Tales from the crypt and coral reef: the successes and challenges of identifying new herpesviruses using metagenomics

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.

Sequence analysis of malacoherpesvirus proteins: Pan-herpesvirus capsid module and replication enzymes with an ancient connection to “Megavirales”

“…Putative herpesvirus-like isolated from other aquatic Metazoa, such as two species of stony corals and wild-caught Hydra sp., have been reported (Vega Thurber et al, 2008;Grasis et al, 2014;Correa et al, 2016). Caution has been advised in interpreting these results (Houldcroft and Breuer, 2015;Wood-Charlson et al, 2015;Sweet and Bythell, 2016), and our reanalysis of the three publicly available short sequences from these studies annotated as fragments of anthozoan herpesvirus DNA suggests that they are in fact of bacterial and fungal provenance (Additional File 6). The existence of herpesviruses of coelenterates is nevertheless likely, given that particles with herpesvirus-like morphology have been observed in coral Acropora (Correa et al, 2016).…”

Clinical and biological insights from viral genome sequencing

“…The risk of incidental findings in pathogen sequencing (for example, the discovery of HIV infection during metagenomic sequencing for other pathogens) is not novel and the solution The issues of sensitivity and contamination are especially important in WGS, because of the risk of both false-negative and false-positive detection of pathogens. Highly sensitive sequencing (whether metagenomic, PCR-based or target enrichment-based) may detect low-level contaminating viral nucleic acids 112,113 . For example, murine leukaemia virus 114,115 and parvovirus-like sequences 116,117 are just two of many contaminants that can come from common laboratory reagents, such as nucleic acid extraction columns 118 .…”

Current Trends in Diagnostics of Viral Infections of Unknown Etiology

“…The risk of contamination and the issues with sensitivity are important to sequencing viral nucleic acids, because they cause false positive and false negative results, respectively. High-sensitivity sequencing (be it metagenomic, PCR-based or probe-enriched) allows for detection of minimal quantities of contaminating viral nucleic acids [208,209]. For example, murine leukemia virus (MLV) [198,210] and Parvovirus-like sequences [99,211] are only two kinds of the vast range of common contaminants found even in commercial laboratory supplies [212].…”