An Ecological Framework of the Human Virome Provides Classification of Current Knowledge and Identifies Areas of Forthcoming Discovery

Parker, Michael T.

Endogenous retroelements (EREs) represent a unique class of human-colonizing viral material that is resident in the germ line and include endogenous retroviruses (ERVs), retrotransposons, and retrotranscripts [60] . While the general classification of these genetic elements will be defined in this work as mutualistic (see The Mutualistic Virome, below), it is evident from a number of studies that they can sometimes contribute to pathogenesis. In the autoimmune disease Multiple Sclerosis (MS), human endogenous retrovirus (HERV) syncytin expression is upregulated in lesions and leads to an increase of cellular protein oxidation and destruction of oligodendrocytes [61] . Another possible autoimmune contribution of EREs is by their engagement of nucleic acid pattern recognition and downstream immune activation during both their RNA and cDNA synthesis [62, 63] . Carcinogenesis may also occur, as exemplified by the Rec protein of HERV-K(HML2), which can facilitate tumorigenesis when expressed in mice [64] . A final example of deleterious consequences conferred by EREs is their ability to destabilize the genome via insertion, rearrangement, and deletion [65] . Continued exploration is necessary to expand upon these data to elucidate the mechanisms behind the negative impacts of EREs on human health. Bacteriophages (from here, referred to as phages), which are canonically classified as commensals (see The Commensal Virome, below), may also play an atypically negative role. While these viruses do not infect human cells, the estimated 10 15 phages present in the human gut [66] and those elsewhere on the body are not likely to be completely benign. While it is known that phages can be co-opted for benefit to the host [66] , I postulate that the presence of this amount of genomic and proteinaceous material is unlikely to be immunologically inert.