Reannotation of the CELO genome characterizes a set of previously unassigned open reading frames and points to novel modes of host interaction in avian adenoviruses

Stefan Washietl,Frank Eisenhaber

doi:10.1186/1471-2105-4-55

Stefan Washietl, Frank Eisenhaber

Open Access

https://doi.org/10.1186/1471-2105-4-55

Copy DOI

Abstract

BackgroundThe genome of the avian adenovirus Chicken Embryo Lethal Orphan (CELO) has two terminal regions without detectable homology in mammalian adenoviruses that are left without annotation in the initial analysis. Since adenoviruses have been a rich source of new insights into molecular cell biology and practical applications of CELO as gene a delivery vector are being considered, this genome appeared worth revisiting. We conducted a systematic reannotation and in-depth sequence analysis of the CELO genome.ResultsWe describe a strongly diverged paralogous cluster including ORF-2, ORF-12, ORF-13, and ORF-14 with an ATPase/helicase domain most likely acquired from adeno-associated parvoviruses. None of these ORFs appear to have retained ATPase/helicase function and alternative functions (e.g. modulation of gene expression during the early life-cycle) must be considered in an adenoviral context. Further, we identified a cluster of three putative type-1-transmembrane glycoproteins with IG-like domains (ORF-9, ORF-10, ORF-11) which are good candidates to substitute for the missing immunomodulatory functions of mammalian adenoviruses. ORF-16 (located directly adjacent) displays distant homology to vertebrate mono-ADP-ribosyltransferases. Members of this family are known to be involved in immuno-regulation and similiar functions during CELO life cycle can be considered for this ORF. Finally, we describe a putative triglyceride lipase (merged ORF-18/19) with additional domains, which can be expected to have specific roles during the infection of birds, since they are unique to avian adenoviruses and Marek's disease-like viruses, a group of pathogenic avian herpesviruses.ConclusionsWe could characterize most of the previously unassigned ORFs pointing to functions in host-virus interaction. The results provide new directives for rationally designed experiments.

Highlights

The genome of the avian adenovirus Chicken Embryo Lethal Orphan (CELO) has two terminal regions without detectable homology in mammalian adenoviruses that are left without annotation in the initial analysis
In the central region ranging from approximately nt 6000 to 31000, most of the ORFs could be reliably assigned to proteins that have been previously described for mastadenoviruses
We propose that the originally described ORF3,4,5,6,7,15,21 do not code for proteins because (i) there are no homologs in the closely related avian adenoviruses or in other viruses/organisms, (ii) sequence analysis did not yield reasonable protein features, (iii) no corresponding transcript could be experimentally detected [13] (iv) they overlap with alternative ORFs that meet most of these criteria

Summary

Introduction

The genome of the avian adenovirus Chicken Embryo Lethal Orphan (CELO) has two terminal regions without detectable homology in mammalian adenoviruses that are left without annotation in the initial analysis. Chicken embryo lethal orphan virus (CELO) is an adenovirus infecting avian species [1,2]. Two unique terminal regions of about 6 kb and 12 kb rich in open reading frames with no homologs in mammalian adenoviruses could be found. This surprising result suggests that the basic properties of the replication cycle are similar in both groups whereas they encode a completely different set of proteins for host interaction. A few of these proteins have been functionally characterized so far

Methods

Results

Discussion

Conclusion