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Review
. 2025 Aug 15;16(8):964.
doi: 10.3390/genes16080964.

Endogenous Retroviruses in Host-Virus Coevolution: From Genomic Domestication to Functional Innovation

Ruqi Jiang  1 , Jingjun Zhou  1 , Yue Liu  1 , Guanjin Zhou  1 , Dongdong Fan  1 , Lixin Xiang  1 , Ye Chen  1 , Jianzhong Shao  1   2
Affiliations
Review

Endogenous Retroviruses in Host-Virus Coevolution: From Genomic Domestication to Functional Innovation

Ruqi Jiang et al. Genes (Basel). .

Abstract

Endogenous retroviruses (ERVs) are remnants of retroviral infections that have become stably integrated into host germline genomes. Far beyond passive genomic elements, ERVs actively shape host evolution through complex mechanisms involving genetic innovation, immune modulation, and species adaptation. This review provides a comprehensive synthesis of ERV biology, highlighting recent advances in their classification, amplification mechanisms, and epigenetic silencing. Particular emphasis is placed on the cross-talk between ERVs and exogenous retroviruses (XRVs), demonstrating how receptor competition, recombination, and immune evasion contribute to virus-host co-evolution. We explore ERVs as molecular markers for phylogenetic reconstruction, with case studies such as Koala retrovirus (KoRV) and HERV-K illustrating regional transmission dynamics and co-opted immune functions. Additionally, we discuss the functional domestication of ERVs into regulatory elements, non-coding RNAs, and envelope-derived fusion proteins that influence gene expression, antiviral defense, and placental development.

Keywords: KoRV; cross-species transmission; endogenous retrovirus; evolution; exaptation; horizontal transmission.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Endogenous replication and amplification of ERVs. (a) Autonomous retrotransposition: The retrotransposition of ERVs is mediated by the RT and IN enzymes carried by the virus itself, (b) Trans-mediated retrotransposition: The retrotransposition of ERVs is mediated by RT and IN enzymes carried by other endogenous retroviral elements present in the host genome, (c) Re-infection of ERVs: ERVs re-infect the host by forming viral particles and inserting ERV sequences at new loci.
Figure 2
Figure 2
Exaptation of ERVs. LTRs can serve as transcription factor binding sites, promoters, or enhancers to regulate the expression of target genes; ERV-derived env genes can mediate immune interference by competitively occupying viral receptors; ERV-derived nucleic acid products are sensed by pattern recognition receptors such as RIG-I and MDA5, ultimately inducing the expression of IFN-β and a range of interferon-stimulated genes (ISGs); Syncytin-1/2 promote the fusion of trophoblast cells through their fusogenic activity, leading to the formation of multinucleated syncytiotrophoblasts.
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