Adenoviromics: Mining the Human Adenovirus Species D Genome.

Ashrafali M Ismail,David W Dyer,Jeong Yoon Lee,Donald Seto,Gurdeep Singh,James Chodosh,Ji Sun Lee,Jaya Rajaiya

doi:10.3389/fmicb.2018.02178

Abstract

Human adenovirus (HAdV) infections cause disease world-wide. Whole genome sequencing has now distinguished 90 distinct genotypes in 7 species (A-G). Over half of these 90 HAdVs fall within species D, with essentially all of the HAdV-D whole genome sequences generated in the last decade. Herein, we describe recent new findings made possible by mining of this expanded genome database, and propose future directions to elucidate new functional elements and new functions for previously known viral components.

Highlights

Human adenovirus (HAdV) infections represent a significant source of morbidity and mortality, world-wide and at all ages, through highly transmittable infections at mucosal sites, including the eye, and urinary, respiratory, and gastrointestinal tracts (Horwitz, 1996)
HAdVs are divided phylogenetically into seven species (A-G), with a total of 90 recognized genotypes with whole genome sequences in GenBank, including the original 51 “serotypes”—determined by serum neutralization—which all have been fully sequenced (Table 1) (Robinson et al, 2013a) Human adenovirus species D (HAdV-D) is the largest and most rapidly growing among all HAdV species, and contains viruses associated with epidemic keratoconjunctivitis (EKC), a severe, hyperacute ocular surface infection (Butt and Chodosh, 2006)
A collaboration funded by the American Recovery and Reinvestment Act of 2009 came to fruition with the complete whole genome sequencing and analysis of all previously unsequenced HAdV-D serotypes (Robinson et al, 2013a), leading to a new understanding of adenovirus ontogeny (Jones et al, 2007; Robinson et al, 2008, 2009a,b; Robinson et al, 2011b,c; Robinson et al, 2013a,b; Walsh et al, 2009, 2010a,b; Arnold et al, 2010; Torres et al, 2010; Dehghan et al, 2011, 2013a,b; Walsh et al, 2011; Liu et al, 2011; Seto et al, 2011, 2013; Singh et al, 2012, 2013; Zhou et al, 2012)—including those

Summary

INTRODUCTION

Human adenovirus (HAdV) infections represent a significant source of morbidity and mortality, world-wide and at all ages, through highly transmittable infections at mucosal sites, including the eye, and urinary, respiratory, and gastrointestinal tracts (Horwitz, 1996). Human corneal epithelial cell tropism could be predicted by the presence of a lysine or alanine at residue 240, and this amino acid residue in EKC viruses showed evidence for positive selection These data added to the prior observation by Huang and coworkers that artificial mutation to a lysine at residue 240 in a non-EKC virus could confer infection of Chang cells, a conjunctiva derived continuous cell line (Huang et al, 1999). Because Chang cells came later known to be contaminated by HeLa cells, the importance of residue 240 to ocular tropism was until this new observation, in some doubt Another recently published effort provided further evidence of the importance and potential for HAdV genome mining. The authors identified a potential new leader sequence embedded within the E3 region, tentatively named the j-leader (Figure 1)

Year published

GENOMICS AND EVOLUTION

HAdV type

TRANSCRIPTION FACTOR BINDING SITES

PROTEIN INTERACTOMES

CONCLUSIONS