Abstract

Herpesviruses are ubiquitous double-stranded DNA viruses infecting many animals, with the capacity to cause disease in both immunocompetent and immunocompromised hosts. Different herpesviruses have different cell tropisms, and have been detected in a diverse range of tissues and sample types. Metagenomics—encompassing viromics—analyses the nucleic acid of a tissue or other sample in an unbiased manner, making few or no prior assumptions about which viruses may be present in a sample. This approach has successfully discovered a number of novel herpesviruses. Furthermore, metagenomic analysis can identify herpesviruses with high degrees of sequence divergence from known herpesviruses and does not rely upon culturing large quantities of viral material. Metagenomics has had success in two areas of herpesvirus sequencing: firstly, the discovery of novel exogenous and endogenous herpesviruses in primates, bats and cnidarians; and secondly, in characterizing large areas of the genomes of herpesviruses previously only known from small fragments, revealing unexpected diversity. This review will discuss the successes and challenges of using metagenomics to identify novel herpesviruses, and future directions within the field.

Highlights

  • Herpesviruses are double-stranded DNA viruses which infect many members of the animal kingdom, including mammals, birds and reptiles (McGeoch and Gatherer, 2005), fish (Lepa and Siwicki, 2012), amphibians (Davison et al, 2006), molluscs (Nicolas et al, 1992; Savin et al, 2010), and cnidarians (Vega Thurber et al, 2008; Grasis et al, 2014)

  • Metagenomics is the newest approach to add to this list: a deep-sequencing-based analysis of the nucleic acid contents of a cellular or acellular sample, unreliant on tissue culture and without reference to prior knowledge of which viruses are present in a sample

  • We summarize some of the success stories in identifying novel herpesviruses through metagenomics, and offer a warning on the topic of virus discovery

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Summary

Introduction

Herpesviruses are double-stranded DNA viruses which infect many members of the animal kingdom, including mammals, birds and reptiles (McGeoch and Gatherer, 2005), fish (Lepa and Siwicki, 2012), amphibians (Davison et al, 2006), molluscs (Nicolas et al, 1992; Savin et al, 2010), and cnidarians (Vega Thurber et al, 2008; Grasis et al, 2014) They typically infect a large proportion of their target population, spreading through a variety of horizontal and vertical routes. We summarize some of the success stories in identifying novel herpesviruses through metagenomics, and offer a warning on the topic of virus discovery

Finding the Needle in a Haystack
Herpesviruses Hiding in Plain Sight
Going Batty for Metagenomics
An Ocean of Herpesviruses
Novel Virus or Novel Contaminant?
Findings
Methodology Influences Success
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