Naslov
Analiza transkriptoma mišjeg citomegalovirusa
(Analysis of murine cytomegalovirus transcriptome)

Autori
Vanda Juranić Lisnić

Vrsta, podvrsta i kategorija rada
Ocjenski radovi, doktorska disertacija

Fakultet
Medicinski fakultet

Mjesto
Rijeka

Datum
08.11

Godina
2013

Stranica
154

Mentor
Astrid Krmpotić

Neposredni voditelj
Joanne Trgovcich

Ključne riječi
mišji citomegalovirus; MCMV; transkriptom; ekspresija gena; izbjegavanje imunološkog odgovora; aktivacijski receptori Ly49
(murine cytomegalovirus; MCMV; transcriptome; gene expression; NK cell evasion; activating Ly49 receptors)

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA