Characterising the role of the Cajal Body during a productive adenovirus infection

作者: Laura White

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摘要: Human adenoviruses (Ads) are DNA viruses believed to hold potential as gene therapy vectors. However, Ad vectors often express residual late structural proteins, which stimulate immune responses resulting in rapid clearance of the vector. Therefore a greater understanding mechanisms controlling expression is required. During phase adenovirus 5 (Ad5) infection it was previously shown that nuclear compartment involved RNA metabolism known Cajal body (CB) disassembled from 1-6 punctate domains per cell into numerous microfoci. Furthermore, marker protein CBs, p80 coilin, suggested play role proteins. exact function coilin unknown. The aim this investigation determine roles and additional CB proteins during infection. Immunofluorescence microscopy utilised investigate redistribution key following Ad5 A549 cells. Whilst redistributed CBs microfoci, another protein, termed survival motor neuron (SMN), nucleoplasm. To assess SMN infection, depleted cells by interference (RNAi). Cells were infected with virus yield, levels mRNA assessed. Depletion reduced yield decreased synthesis early, intermediate Although mostly unaffected, export mRNAs abrogated coilin-depleted This indicated plays transport. Similar depletion significantly yield. contrast resulted significant decreases capsid whilst non-structural either increased or unaffected. found reduce early transcription altered alternative splicing patterns mRNAs. splicing. This uncovered involvement two very distinct infection. first report suggesting for export. Further study now required identify cellular other also warranted. splicing, indicating may be Additional work define precise species.

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