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Analysis of murine cytomegalovirus transcriptome (CROSBI ID 381527)

Ocjenski rad | doktorska disertacija

Vanda Juranić Lisnić Analysis of murine cytomegalovirus transcriptome / Astrid Krmpotić (mentor); Joanne Trgovcich (neposredni voditelj). Rijeka, Medicinski fakultet u Rijeci, . 2013

Podaci o odgovornosti

Vanda Juranić Lisnić

Astrid Krmpotić

Joanne Trgovcich

engleski

Analysis of murine cytomegalovirus transcriptome

Human cytomegalovirus (HCMV) is a ubiquitous human pathogen responsible for devastating congenital disease and life-threatening complications in immune-suppressed patients. Available treatments have many shortcomings and effective vaccine is still lacking. Major obstacles to progress in vaccine and antiviral drug development are (1) species specificity of HCMV, and (2) gaps in our understanding of viral genes and their interaction with host genes. First limitation is circumvented by the use of model animal viruses, especially murine cytomegalovirus (MCMV). We sought to alleviate the second problem by studying MCMV transcriptome using two approaches: classical cDNA library analysis and next generation sequencing (RNASeq). This dual analysis revealed incredible complexity of MCMV transcriptome, detected numerous novel viral spliced and unspliced transcripts as well as transcription from intergenic regions, and showed that expression levels of viral transcripts vary by several orders of magnitude. Unexpectedly, most top expressed genes were of unknown functions and were improperly annotated. Therefore, this analysis provides the first comprehensive overview of MCMV transcriptome, underscores the necessity of transcriptomic analyses in providing evidence-based genome annotation and could serve as the first step towards re-annotation of MCMV genome. The most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs [18, 84], was shown to also code for a novel protein(s). This is the first viral transcript that functions both as a noncoding RNA and an mRNA. In this work it is also shown that this transcript’s 5’ UTR plays a role in NK cell recognition of infected cells via activating Ly49 receptors. Analysis of host transcriptome showed that lytic infection revealed that many unexpected gene groups are disregulated in response to the infection. Such systematic analysis may shed new light on cytomegalovirus pathogenesis and suggests new areas of research.

murine cytomegalovirus; MCMV; transcriptome; gene expression; NK cell evasion; activating Ly49 receptors

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Podaci o izdanju

154

08.11.2013.

obranjeno

Podaci o ustanovi koja je dodijelila akademski stupanj

Medicinski fakultet u Rijeci

Rijeka

Povezanost rada

Temeljne medicinske znanosti