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endogenous retrovirus

Retroviruses are RNA viruses that make DNA copies of themselves & integrate into the DNA of hosts they infect. Etiology: - endogenous retroviruses are relics of ancient infections that affected the primate germ line in the last 100 million years [3] Epidemiology: - about 8% of the human genome is composed of these ancient retroviral genes - apparently they cannot reform the retroviruses from which they came Function: - it had been generally assumed they are simply evolutionary detritus without role in physiology or pathogenesis of disease - endogenous retroviruses may play a role in the innate immune response [3] Structure: - LTR-MA-CA-NC-PR-RT-IN-SU-TM-LTR where: - LTR is long-terminal repeat (5') - MA is gag matrix - NC is nucleocapsid - PR is pro-pol protease - RT is reverse transcriptase - IN is integrase - SU is env surface - TM is transmembrane - LTR is long-terminal repeat (3') Pathology: - activation or unsilencing of certain retroviral genes in B lymphocytes may play a role in a) Hodgkin's disease b) anaplastic large cell lymphoma - CSF1R transcription in transformed B cells activates aberrant expression of retroviral long-terminal repeat (LTR) THE1B - LTR-THE1B expression occurs with loss of expression of corepressor CBFA2T3 [2] - primate-specific endogenous retroviruses are a source of enhancers with cancer-specific activity [4] - in epithelial tumors including colorectal cancer, oncogenic MAPK/AP1 signaling drives activation of enhancers derived from the primate-specific endogenous retrovirus family LTR10 [4] - in vitro, LTR10 elements of colorectal cancer cells regulate tumor-specific expression of genes associated with tumorigenesis, including ATG12 & XRCC4 [4] - in vivo, LTR10 elements exhibit germline & somatic structural variation resulting from a highly mutable internal tandem repeat region affecting AP1 binding [4] Comparative biology: - in the mouse, endogenous provirus DNA comprises up to 0.4% of the genome

Specific

endogenous retrovirus 1 endogenous retrovirus 3

General

Retroviridae (retrovirus)

Properties

KINGDOM: virus GENOME-TYPE: ribonucleic acid

Database Correlations

OMIM 131170

References

  1. Mendelian Inheritance in Man 1990 MIM#131170
  2. Lamprecht B et al Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma. Nat Med 2010 May; 16:571. PMID: 20436485 - Engel ME and Hiebert SW. The enemy within: Dormant retroviruses awaken. Nat Med 2010 May; 16:517. PMID: 20448571
  3. Grandi N, Tramontano E. Human Endogenous Retroviruses Are Ancient Acquired Elements Still Shaping Innate Immune Responses. Frontiers in Immunology, 2018. Sept 10 PMID: 30250470 PMCID: PMC6139349 Free PMC article
  4. Santora T Ancient Viruses in Our DNA Hold Clues to Cancer Treatment. Medscape. July 29, 2024 https://www.medscape.com/viewarticle/ancient-viruses-our-dna-hold-clues-cancer-treatment-2024a1000dtv - Ivancevic A, Simpson DM, Joyner OM et al Endogenous retroviruses mediate transcriptional rewiring in response to oncogenic signaling in colorectal cancer. Sci Adv. 2024 Jul 19;10(29):eado1218. PMID: 39018396 PMCID: PMC466953 Free PMC article.
  5. Blomberg J, Ushameckis D, Jern P Evolutionary Aspects of Human Endogenous Retroviral Sequences (HERVs) and Disease Madame Curie Bioscience Database [Internet]. NCBI Bookshelf. NBK6235 https://www.ncbi.nlm.nih.gov/books/NBK6235/
  6. Jakobsson J, Vincendeau M. SnapShot: Human endogenous retroviruses. Cell. 2022 Jan 20;185(2):400-400.e1. PMID: 35063077 Free article. https://www.cell.com/action/showPdf?pii=S0092-8674%2821%2901491-4
  7. Song Y, Li X, Wei X, Cui J. Human Endogenous Retroviruses as Biomedicine Markers. Virol Sin. 2021 Oct;36(5):852-858. PMID: 33905075 PMCID: PMC8558139 Free PMC article. Review.
  8. Kitsou K, Lagiou P, Magiorkinis G. Human endogenous retroviruses in cancer: Oncogenesis mechanisms and clinical implications. J Med Virol. 2023 Jan;95(1):e28350. PMID: 36428242 PMCID: PMC10108094 Free PMC article. Review.