Endogenous Retroviruses Drive Resistance and Promotion of Exogenous Retroviral Homologs

Abstract

Endogenous retroviruses (ERVs) serve as markers of ancient viral infections and provide invaluable insight into host and viral evolution. ERVs have been exapted to assist in performing basic biological functions, including placentation, immune modulation, and oncogenesis. A subset of ERVs share high nucleotide similarity to circulating horizontally transmitted exogenous retrovirus (XRV) progenitors. In these cases, ERV–XRV interactions have been documented and include ( a) recombination to result in ERV–XRV chimeras, ( b) ERV induction of immune self-tolerance to XRV antigens, ( c) ERV antigen interference with XRV receptor binding, and ( d) interactions resulting in both enhancement and restriction of XRV infections. Whereas the mechanisms governing recombination and immune self-tolerance have been partially determined, enhancement and restriction of XRV infection are virus specific and only partially understood. This review summarizes interactions between six unique ERV–XRV pairs, highlighting important ERV biological functions and potential evolutionary histories in vertebrate hosts. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 9 is February 16, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The healthy human virome: from virus–host symbiosis to disease

“…Over 3,000 of human endogenous retroviruses (HERVs) are integrated into the host genome, comprising about 8% of human DNA [38]. Accordingly, the HERVs play important and diverse roles in human biology that cannot be discussed in this brief review in any detail (for recent reviews, see [39][40][41][42]). Most of the HERVs appear to descend from ancient integration events so that the virus genes are disrupted and rearranged.…”

A natural laboratory to elucidate the evolution of endogenous‐exogenous retroviral interactions

“…In addition to KoRV, there are five other known endogenous retroviruses with existing exogenous homologs (Chiu and VandeWoude, 2020a). In all cases, interactions between the couplets have been documented including recombination, receptor interference, negative selection of the adaptive immune response, and promotion and restriction of infection via various mechanisms (Figure 1; Chiu and VandeWoude, 2020a).…”

“…In addition to KoRV, there are five other known endogenous retroviruses with existing exogenous homologs (Chiu and VandeWoude, 2020a). In all cases, interactions between the couplets have been documented including recombination, receptor interference, negative selection of the adaptive immune response, and promotion and restriction of infection via various mechanisms (Figure 1; Chiu and VandeWoude, 2020a). For example, endogenous feline leukemia virus (enFeLV) appears to be protective against exogenous FeLV infection, both in natural infections and in cell culture, though the mechanism has yet been fully resolved.…”

“…The extent of interactions between enKoRV and exogenous KoRV remains unknown and the opportunity exists to observe interactions as they evolve. Figure adapted from Yu et al (2019) graphical abstract and Chiu and VandeWoude (2020a, figure 1)…”

Analysis of Simian Endogenous Retrovirus (SERV) proviruses in Old World Monkey Genomes: Evidence for a Transition to Replication during Embryogenesis

“…Undeniably, such processes are of great value when studying the reshaping of genomes, but an, often forgotten, aspect of EVEs is the information that captured viral sequences can give us about the deep history of the viruses themselves. By now it has been firmly recognized that EVEs are derived from viruses that were once infectious, in fact, endogenization of exogenous retroviruses can be seen in action in several species, for instance murine leukemia virus (MLV) in mice, feline leukemia virus in cats and koala retrovirus in koala's (for an overview, see: [1]). Likewise, many viruses, and especially retroviruses, where chromosomal integration is an essential part of their lifecycle, have entered the mammalian germ line in the past, some being more successful in doing so than others (for a review, see: [2]).…”