rologie i - European Congress of Virology

5 th European Congress of Virologyfluorescent proteins allow specific labeling of cells and cellular compartments.Furthermore, functional proteins as calcium indicators, channelrhodopsinsor e.g. ferritin are expressed from novel vectors. Here we areproviding an update on the rabies virus vector toolbox, allowing bothretrograde and anterograde labeling of neurons, mono synaptic tracing ofneuronal connections, and studying the function and activity of individualneurons.REF 570CMV encephalitis in AIDS patientsSven GRÜTZMEIER 1 , Johan BERGSTRÖM 1 , Eric SANDSTRÖM 1 ,Inger NENNESMO 21 South hospital, Stockholm, SWEDEN; 2 Department of Pathology, KarolinskaUniversity Hospital, huddinge, Stockholm, SWEDENA cohort of 243 patients with HIV infection was followed 1989 1996 atVenhälsan from diagnosis of the infection to death. All were investigatedfor reactivation of CMV infection by measuring CMV antigen and/orCMV PCR in the blood and signs of CMV encephalitis and CMV retinitis,as well as other opportunistic infections. 221 patients died with CD4count 100 × 106/L. Postmortem brain examinations were performed on 78/221 and 6/22 respectively.Of the 78 patients 70 (90%) had signs of reactivated CMV infectionmeasured by blood tests and on morphological examination 43 (55%) hadCMV encephalitis, 16 (21%) toxoplasmosis, 15 (19%) CNS lymphoma,6 (8%) progressive multifocal leukoencephalopathy (PML), 3 (4%) HIVencephalitis and 3 (4%) fungal infection. CMV lesions in the brain wereprimarily found along the walls of the ventricles. 15 patients (19%) hadmore than one opportunistic infection. Of the patients with CMV encephalitis90% also had CMV retinitis. Of the six autopsied patients with CD4counts >100 × 106/L the brain was normal in 2 patients, 2 had infarction,1 HIV encephalitis and 1 glioblastoma. CMV encephalitis is the predominantCNS opportunistic infection in this material and also appears to bethe cause of death either alone or together with other opportunistic infections.Opportunistic CNS infections are not common if the patients diewith a CD4 count >100 × 106/L. HIV encephalitis is not common in anypatient group, one reason could be that all patients had been treated withzidovudin for their HIV infection.REF 571From rabies virus to new drugs candidatesMonique LAFON, Mireille LAFAGE, Christophe PREHAUDInsitut Pasteur NeuroImmunologie Virale, Paris, FRANCERabies virus is a strictly neurotropic virus which multiplies in the centralnervous system of mammals. During the propagation of the virus into thenervous system from one neuron to the next order neuron, the infectedneurons rarely encounter apoptosis. Avoiding premature apoptosis can beseen as an adaptive mechanism to facilitate rabies virus propagation fromthe site of inoculation by bite, up to the salivary glands where it is excreted.We showed that virulent strains of rabies virus, not only avoid prematureapoptosis but also enhance the survival of neurons in culture by activatingsurvival and neurogenesis signaling pathways. Rabies virus infectionenhances the regrowth of axons of adult mouse dorsal root sensory neuronsand promotes neurite outgrowth of human neuroblastoma cells (SH SY5Ycells lines). Among the five proteins of the virus, we determined that theenvelope glycoprotein, the G protein, drives the neuro survival phenotype.We identified the active polypeptide part of the protein and the major roleplayed by its cellular partner, the microtubule associated serine threoninekinase 2, MAST 2. When delivered in cells by a lentivector, the activepolypeptide was observed to favour the healing of axons of human postmitotic dopaminergic neurons (NT2 N cells) which have been woundedby needle scratches. This new neuro protective compound might foundpromising application in neuro degenerative medicine, demonstrating thatviruses can be a source of new drug candidates.REF 572Characterization of the Mouse Neuroinvasiveness of Selected EuropeanStrains of West Nile VirusStephanie LIM, Penelope KORAKA, Sander VAN BOHEEMEN, JoukeROOSE, Dick JAARSMA, David VAN DE VIJVER, AlbertOSTERHAUS, Byron MARTINAErasmus Medical Centre, Rotterdam, THE NETHERLANDSWest Nile virus (WNV) has caused outbreaks and sporadic infections inCentral, Eastern and Mediterranean Europe for over 45 years. Most strainsresponsible for the European and Mediterranean basin outbreaks are classifiedas lineage 1. In recent years, WNV strains belonging to lineage 1and 2 have been causing outbreaks of neuroinvasive disease in humans incountries such as Italy, Hungary and Greece, while mass mortality amongbirds was not reported. This study characterizes three European strainsof WNV isolated in Italy (FIN and Ita09) and Hungary (578/10) in termsof in vitro replication kinetics on neuroblastoma cells, LD50 values inC57BL/6 mice, median day mortality, cumulative mortality, concentrationof virus in the brain and spinal cord, and the response to infectionin the brain. Overall, the results indicate that strains circulating in Europebelonging to both lineage 1 and 2 are highly virulent and that Ita09 and578/10 are more neurovirulent compared to the FIN strain.REF 573Association between grey matter volumes and Herpes Simplex VirusType 1 specific humoral immunity in Alzheimer’s diseaseRoberta MANCUSO 1 , Francesca BAGLIO 2 , Monia CABINIO 2,4 , ElenaCALABRESE 3 , Ambra HERNIS 1 , Milena ZANZOTTERA 1 , FrancaGUERINI 1 , Raffaello NEMNI 3,4 , Mario CLERICI 1,41 Laboratory of Molecular Medicine and Biotechnology, Don GnocchiFoundation IRCCS, Milan, ITALY; 2 Magnetic Resonance Laboratory, DonC. Gnocchi Foundation IRCCS, Milan, ITALY; 3 Dept. Neurorehabilitation,Don C. Gnocchi Foundation IRCCS, Milan, ITALY; 4 Department ofPhysiopathology and Transplantation, University of Milan, Milan, ITALYBackground and aims: HSV1 is suspected to be a risk factor for Alzheimerdisease (AD): it can infect the regions of the central nervous systemwhich are affected by AD associated pathological changes (hippocampal,temporal region). Therefore we evaluated the possible correlations betweenHSV1 humoral immunity and cortical grey matter (GM) volumein AD patients. Materials and methods: 134 subjects were enrolled inthe study: 83 AD (mean age 77+7 yrs; 50 M) (NINCDSADRDA criteria/DSMIV R) and 51 healthy controls (HC) age and sex matched. Patientsunderwent a Mini Mental State Evaluation (MMSE) and HSV1 IgG antibodies(Ab index) were tested in serum by ELISA test. 44 AD HSV1seropositive patients underwent a Magnetic Resonance Imaging (MRI)examination to investigate cortical gray matter (GM) volume (Voxel BasedMorphometry study). ApoE genotyping was also obtained. To highlightthe correlation between GM and HSV1 values, a regression analysis wasperformed on MRI data including for each subject GM maps and HSVantibody values. Statistical analyses were performed on SPM8 software.Results: Seroprevalence and Ab titers were comparable in two groups.High HSV1 titers (Ab index >75 ◦ percentile) were present in 35.8% of ADvs. 16% of HC (p=0.024). Notably, HSV1 Ab titers were positively correlatedwith cortical volume bilaterally in temporal and orbitofrontal cortex(clusters corrected FWE