Project description:We describe the transcriptional response to infection of human umbilical vein endothelial cells (Huvec) with different rubella virus strains
Project description:Rubella virus infection during pregnancy can result in abortion, stillbirth and severe defects in embryogenesis resulting in congenital rubella syndrome (CRS). Low vaccination coverage in developing regions results in estimated 100,000 CRS cases in infants per year with a mortality rate over 30%. The molecular pathomechanisms and potential treatments remain largely unexplored. Endothelial cells (EC) of the placenta are infected by rubella virus (RuV). RuV reduced angiogenic and migratory capacity of primary human EC whereas cell cycle and apoptosis rate were not affected. Next generation sequencing analysis revealed an induction of antiviral type I and III interferons (IFN) that induced angiogenesis-inhibiting cytokines such as CXCL10. The transcriptional profile induced by RuV resembled the effects of IFN-β treatment. The cell culture data were confirmed using human serum from RuV IgM-positive patients that showed similar increase in CXCL10 and inhibited angiogenesis. RuV-mediated inhibition of angiogenesis was reversed by treatment with blocking and neutralizing antibodies targeting CXCL10 and IFN-β receptor. The data identify an important role for anti-viral IFN-mediated induction of CXCL10 in controlling EC function during RuV infection
Project description:This study uses proteome microarray technology/data to identify predictive biomarkers of neutralizing antibody response and potential new correlates of protective immunity in rubella virus serology.
Project description:The propensity of viruses to acquire genetic material from relatives and possibly from infected hosts makes them excellent candidates as vectors for horizontal gene transfer. However, virus-mediated acquisition of host genetic material, as deduced from historical events, appears to be rare. Here, we report spontaneous and surprisingly efficient generation of hybrid virus/host DNA molecules in the form of minicircles during infection of Beta vulgaris by Beet curly top Iran virus (BCTIV), a single-stranded DNA virus. The hybrid minicircles replicate, become encapsidated into viral particles, and spread systemically throughout infected plants in parallel with the viral infection. Importantly, when co-infected with BCTIV, B. vulgaris DNA captured in minicircles replicate and is transcribed in other plant species that are sensitive to BCTIV infection. Thus, we have likely documented in real time the initial steps of a possible path of virus-mediated horizontal transfer of chromosomal DNA between plant species.
Project description:Ebola virus can cause a severe and often fatal hemorrhagic fever in humans and other mammals, known as Ebola virus disease (EVD),the mechanism of how this pathogenesis comes about is not well understood, It is assumed that miRNA may have important roles in virus infection response. To better understand the function of miRNA in EBOV infection disease, we undertook a miRNA profiling analysis using the whole blood of EBOV infection patients.
Project description:RNA interference (RNAi) functions as a potent antiviral immunity in plants and invertebrates, however whether RNAi plays antiviral roles in mammals remains unclear. Here, using human enterovirus 71 (HEV71) as a model, we showed HEV71 3A protein as an authentic viral suppressor of RNAi during viral infection. When the 3A-mediated RNAi suppression was impaired, the mutant HEV71 readily triggered the production of abundant HEV71-derived small RNAs with canonical siRNA properties in cells and mice. These virus-derived siRNAs were produced from viral dsRNA replicative intermediates in a Dicer-dependent manner, loaded into AGO, and were fully active in degrading cognate viral RNAs. Recombinant HEV71 deficient in 3A-mediated RNAi suppression was significantly restricted in human somatic cells and mice, whereas Dicer-deficiency rescued HEV71 infection independently of type I interferon response. Thus, RNAi can function as an antiviral immunity, which is induced and suppressed by a human virus, in mammals.
