Koonin EV, Dolja VV, Krupovic M, Kuhn JH. (2021) Viruses Defined by the Position of the Virosphere within the Replicator Space. Microbiol Mol Biol Rev. Sep 1:e0019320. doi: 10.1128/MMBR.00193-

All previous virus definitions were insufficient to unambiguously define viruses as they are broadly understood today. Here, we explore the boundaries of the virosphere within the virtual space of replicators and the relationships between viruses and other types of replicators. As we have demonstrated previously, viruses have evolved on many occasions from nonviral replicators, such as plasmids, by recruiting host proteins to become virion components. Conversely, other types of replicators have repeatedly evolved from viruses. Thus, the virosphere is a dynamic entity with extensive evolutionary traffic across its boundaries. We argue that the virosphere proper, here termed orthovirosphere, consists of a distinct variety of replicators that encode structural proteins encasing the replicators’ genomes, thereby facilitating transmission among hosts. Numerous and diverse replicators, such as virus-derived but capsidless RNA and DNA elements occupy the zone surrounding the orthovirosphere in the virtual replicator space. We define this zone as the perivirosphere. Although intense debates on the nature of certain replicators that adorn the internal and external boundaries of the virosphere will likely continue, we present an operational definition of virus that recently has been accepted by the International Committee on Taxonomy of Viruses.