rologie i - European Congress of Virology

5 th European Congress of VirologyREF 574Possible Involvement of Beta herpesviruses HHV 6 and HHV 7 andparvovirus B19 Infection in the Development of EncephalopathyModra MUROVSKA 1 , Svetlana CHAPENKO 1 , Santa RASA 1 , SilvijaROGA 2,3 , Zaiga NORA KRUKLE 11 A.Kirchenstein Institute of Microbiology and Virology, Riga Stradins University,Riga, LATVIA; 2 Chair of Pathology, Riga Stradins University,Riga, LATVIA; 3 Riga 1st Hospital, Riga, LATVIAEncephalopathy is a syndrome of global brain dysfunction with unclearaetiology. HHV 6 and HHV 7 are neurotropic viruses associated with awide variety of neurologic disorders. Involvement of B19 in neurologicpathologies is rarely reported.Our study aims to investigate the frequency of B19 and HHV 6, HHV7 infection markers in meningeal and brain tissues of individuals withunspecified encephalopathy. 34 individuals with and 34 without signs ofencephalopathy were enrolled in the study. nPCR was used to detect B19,HHV 6 and HHV 7 DNA in autopsy specimens (dura and pia mater, braintissue) and to define HHV 6 variant. Significantly higher frequency of viralDNAs detection was found in specimens from individuals with encephalopathycomparing to the control group (32/34 vs. 25/34, p=0.044). Nodifference was detected regarding the presence of B19 (17/34 vs. 9/34,p=0.079) and HHV 7 DNA (21/34 vs. 21/34). Frequency of single HHV6 infection (8/34 vs. 1/34, p=0.027) and co infections (29/34 vs. 14/34,p=0.0003) was higher in encephalopathy specimens, single HHV 7 infectionin control group’s samples (2/34 vs. 9/34, p=0.044). Frequency of B19infection/co infection was higher in pia mater, HHV 6 in brain tissue andpia mater, HHV 7 in brain tissue specimens of individuals with encephalopathy.In all HHV 6 positive samples HHV 6B variant was recognized.Meningeal and brain tissues are sites of B19, HHV 6, HHV 7 persistency.Simultaneous study of these viral infections and their activity stages arerequired to identify the relation with the development of encephalopathy.REF 575Identification of viral determinants involved in Borna Disease Virusinterference with human neurogenesisChloé SCORDEL 1 , Marielle COCHET 1 , Marion SZELECHOWSKI 2 ,Daniel GONZALEZ DUNIA 2 , Marc ELOIT 1 , Muriel COULPIER 11 UMR1161 de virologie, ENVA INRA ANSES, Maisons Alfort, FRANCE;2 INSERM, U1043, Toulouse, FRANCEBorna disease virus (BDV) is a neurotropic virus causing neurologicaldisorders and encephalitis in horse and sheep. BDV antigens can be foundin human and the infection could be associated with the development ofpsychiatric disorders. By using human Neural Progenitor Cells (hNPCs)in culture, we previously demonstrated that BDV interferes with humanneurogenesis by inducing the death of newly formed neurons. Our researchnow focuses on the identification of viral determinants responsible for thisinterference. We used lentiviral vectors containing genes encoding 3 viralproteins, the X protein, the nucleoprotein (N), and the phosphoprotein (P)and demonstrated that these 3 proteins neither interfere with hNPCs proliferationnor with atroglial differentiation. Likewise, the X protein does notimpair neuronal differentiation. On the contrary, N and P strongly impairneuronal differentiation, resulting in a 25 and 50% decrease in the numberof neurons, respectively. No death was observed in differentiated cellsexpressing N and P, indicating that the two proteins inhibit neuronal differentiationrather than trigger neuronal apoptosis. We next focused on thecharacterization of the molecular pathways impaired by P. We found analteration of two proteins known to be involved in neurogenesis: the transcriptionalrepressor REST was up regulated and one of its targets, SCG10,was down regulated. Our results demonstrate that the phosphoprotein ofBDV specifically impairs neurogenesis. We are currently pursuing thecharacterization of the cellular and molecular mechanisms altered.REF 576Human endogenous retroviruses of the HERV W family are upregulatedby the JC polyomavirus in human astrocytesElena ULERI 1 , Elena ULERI 1 , Serra CATERINA 1 , GiuseppeMAMELI 1 , Ilker K SARIYER 2 , Kamel KHALILI 2 , Antonina DOLEI 11 Department of Biomedical Sciences, University of Sassari, Sassari,ITALY; 2 Department of Neuroscience, Center for Neurovirology, TempleUniversity School of Medicine, Philadelphia, USAThe ubiquitous JCV polyomavirus causes progressive multifocal leukoencephalopathyin patients severely immunosuppressed or with autoimmunediseases treated with immunosuppressive antibodies. In most of thesediseases, upregulation of HERV W/MSRV/syncytin 1 endogenous retroviruseswas reported. Since the HERV W/MSRV/syncytin 1 are potentiallyneuropathogenic, we wondered about their interactions with JCV, thatcould contribute to neurodegeneration. Thus, human primary fetal astrocytesand the U87MG cell line were infected by JCV or transfected withexpression plasmids carrying early or late JCV genes, to monitor HERVW/MSRV/syncytin 1 expression, or that of constructs carrying the syncytin1 promoter. Infection by JCV upregulated both MSRV like and syncytinenv transcripts. Transient transfection showed that both JCV early and lateproteins stimulate the transcription of HERV W/MSRV/syncytin 1 envgenes. As for the HERV W promoter activity in presence of JCV proteins,gene reporter experiments with constructs carrying the full length syncytin1 promoter, or promoter deletion mutants, co transfected with JCVearly or late plasmids were carried out. Data indicate that the full lengthpromoter is upregulated by both JCV proteins. Deletion of the upstream(cellular) regulatory region indicate that the stimulatory effect lies on the5 ′ LTR (viral) moiety. Due to the identities between the 5 ′ LTR of MSRVand syncytin 1, it is likely that up regulation by JCV antigens of bothMSRV and syncytin 1 requires mainly the viral moiety of their promoters.S280 Virologie, Vol 17, supplément 2, septembre 2013