Molecular Evolution of Human Adenovirus (HAdV) Species C

Akshay Dhingra,Jörg Hofmann,Tina Ganzenmueller,Thomas Dobner,Patrick Obermeier,Fabian Hausmann,Klaus Hamprecht,Elias Hage,Barbara Rath,Albert Heim,Sindy Böttcher

doi:10.1038/s41598-018-37249-4

Abstract

Currently, 88 different Human Adenovirus (HAdV) types are grouped into seven HAdV species A to G. Most types (57) belong to species HAdV-D. Recombination between capsid genes (hexon, penton and fiber) is the main factor contributing to the diversity in species HAdV-D. Noteworthy, species HAdV-C contains so far only five types, although species HAdV-C is highly prevalent and clinically significant in immunosuppressed patients. Therefore, the evolution of species HAdV-C was studied by generating 51 complete genome sequences from circulating strains. Clustering of the whole genome HAdV-C sequences confirmed classical typing results (fifteen HAdV-C1, thirty HAdV-C2, four HAdV-C5, two HAdV-C6). However, two HAdV-C2 strains had a novel penton base sequence and thus were re-labeled as the novel type HAdV-C89. Fiber and early gene region 3 (E3) sequences clustered always with the corresponding prototype sequence but clustering of the E4 region indicated recombination events in 26 out of the 51 sequenced specimens. Recombination of the E1 gene region was detected in 16 circulating strains. As early gene region sequences are not considered in the type definition of HAdVs, evolution of HAdV-C remains on the subtype level. Nonetheless, recombination of the E1 and E4 gene regions may influence the virulence of HAdV-C strains.

Highlights

Human adenoviruses (HAdVs) are double-stranded, non-enveloped, linear DNA viruses of 34–36 kbp length[1,2]
Nucleic acid sequences coding for the neutralization determinant of types HAdV-C1, -C2 and -C6 were highly conserved, whereas these sequences were found to be more diverse in HAdV-C5 strains
Analysis of the complete genomes of 51 circulating species HAdV-C strains revealed multiple recombination events of early gene regions (e.g. E1 and E4) that may contribute to the evolution of species HAdV-C

Summary

Introduction

Human adenoviruses (HAdVs) are double-stranded, non-enveloped, linear DNA viruses of 34–36 kbp length[1,2]. Rapid selection of novel capsid gene sequences is the major factor for diversity in species HAdV-B1,3,5,6, a few recombinant HAdV types of species B have been described[7]. Infections with species HAdV-C types are highly prevalent, evolution of species HAdV-C did not results in multiple novel types, neither by recombination between the main capsid genes nor by rapid selection of e.g. immune escape mutations in the highly variable immunogenic loops of hexon. A recent study applying whole genomic sequencing to adenovirus specimens from immunocompromised pediatric patients confirmed the predominance of species HAdV-C strains in this population and detected an infection chain (transmission of HAdV-A31 between the included patients)[22]

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