Unraveling the viral dark matter through viral metagenomics

Abstract

Viruses are part of the microbiome and have essential roles in immunology, evolution, biogeochemical cycles, health, and disease progression. Viruses influence a wide variety of systems and processes, and the continued discovery of novel viruses is anticipated to reveal new mechanisms influencing the biology of diverse environments. While the identity and roles of viruses continue to be discovered and understood through viral metagenomics, most of the sequences in virome datasets cannot be attributed to known viruses or may be only distantly related to species already described in public sequence databases, at best. Such viruses are known as the viral dark matter. Ongoing discoveries from the viral dark matter have provided insights into novel viruses from a variety of environments, as well as their potential in immunological processes, virus evolution, health, disease, therapeutics, and surveillance. Increased understanding of the viral dark matter will continue with a combination of cultivation, microscopy, sequencing, and bioinformatic efforts, which are discussed in the present review.

Keywords: crAssphage; dark matter; microbiome; phage; virome; virus discovery.

Figure 1

Several roles of viruses. Viruses are known to be involved in genome evolution (A), host cell lysis, which may promote health or disease (B), and biogeochemical cycles (C).

Figure 2

Overview of important viral metagenomic or virome studies landmarks between 2012-2022. Expanded from (28).

Figure 3

Diagram demonstrating potential applications of the viral dark matter in health, disease, therapeutics, and surveillance. Potential expected and unexpected sources of new viruses (i.e., animal, and environmental) that could contribute to the viral dark matter are also shown.