Endogenous feline leukemia virus long terminal repeat integration site diversity is highly variable in related and unrelated domestic cats

Retrovirology. 2024 Feb 12;21(1):3. doi: 10.1186/s12977-024-00635-0.

Abstract

Endogenous retroviruses (ERV) are indicators of vertebrate evolutionary history and play important roles as homeostatic regulators. ERV long terminal repeat (LTR) elements may act as cis-activating promoters or trans-activating enhancer elements modifying gene transcription distant from LTR insertion sites. We previously documented that endogenous feline leukemia virus (FeLV)-LTR copy number variation in individual cats tracks inversely with susceptibility to virulent FeLV disease. To evaluate FeLV-LTR insertion characteristics, we assessed enFeLV-LTR integration site diversity in 20 cats from three genetically distinct populations using a baited linker-mediated PCR approach. We documented 765 individual integration sites unequally represented among individuals. Only three LTR integration sites were shared among all individuals, while 412 sites were unique to a single individual. When primary fibroblast cultures were challenged with exogenous FeLV, we found significantly increased expression of both exogenous and endogenous FeLV orthologs, supporting previous findings of potential exFeLV-enFeLV interactions; however, viral challenge did not elicit transcriptional changes in genes associated with the vast majority of integration sites. This study assesses FeLV-LTR integration sites in individual animals, providing unique transposome genotypes. Further, we document substantial individual variation in LTR integration site locations, even in a highly inbred population, and provide a framework for understanding potential endogenous retroviral element position influence on host gene transcription.

Keywords: Endogenous retrovirus; Feline leukemia virus; Functional genomics; Integration sites.

MeSH terms

  • Animals
  • Cats
  • DNA Copy Number Variations
  • Endogenous Retroviruses* / genetics
  • Humans
  • Leukemia Virus, Feline / genetics
  • Leukemia Virus, Feline / metabolism
  • Leukemia, Feline* / genetics
  • Promoter Regions, Genetic
  • Terminal Repeat Sequences