Beyond pathogens: the intriguing genetic legacy of endogenous retroviruses in host physiology

Front Cell Infect Microbiol. 2024 Apr 9:14:1379962. doi: 10.3389/fcimb.2024.1379962. eCollection 2024.

Abstract

The notion that viruses played a crucial role in the evolution of life is not a new concept. However, more recent insights suggest that this perception might be even more expansive, highlighting the ongoing impact of viruses on host evolution. Endogenous retroviruses (ERVs) are considered genomic remnants of ancient viral infections acquired throughout vertebrate evolution. Their exogenous counterparts once infected the host's germline cells, eventually leading to the permanent endogenization of their respective proviruses. The success of ERV colonization is evident so that it constitutes 8% of the human genome. Emerging genomic studies indicate that endogenous retroviruses are not merely remnants of past infections but rather play a corollary role, despite not fully understood, in host genetic regulation. This review presents some evidence supporting the crucial role of endogenous retroviruses in regulating host genetics. We explore the involvement of human ERVs (HERVs) in key physiological processes, from their precise and orchestrated activities during cellular differentiation and pluripotency to their contributions to aging and cellular senescence. Additionally, we discuss the costs associated with hosting a substantial amount of preserved viral genetic material.

Keywords: endogenous retroviruses; genetic regulation; inflammaging; inflammatory diseases; transactivation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cellular Senescence / genetics
  • Endogenous Retroviruses* / genetics
  • Endogenous Retroviruses* / physiology
  • Evolution, Molecular
  • Host Microbial Interactions / genetics
  • Host-Pathogen Interactions / genetics
  • Humans
  • Proviruses / genetics
  • Proviruses / physiology
  • Retroviridae Infections / virology

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. CR is granted by Fundação de Amparo à pesquisa do Estado de São Paulo (FAPESP) Grants #2015/05958-3 and #2022/10408-6. LN is granted by Fundação de Amparo à pesquisa do Estado de São Paulo (FAPESP) Grants #2013/24223-9 and #2023/08773-0