Abstract
Human cytomegalovirus is an opportunistic double-stranded DNA virus with one of the largest viral genomes known. The 235 kB genome is divided in a unique long (UL) and a unique short (US) region which are flanked by terminal and internal repeats. The expression of HCMV genes is highly complex and involves the production of protein coding transcripts, polyadenylated long non-coding RNAs, polyadenylated anti-sense transcripts and a variety of non-polyadenylated RNAs such as microRNAs. Although the function of many of these transcripts is unknown, they are suggested to play a direct or regulatory role in the delicately orchestrated processes that ensure HCMV replication and life-long persistence. This review focuses on annotating the complete viral genome based on three sources of information. First, previous reviews were used as a template for the functional keywords to ensure continuity; second, the Uniprot database was used to further enrich the functional database; and finally, the literature was manually curated for novel functions of HCMV gene products. Novel discoveries were discussed in light of the viral life cycle. This functional annotation highlights still poorly understood regions of the genome but more importantly it can give insight in functional clusters and/or may be helpful in the analysis of future transcriptomics and proteomics studies.
Highlights
Human cytomegalovirus (HCMV) is a common opportunistic pathogen with a worldwide prevalence of 45–100% depending on age, location, gender and socio-economic status (Cannon et al, 2010)
We provide an updated, non-exhaustive functional annotation of the HCMV genome based on curation of the literature, previous reviews and the Uniprot database (Supplementary Table 1)
We focussed on updating the functional annotation of the complete HCMV genome
Summary
Human cytomegalovirus (HCMV) is a common opportunistic pathogen with a worldwide prevalence of 45–100% depending on age, location, gender and socio-economic status (Cannon et al, 2010). Initial infection is followed by life-long persistence characterized by periodical reactivation episodes. Initial infection and reactivation of the virus usually does not result in morbidity (Boeckh and Geballe, 2011); the virus can cause devastating complications in neonates and immunecompromised patients such as birth defects, systemic failure and rejection of the transplanted organ (Griffiths, 2006; Pass et al, 2006; Kenneson and Cannon, 2007; Crough and Khanna, 2009). A later study identified an additional four new protein coding transcripts, i.e., RL8A, RL9A, UL150A, and US33A. A recent study confirmed this hypothesis and revealed a previously unprecedented complexity of HCMV gene expression when they identified an additional 604 protein coding ORFs, most of which were very short and located upstream of longer ORFs (Stern-Ginossar et al, 2012).
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