Survey of Chimeric mRNAs in HIV Infected Patient RNA-SEQ Data

Abstract

It has been demonstrated that the HIV virus is integrated into the host DNA. The integrated provirus may be transcriptionally silent or active, and its regulation depends on viral or host factors [1]. Due to viral sequence integration into host genome, there are fusion gene cases at DNA level. However, there are other ways of producing fusion sequences at RNA level and trans-splicing is most typical example of RNA fusion. Trans-splicing is a special form of alternative splicing, like alternative cis-splicing, which can facilitate diversification of genotypes and phenotypes. This phenomenon is not only observed in host cells where trans-splicing takes places between genes of same species, but also observed between viral mRNA and host mRNA [2]. Earlier studies showed that HIV Nef mRNA is able to trans-splice to both non-HIV viral (SV40) and host mRNAs [3]. Revealing all possible trans-splicing events by traditional methods is merely impossible but with advent of next generation sequencing technology and vast databases of raw sequencing data, rare events of trans-splicing cases can be unveiled. We are interested in viral RNA and host RNA trans-splicing cases and beyond. Next generation sequencing allows detection of all types of fusion events, not only generated by trans-splicing but also generated by previously unreported mechanism. We used RNA-Seq data from HIV infected patient T-cells or cell culture which were downloaded from NCBI SRA database. Nearly 1 billion short reads were aligned to to reference sequence composed of human genome and viral genome sequences. We utilized split alignments of short reads to both human genome and viral genome found in infected patients in order to survey chimeric mRNAs. In addition to trans-spliced transcripts, we also identified non splice junction transcripts. The results of this study has potential to contribute to understanding of viral mechanisms yet to be discovered.

Publication
In 10th The International Symposium on Health Informatics and Bioinformatics

Related