Unique sequence features of the Human Adenovirus 31 complete genomic sequence are conserved in clinical isolates

Abstract

BackgroundHuman adenoviruses (HAdV) are causing a broad spectrum of diseases. One of the most severe forms of adenovirus infection is a disseminated disease resulting in significant morbidity and mortality. Several reports in recent years have identified HAdV-31 from species A (HAdV-A31) as a cause of disseminated disease in children following haematopoetic stem cell transplantation (hSCT) and liver transplantation. We sequenced and analyzed the complete genome of the HAdV-A31 prototype strain to uncover unique sequence motifs associated with its high virulence. Moreover, we sequenced coding regions known to be essential for tropism and virulence (early transcription units E1A, E3, E4, the fiber knob and the penton base) of HAdV-A31 clinical isolates from patients with disseminated disease.ResultsThe genome size of HAdV-A31 is 33763 base pairs (bp) in length with a GC content of 46.36%. Nucleotide alignment to the closely related HAdV-A12 revealed an overall homology of 84.2%. The genome organization into early, intermediate and late regions is similar to HAdV-A12. Sequence analysis of the prototype strain showed unique sequence features such as an immunoglobulin-like domain in the species A specific gene product E3 CR1 beta and a potentially integrin binding RGD motif in the C-terminal region of the protein IX. These features were conserved in all analyzed clinical isolates. Overall, amino acid sequences of clinical isolates were highly conserved compared to the prototype (99.2 to 100%), but a synonymous/non synonymous ratio (S/N) of 2.36 in E3 CR1 beta suggested positive selection.ConclusionUnique sequence features of HAdV-A31 may enhance its ability to escape the host's immune surveillance and may facilitate a promiscuous tropism for various tissues. Moderate evolution of clinical isolates did not indicate the emergence of new HAdV-A31 subtypes in the recent years.

Novel bat adenoviruses with an extremely large E3 gene

“…Genes located between them encode membrane proteins, which may have conserved regions involved in manipulating host immune responses (Deryckere & Burgert, 1996;Hofmayer et al, 2009). These genes are not necessary for viral growth in vitro but are required for counteracting host immunity (Fessler et al, 2004).…”

A review of 65 years of human adenovirus seroprevalence

“…To our knowledge, HAdV-A31 is the only A proposed for vaccination strategy, principally because of its ability to escape the host's immune surveillance. Moreover, limited evolution of clinical isolates of HAdV-A31 indicated low probabilities for the emergence of new subtypes in the recent years [173]. Species B (including types 3,7,11,14,16,21,34,35,50,55) The species B HAdVs (which, as mentioned above are from gorillas) are subdivided into subspecies B1 (types B3, B7, B16, B21 and B50) and B2 (types B11, B14, B34, B35 and B55) based on DNA homology.…”

Adenoviromics: Mining the Human Adenovirus Species D Genome

“…The hypervariable regions in HAdV-D were found to be sharply reduced in GC nucleotide content relative to the rest of the genome (Robinson et al, 2013a ). Mutations in HAdV are relatively infrequent, with genome stability now documented in some types across decades (Hofmayer et al, 2009 ; Mahadevan et al, 2010 ; Seto et al, 2010 ; Dehghan et al, 2013b ; Robinson et al, 2013a ; Alkhalaf et al, 2015 ). However, those regions of the genome shown to be hypervariable and relatively low in GC content are the very same also shown to undergo homologous recombination (Robinson et al, 2009a , 2011b ; Walsh et al, 2009 ; Zhou et al, 2012 ; Singh et al, 2013 ), driving the evolution of new genotypes.…”