rologie i - European Congress of Virology

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5 th European Congress of VirologyThursday 12 th September 2013, 8h30 – 10h30WORKSHOP 17: “VECTOR BORNE VIRAL INFECTIONS”KEYNOTES:Partnership with the FP7-EU programsEuroWN, Vectorie & WingsChairpersons: Luiza BARZON (Padova, ITALY)& Nathalie PARDIGON (Paris, FRANCE)Room Gratte Ciel 1, 2, 3Epidemiology of WN in the Mediterranean region: towards betterdiagnostics and surveillanceMiguel-Angel JIMENEZINIA, Cisa, Madrid, SPAINWest Nile virus (WNV) is one of the most relevant emerging pathogensof the World. Public health authorities worldwide have incorporated thispathogen as one of their priorities in their agendas and road maps. Thismeans surveillance, preparedness and contingency plans at National andInternational levels, to tackle with the challenge of monitoring West Nilevirus circulation in vast geographic areas, enabling capabilities to detectand diagnose efficiently every case of WNV infection.WNV cycle involves different birds as vertebrate hosts and different typesof mosquitoes as vectors. Spillover from this cycle may affect other vertebratehosts, such as horses and humans. Understanding the risk of spilloverand epidemics requires a basic knowledge on how biotic (mosquito andvertebrate species composition and diversity, phenology, diet, habitats,etc.) and abiotic (geography, climate, etc.) components affect WNV transmissiondynamics.Although having common characteristics, Europe/Mediterranean regionis not a homogeneous region in terms of eco-epidemiology for WNV, butrather exhibit a “patchy” pattern in terms of virus transmission and persistencein the field. To define these patterns precisely is the objective of theepidemiological studies carried out in each area. A good model of study isgiven by the project EuroWestNile, with teams located in different areasof WNV transmission looking at the main factors governing the epidemiologyin each location. From their comparison, it is expected to produce a listof “common” and “differential” factors governing WNV epidemiology ineach transmission setting, using parameters accurately determined locally.Epidemiological models, diagnostic tools and surveillance programs mustbe adapted to the specific situation at which they target.West Nile virus strains in Europe are as virulent as the North AmericancounterpartsByron E.E. MARTINA, Stephanie M. Lim, Penelope KORAKA, AlbertDME OSTERHAUSDepartment of Virology, Erasmus Medical Center, Rotterdam, THENETHERLANDSThe severity of West Nile virus (WNV) infection in immunocompetentanimals is highly strain dependent, ranging from avirulent to highly neuropathogenic.Reasons for susceptibility to WNV-associated neuroinvasivedisease in a minority of human cases remain unexplained. Furthermore,until recently, WNV outbreaks in Europe were limited compared to the outbreaksrecorded in the US. It is also remarkable that many of the outbreaksin humans caused by lineage 1 and 2 in Europe, were not preceded by massivebird mortality. Virulence is a multi-factorial process and many aspectsneed to be studied in order to elucidate the pathogenic force of viruses.Several parameters can be used to describe virulence such as replicationrate, immune-interfering properties, lethal dose 50, median survival time,tropism for particular cells or tissues, as well as the viral burden present ininfected tissues. In addition, virulence factors in mice differ from those thatdetermine pathogenicity in birds. It is believed that a weak immune responseallows WNV replication in the periphery and development of highviremia with an increased chance of infection of the CNS. In addition, toWNV replication in the brain, the cells involved in supporting infection inthe CNS and the resultant response to WNV may tip the balance betweenrecovery and severe neuroinvasive disease. Evidence exists that both gliaand neurons are involved in WNV pathogenesis as well as virus-relatedvirulence factors.Development of vaccines against WNVSebastian ULBERTFraunhofer Institute for Cell Therapy and Immunology, Leipzig, GER-MANYWest Nile Virus (WNV) is an emerging pathogenic and mosquito-borneflavivirus with increasing distribution worldwide. During the last coupleof years the virus became endemic in several European countries. Birdsare the natural hosts of WNV, but also mammals, including humans, can beinfected. In most cases, WNV infections remain asymptomatic or lead toflu-like symptoms. However, especially older and immunocompromisedindividuals are at risk to develop severe neurological complications such asencephalitis or meningitis, which happens in approx. 1% of the cases. Currentlyavailable WNV-vaccines include formaldehyde-inactivated virusand viral vector systems, but are only for veterinary use. Despite majorresearch efforts, there is no human vaccine on the market yet. Due tothe need to protect older people, any vaccine technology against WNVhas to especially focus on effectiveness and safety. The lecture will givean overview on WNV-vaccine development and will present EU-fundedresearch that is being carried out on this topic by the scientific consortiaVECTORIE, WINGS and EUROWESTNILE.ORAL COMMUNICATIONSREF O37Impact of vector ecology on virus amplification and spillover intohumans and livestock: the case of West Nile virus in EuropeJordi FIGUEROLA 1 , Josue MARTINEZ DE LA PUENTE 1 , AnnapaolaRIZZOLI 2 , Alexander PLATONOV 3 , Hanna BIN 4 , Joaquin MUÑOZ 1 ,Gioia CAPELLI 5 , Santiago RUIZ 6 , Roberto ROSA 2 , David ROIZ 1 , AnaVAZQUEZ 7 , Antonio TENORIO 7 , Maripaz SANCHEZ SECO 7 , RamonSORIGUER 11 EBD CSIC, Sevilla, SPAIN; 2 Fondazione Edmund March, S. Micheleall’Adige, ITALY; 3 Central Institute of Epidemiology, Moscow, RUSSIA;4 Central Virology Laboratory Ministry of Health, Ramat Gan, ISRAEL;5 Instituto Zooprofilattico Sperimentale delle Venezie, Legnaro, ITALY;6 Servicio de Control de Mosquitos, Huelva, SPAIN; 7 Instituto de SaludCarlos III, Madrid, SPAINOutbreaks of zoonotic diseases are recurrently occurring across Europe.Usually interpreted as the result of virus introductions into new areas, inmany cases outbreaks are the result of environmental conditions favouringvirus amplification or spillover into humans or livestock. Understandingthe risk of emergence of vector borne zoonotic virus implies improvingour knowledge of the interactions between vectors and vertebrates. Thisis specially relevant for West Nile virus, a flavivirus causing encephalitisamong humans that has demonstrated its capacity to overwinter in Europeand produce until recent years, reduced outbreaks in humans and horses.The virus is able to replicate in most avian species, and mosquitoes getinfected after feeding on viraemic birds. However, most mammal speciesare dead end hosts. To understand the potential of virus amplificationwe analysed the blood meal origin of mosquitoes trapped in Israel, Italy,Virologie, Vol 17, supplément 2, septembre 2013S51
5 th European Congress of VirologyRussia and Spain. Results show that some mosquito species feed mainlyon birds (with a large potential for virus amplification) while others feed onmammals only. Important differences in diet composition also occurredbetween localities, probably due to vertebrate community composition.In Spain, WNV transmission risk for birds human and horses, was estimatedbased on mosquito abundance, vectorial competence and bloodmeal origin. Estimated risk fitted reasonably well interspecific differencesin antibody prevalence and virus prevalence in mosquitoes. Vector ecologymay contribute to understand risk of zoonotic virus outbreaks acrossEurope.REF O38Characterization of Human West Nile Virus strains isolated in NorthernItalyLuisa BARZON 1,2 , Monia PACENTI 2 , Elisa FRANCHIN 1,2 , LauraSQUARZON 1 , Alessandro SINIGAGLIA 1,3 , Samuele ASNICAL 1 ,Enrico LAVEZZO 1 , Stefano TOPPO 1 , Silke CORBACH SOEHLE 4 ,Ignazio CASTAGLIUOLO 1 , Giulia MASI 1 , Sebastian ULBERT 5 ,Margherita CATTAI 2 , Riccardo CUSINATO 2 , Giorgio PALÙ 1,21 Department of Molecular Medicine, University of Padova, Padova,ITALY; 2 Clinical Microbiology and Virology, Padova University Hospital,Padova, ITALY; 3 IOV Istituto Oncologico Veneto, Padova, ITALY;4 Institut für Labortierkunde, Universität Zürich, Zurich, SWITZERLAND;5 Vaccine Technologies Unit, Fraunhofer Institute for Cell Therapy andImmunology, Leipzig, GERMANYWest Nile Virus (WNV), a flavivirus, is intrinsically maintained in anenzootic cycle between mosquitos as vectors and wild birds serving asreservoir hosts. WNV can also infect and cause disease in humans andhorses. The virus is widely distributed in Africa, Europe, the Middle East,Asia and the Americas and is able to cause neuroinvasive disease withthe potential for severe courses especially in the elderly and immunocompromisedhumans. WNV infections increasingly occur in mediterraneancountries with tendency to spread to central and northern Europe. Thus,safe and efficacious vaccines are urgently sought for WNV prophylaxis inhumans and animals. Replication deficient Modified Vaccinia virus Ankara(MVA) can be exploited as versatile viral vector in medical and veterinaryvaccine development.Here, we have generated and evaluated recombinant MVA delivering theWNV antigens E (envelope) and prM/M (precursor membrane/membrane)and fulfilling the requirements to undergo clinical testing in humans. Thestructural proteins of the WNV envelope are highly relevant vaccine antigensfor the induction of WNV specific antibody and T cell responses.Infections of human and equine cell cultures with recombinant MVAdemonstrated efficient synthesis and secretion of WNV envelope proteinsin mammalian cells non permissive for MVA replication. Primeboost immunizations in BALB/c mice induced high levels of WNV specificantibodies. Moreover, vaccinations with recombinant MVA in HLAA2.1/HLA DR1 transgenic H 2 class I/class II knockout mice resulted inthe induction and efficient expansion of WNV specific CD8+ T cells. Thus,results from vaccinations in two different mouse models demonstratedsolid immunogenicity of MVA WNV vector vaccines. Further evaluationin different animal models is warranted to evaluate protective efficacyagainst WNV and to demonstrate the potential of the recombinant MVAas candidate vaccines in humans.West Nile virus (WNV) is an emerging pathogen that is circulating in Northeastern Italy and causing disease in humans since 2008. Aim of this studywas the investigation of the spread of WNV strains in north eastern Italytaking advantage of the special surveillance programme for WNV infectionthat was activated in Veneto Region in 2008 and enhanced in 2010.The pathogenic potential of isolated WNV strains was also investigated.During 2008 2009, several human cases of WNV disease caused by anendemic lineage 1a strain, named Ita09, were identified in areas surroundingthe Po river. Since 2010, cases have been recorded in nearby northernareas, where, in 2011, both lineage 1a and 2 were detected. Two novelhuman lineage 1a strains were identified in 2011 by full genome sequencingand phylogenetic analysis. One of these strains, called Livenza, wasresponsible of a relatively large outbreak with over 50 human infections in2012. Both the Ita09 and Livenza strains had a prolin at codon 249 of theNS3 protease/helicase, which has been associated with increased WNVtransmissibility and virulence. In vitro experiments demonstrated higherstability and activity of the NS3 protease/helicase with prolin at codon 249than other NS3 mutants. Pathogenicity studies on the WNV Ita09 straindemonstrated high neuroivasive potential and lethality in mouse models.In the mouse model, different organs were involved by WNV infectionwith the highest viral load detected in brain, stomach, and gut. Activationof markers of innate immune response was demonstrated in infectedorgans.REF O39Recombinant vaccinia MVA expressing E and prM/M proteins of WestNile Virus for vaccine generationGerd SUTTER 1 , Martina KASERER 1 , Asisa VOLZ 1 , Sylvia JANY 1 ,Stephanie LIM 2 , Byron MARTINA 21 Institute for Infectious Diseases and Zoonoses,Chair for Virology, LMU,Munich, GERMANY; 2 Virosience Lab, Erasmus Medical Center, Rotterdam,THE NETHERLANDSREF O40Sylvatic origin and geographic spread of St. Louis encephalitis virusSandra JUNGLEN 1 , Anne KOPP 1 , Thomas GILLESPIE 2 , DanielHOBELSBERGER 3 , Alejandro ESTRADA 4 , James HARPER 5 ,Richard MILLER 5 , Isabella ECKERLE 1 , Marcel MÜLLER 1 , LarsPODSIADLOWSKI 6 , Fabian LEENDERTZ 3 , Christian DROSTEN 11 Institute of Virology, Bonn, GERMANY; 2 Emory University, Atlanta,USA; 3 Robert Koch Institute, Berlin, GERMANY; 4 University of Mexico,Mexico City, MEXICO; 5 University of Michigan, Ann Arbour, USA;6 Institute of Evolutionary Biology and Ecology, Bonn, GERMANYSt. Louis encephalitis virus (SLEV) is the prototypic mosquito borne flavivirusin the Americas. The virus is transmitted between Culex mosquitoesand birds in North and South America. The geographic and ecologicalorigins of SLEV remain obscure.In an ecological investigation in a tropical rainforest in Palenque NationalPark, Mexico, we discovered an ancestral variant of SLEV in Culexnigripalpus mosquitoes.The tentatively named SLEV Palenque strains were distinct from all presentlyknown SLEV strains showing only 94.2 – 95.7% amino acid identityto epidemic SLEV strains and forming a highly distinct phylogenetic cladewithin the SLEV species. Cell culture studies of SLEV Palenque versusepidemic SLEV (MSI 7) revealed no growth differences in insect cells, buta clear inability of SLEV Palenque to replicate in cells from several SLEVhost species permissive for MSI 7 replication (birds, cotton rats, free tailedbats). Only cells from nonhuman primates and neotropical fruit batswere moderately permissive. Phylogeographic reconstruction suggestedthat the common ancestor of all epidemic SLEV strains has existed in anarea between southern Mexico and Panama circa 330 years before present.Expansion of the epidemic lineage occurred in two waves, the first representingemergence near the area of origin and the second involving almostparallel appearances of virus in the lower Mississippi and Amazonas deltaregions. We were able to link the emergence of a major epidemic arboviruswith anthropogenic ecosystem invasion during colonial times.S52 Virologie, Vol 17, supplément 2, septembre 2013
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