Genomic analysis of a large set of currently—and historically—important human adenovirus pathogens

Ashrafali Mohamed Ismail ,Tiange Cui,Kalpana Dommaraju,Gurdeep Singh,Shoaleh Dehghan,Jason Seto,Susmita Shrivastava,Nadia Fedorova ,Rebecca Halpin ,Mary Smith Mccrory Jones ,Leonardo Ferreyra ,H N Madhavan ,K Lily Therese ,Neha Gupta,Timothy B Stockwell,Ramana Madupu,Albert Heim,Adriana E Kajon,Eric G Romanowski,Regis P Kowalski,Jambulingam Malathi,Qiwei Zhang,Jaya Rajaiya,David W Dyer,James Chodosh,Donald Seto

doi:10.1038/s41426-017-0004-y

Abstract

Human adenoviruses (HAdVs) are uniquely important “model organisms” as they have been used to elucidate fundamental biological processes, are recognized as complex pathogens, and are used as remedies for human health. As pathogens, HAdVs may effect asymptomatic or mild and severe symptomatic disease upon their infection of respiratory, ocular, gastrointestinal, and genitourinary systems. High-resolution genomic data have enhanced the understanding of HAdV epidemiology, with recombination recognized as an important and major pathway in the molecular evolution and genesis of emergent HAdV pathogens. To support this view and to actualize an algorithm for identifying, characterizing, and typing novel HAdVs, we determined the DNA sequence of 95 isolates from archives containing historically important pathogens and collections housing currently circulating strains to be sequenced. Of the 85 samples that were completely sequenced, 18 novel recombinants within species HAdV-B and D were identified. Two HAdV-D genomes were found to contain novel penton base and fiber genes with significant divergence from known molecular types. In this data set, we found additional isolates of HAdV-D53 and HAdV-D58, two novel genotypes recognized recently using genomics. This supports the thesis that novel HAdV genotypes are not limited to “one-time” appearances of the prototype but are of importance in HAdV epidemiology. These data underscore the significance of lateral genomic transfer in HAdV evolution and reinforce the potential public health impact of novel genotypes of HAdVs emerging in the population.

Highlights

Human adenoviruses (HAdVs) occupy an important unique niche in biology and medicine as they were among the first respiratory viral pathogens to be isolated, identified, and characterized, but were model organisms for fundamental discoveries and insights into molecular and cellular biology, immunology, and systems biology
A wide spectrum of diseases is associated with HAdVs, involving the respiratory, ocular, gastrointestinal, and genitourinary systems, as well as a metabolic disorder[7]
HAdV-A, -B, and -C are all associated with infections of allogenic transplant recipients[7], while many novel types within HAdV-D were first identified in patients with AIDS13 and other immunocompromised patients as potential opportunistic pathogens[14]

Summary

Introduction

Human adenoviruses (HAdVs) occupy an important unique niche in biology and medicine as they were among the first respiratory viral pathogens to be isolated, identified, and characterized, but were model organisms for fundamental discoveries and insights into molecular and cellular biology, immunology, and systems biology These include messenger RNA splicing[1], eukaryotic DNA replication[2], and antigen presentation to T-cells[3]. A wide spectrum of diseases is associated with HAdVs, involving the respiratory, ocular, gastrointestinal, and genitourinary systems, as well as a metabolic disorder (obesity)[7] These have been documented extensively in the literature and many pathogenic strains have been collected into archives. HAdV is a major public health concern in both immunocompetent and immunocompromised individuals

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