecular mechanism of resistance of wtmice to lethal NiV infection. Surprisingly, the resistance to NiV was completelypreserved in mice deleted for sensors of the innate immune systemsuggesting the importance of constitutive, rather than virus induced IFNI signaling in the control of NiV infection. Furthermore, while infectionseems to be stopped at very early stages in intraperitoneally injected wtmice, the intracranial NiV infection leads in these mice to systemic spreadof the virus with lethal outcome. These data suggested that some interferontype I (IFN I) producing cells may play the important role in the earlycontrol of NiV infection. On going experiments should elucidate unknownaspects of Nipah virus immunopathogenesis and help us to develop newstrategies to control this highly lethal infection.REF 240Surface proteins of the recently identified African Henipavirus areable to promote viral entry, cell fusion and cytopathic effects in arange of cell lines from Human, Simian and Bat hostsPhilip LAWRENCE 1 , Jan Felix DREXLER 2 , Victor Max CORMAN 2 ,Beatriz ESCUDERO PEREZ 1 , Valentina VOLCHKOVA 1 , MarcelMÜLLER 2 , Christian DROSTEN 2 , Viktor VOLCHKOV 11 CIRI, INSERM U1111, Lyon, FRANCE; 2 Institute of Virology, Universityof Bonn Medical Centre, Bonn, GERMANYThroughout history the emergence of new infectious diseases of animalorigin has caused significant problems for human health. Bats have beenshown to serve as reservoirs for a multitude of infectious agents, includingHenipa, Filo, Corona and Lyssaviruses. Although Henipaviruses aretraditionally restricted to Pteropus bats of South Asia, the recent identificationof distinct viral clades in phylogenetic relation to Henipavirusesin different bat species in five African countries raises the possibility thatthese highly pathogenic viruses may not be as geographically restricted aspreviously imagined. In the absence of isolated infectious African Henipavirus,we have performed experiments with the viral entry proteins Fand G from a representative African strain (M74a) aimed at understandingif this virus presents the same broad cross species tropism as its Henipacounterparts. When the M74a surface proteins are cross expressed withthose of Nipah virus, the M74a G protein is able to replace the NiV Gprotein but with delayed fusion kinetics for a range of cell lines from differentspecies. Co expression of M74a G and F proteins in simian andhost bat cell lines results in rapid cytopathic effects. Pseudotyped MLVreporter infection assays were used to measure the ability of these viralsurface proteins to mediate entry into target cells. Entry mechanisms ofthe African Henipavirus will be discussed further. Results suggest that thisvirus could be expected to display a similar cell tropism to that of the otherHenipa viruses and therefore present a risk for zoonosis.REF 241Crimean Congo hemorrhagic fever virus regulate apoptotic pathwaysin situAli MIRAZIMI 1,2,3 , Yee Joo TAN 4 , Helen KARLBERG 1,51 Swedish Institute for communicable Disease Control, Stockholm,SWEDEN; 2 University of Linköping, Linköping, SWEDEN; 3 NationalVeterinary Institute, Uppsala, SWEDEN; 4 National University of Singapore,Singapore, SINGAPORE; 5 Karolinska Institute, Stockholm,SWEDENCrimean Congo hemorrhagic fever virus (CCHFV) is a member of the Nairovirusgenus of the family Bunyaviridae and it causes a severe disease withhigh mortality rates (∼30%) in human. We have previously demonstratethat CCHFV NP has a conserved cleavage site for caspase 3. Furthermore,we found that this motif, DEVD, is subjected to caspase cleavage duringS186 Virologie, Vol 17, supplément 2, septembre 2013