Viral metagenomics: are we missing the giants?

Amoeba-infecting giant viruses are recently discovered viruses that have been isolated from diverse environments all around the world. In parallel to isolation efforts, metagenomics confirmed their worldwide distribution from a broad range of environmental and host-associated samples, including humans, depicting them as a major component of eukaryotic viruses in nature and a possible resident of the human/animal virome whose role is still unclear. Nevertheless, metagenomics data about amoeba-infecting giant viruses still remain scarce, mainly because of methodological limitations. Efforts should be pursued both at the metagenomic sample preparation level and on in silico analyses to better understand their roles in the environment and in human/animal health and disease.