rologie i - European Congress of Virology

5 th European Congress of Virologythe whole human exome sequence of patients who were severely infectedwith influenza during the pandemic that did not have severe comorbidities.Through this approach we have identified potential SNP variantsthat may affect susceptibility to influenza infection. We have used RNAiscreening in A549 cells to knockdown genes where SNP variants havebeen identified, followed by infection with influenza to validate this datain vitro. To gain more insight into the effect of these variants we have alsocompared influenza infection of human lymphoblastoid cell lines, whichhave either the ‘reference/wild type’ genotype or the SNP variant identifiedin our exome analysis associated with severe influenza. The results ofthis powerful strategy to identify host factors that affect the outcome ofinfluenza infections will be discussed.REF O107Characterization of one novel interferon stimulated gene participatingin the type I interferon block to HIV 1 infectionCaroline GOUJON 1 , Olivier MONCORGÉ 2 , Christopher WARD 1 ,Tomas DOYLE 1 , Hélène BAUBY 1 , Stéphane HUÉ 3 , WendyS. BARCLAY 2 , Reiner SCHULTZ 4 , Michael H. MALIM 11 Department of Infectious Diseases, King’s College London, London,UNITED KINGDOM; 2 Division of Infectious Diseases, Imperial CollegeLondon, London, UNITED KINGDOM; 3 Department of Infection, UniversityCollege London, London, UNITED KINGDOM; 4 Department ofMedical & Molecular Genetics, King’s College London, London, UNITEDKINGDOMType I interferon (IFN) induces a potent block to the early steps of HIV1 infection in some cell types, including primary CD4+ T cells, macrophages,THP 1 and U87 MG cells. We have previously shown that othercell types, such as T cell lines, were unable to block HIV 1 infection followingIFN stimulation despite normal IFN responsiveness. Consequently,we used a comparative transcriptomic analysis in permissive versus restrictivecells following IFN treatment to generate a list of interferon stimulatedgenes (ISGs) with potential anti HIV 1 activity. We screened a series of candidateISGs using a lenviral vector containing an antisense and inducibleexpression cassette.The overexpression in U87 MG cells of one of these ISGs, previously notknown to be anti viral, conferred a potent block to HIV 1 infection (up to10 50 fold decrease in infection efficiency). The block was observed withseveral strains of HIV 1, and both with wild type and VSV G pseudotypedviruses. This gene was highly induced by type 1 IFN in primary cells as wellas U87 MG and THP 1 cells, but its expression was almost undetectablein T cell lines. Importantly, the silencing of this gene partially rescuedthe IFN induced block to HIV 1 infection, both in U87 MG and THP 1cells (7 10 fold rescue out of 35 50 fold decrease in infection with IFN).Ongoing efforts include determining the range of anti viral specificityof this ISG and identifying the specific step at which it blocks HIV 1infection.Taken together, we have identified one new and potent effector of the typeI IFN response against HIV 1.Virologie, Vol 17, supplément 2, septembre 2013S85