rologie i - European Congress of Virology

5 th European Congress of Virologyimportant interaction sites between the stem and the trimer core thatare involved in stabilizing the post fusion trimer. In addition, we showthat both transmembrane domains of E are not only essential for virusassembly, but also for efficient fusion, most likely contributing to thelate stages of membrane merger. Our data provide evidence for bothintra and inter trimeric E protein interactions mediated by the stemanchor region and thus extend the existing models of flavivirus membranefusion.REF 166Early mechanisms in the life cycle of ocular adenovirusesRickard STORM, Niklas ARNBERGUmeå University, Department of Clinical Microbiology, Division of Virology,Umeå, SWEDENEpidemic keratoconjunctivitis (EKC) is an ocular infection that is mainlycaused by adenovirus type 8 (Ad8), Ad19 and Ad37 and affects roughly20 30 million individuals every year, worldwide. EKC is a severe andcontagious disease, and is characterized by conjunctivitis, keratitis, pain,edema, lacrimation, hemorrhages and decreased vision that may last formonths or years and in rare cases can lead to blindness. EKC causing Adshave been shown to bind to the two terminal sialic acids of a branchedhexasaccharide that corresponds to the glycan in the GD1a ganglioside1.Viral attachment to ocular cells is mediated by the knob domain of thefiber protein, which is anchored to the viral capsid by the penton baseprotein. The penton bases are located in each of the twelve corners of theicosahedral capsid and contains integrin interacting motifs such as RGD(Arginine Glycine Aspartic acid), which are known to be used by multipleAds, including Ad37, for interaction with aV integrins. This interactionhas been shown to be important for efficient cellular entry and endosomalescape by multiple Ad types. Via homology modulation and bioinformaticanalysis we identified other potentially exposed integrin interacting motifs.We have also seen that specific integrin blocking antibodies as well assoluble peptides that mimick the integrin interacting motifs inhibited Ad37infection of corneal cells. In summary, our preliminary data suggest thatEKC causing Ads interact with additional integrins besides the previouslyidentified alphaV integrins.REF 168TIM and TAM receptors mediate dengue virus infectionLaurent MEERTENS 1,2,3 , Xavier CARNEC 1,2,3 , Manuel PERERALECOIN 1,2,3 , Rasika RAMDASI 1,2,3 , FlorenceGUIVEL-BENHASSINE 4 , Erin LEW 5 , Greg LEMKE 5 , OlivierSCHWARTZ 4 , Ali AMARA 1,2,31 INSERM U944, Laboratoire de Pathologie et Virologie Moléculaire,Hôpital Saint-Louis, Paris, FRANCE; 2 Institut Universitaired’Hématologie, Hôpital Saint-Louis, Paris, FRANCE; 3 University ParisDiderot, Sorbonne Paris Cité, Hôpital St., Paris, FRANCE; 4 Unité Viruset Immunité, Institut Pasteur, Paris, FRANCE; 5 Molecular NeurobiologyLaboratory, Immunobiology and Microbial Pathogenesis Laboratory, TheSalk Institute, La Jola, USADengue viruses (DV) are responsible for the most medically relevantarboviral diseases. Molecular interactions that occur between DV and thehost cell during virus entry are poorly understood, hampering the developmentof novel antiviral strategies. Here, we identify TIM and TAMproteins, which are receptors that mediate the phosphatidylserine (PtdSer)– dependent phagocytic engulfment and removal of apoptotic cells, as DVentry factors. Cells poorly susceptible to DV become strongly infectedwhen expressing either TIM-1 or TIM-4, from the TIM family, or AXL orTYRO3, from the TAM receptor tyrosine kinase family. Conversely, additionof anti-TIM or anti-TAM antibodies, or silencing the molecules insusceptible cells, inhibits DV infection. TIM receptors mediate DV entryby directly interacting with virion-associated PtdSer. TAM-mediated DVinfection relies on the indirect recognition of PtdSer by the TAM ligandGas6, which bridges virus to the target cell. This dual mode of virus recognitionby TIM and TAM receptors reveals how DV usurp the apoptotic cellclearance pathway for infectious entry.Virologie, Vol 17, supplément 2, septembre 2013S165