HIV-1 infection-induced alteration of the cellular splicing machinery

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Whether viral spread in an HIV-1 infected cell culture is slow or fast is even nowadays still unpredictable. Among responsible host cell-specific influences processing of the viral primary transcript, i.e., alternative splicing, plays a key role. Cell type specific differences of splicing regulatory host cell proteins and differences in the phenotype of their transcripts, which in turn can be modulated as a consequence of the infection, have a substantial impact on viral replication. We propose that modulating cellular splicing through the infection represents an as-yet-undiscovered way of hostile takeover mechanism. The aim of this proposal is to identify infection-induced alternative splicing events which affect cellular transcripts whose translational products i) influence HIV-1 splicing and/or ii) viral replication by sequencing whole transcriptomes of uninfected and HIV-1-infected cells. Comparing cell-type specific transcriptomes and infection-induced alterations combined with increasing knowledge of splicing cis-regulatory elements will converge into a new fundamental understanding of HIV-1 replication.