Human endogenous retrovirus K

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Human endogenous retrovirus K
Virus classification Edit this classification
(unranked): Virus
Realm: Riboviria
Kingdom: Pararnavirae
Phylum: Artverviricota
Class: Revtraviricetes
Order: Ortervirales
Family: Retroviridae
Genus: Betaretrovirus (?)
(unranked): Human endogenous retrovirus K

Human endogenous retrovirus K (HERV-K) or Human teratocarcinoma-derived virus (HDTV) is a family of human endogenous retroviruses associated with malignant tumors of the testes.[1][2][3][4] Phylogenetically, the HERV-K group belongs to the ERV2 or Class II or Betaretrovirus-like supergroup.[5] Over the past several years, it has been found that this group of ERVs play an important role in embryogenesis, but their expression is silenced in most cell types in healthy adults.[6] The HERV-K family, and particularly its subgroup HML-2, is the youngest and most transcriptionally active group and hence, it is the best studied among other ERVs. Reactivation of it or anomalous expression of HML-2 in adult tissues has been associated with various types of cancer [7][8][9] and with neurodegenerative diseases such as amytrophic lateral sclerosis (ALS).[10][5] Endogenous retrovirus K (HERV-K) is related to mammary tumor virus in mice. It exists in the human and cercopithecoid genomes. Human genome contains hundreds of copies of HERV-K and many of them possess complete open reading frames (ORFs) that are transcribed and translated, especially in early embryogenesis and in malignancies.[5][11] One notable[12][13][14][15] location of HERV-K is the C4 gene of RCCX module.[16][17] HERV-K is also found in apes and Old World monkeys. It is uncertain how long ago in primate evolution the full-length HERV-K proviruses which are in the human genome today were created.[18]

The human endogenous retrovirus K (HERV-K) was inherited million years ago by the genome of the human ancestors.[18] In 1999 Barbulescu, et al. showed that, of ten HERV-K proviruses cloned, eight were unique to humans, while one was shared with chimpanzees and bonobos, and one with chimpanzees, bonobos and gorillas.[19] Originally, HERV-K was observed by low-stringency hybridization with probes for the mammary tumor virus of the mouse and A particle intracutaneous mouse.[18]

In 2015 Grow et al. demonstrated that HERV-K is transcribed during embryogenesis from the eight cell stage up to the stem cell derivation.[20] Furthermore, overexpression of the HERV-K accessory protein Rec (regulator of expression encoded by corf; Pfam PF15695) increases IFITM1 levels on the cell surface and inhibits viral infection.[20][21] HERV-K is called, phylogenetically, a supergroup of viruses. It is the only group that reported to contain human-specific members of endogenous retroviruses (ERVs).[22]

HERV-K is receptive to microenvironmental modifications and melanoma cells are closely correlated with epigenetic and microenvironmental anomalies. Also the association of HERV-K activation with carcinogenesis is especially interesting.[23]

See also[edit]


  1. ^ Boeke JD, Stoye JP (1997). "Retrotransposons, endogenous retroviruses, and the evolution of retroelements". In JM Coffin, SH Hughes, HE Varmus (eds.). Retroviruses. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press. pp. 343–435. PMID 21433351.
  2. ^ Boller K, König H, Sauter M, Mueller-Lantzsch N, Löwer R, Löwer J, Kurth R (September 1993). "Evidence That HERV-K Is the Endogenous Retrovirus Sequence That Codes for the Human Teratocarcinoma-Derived Retrovirus HTDV". Virology. 196 (1): 349–353. doi:10.1006/viro.1993.1487. PMID 8356806.
  3. ^ Löwer J, Wondrak EM, Kurth R (November 1987). "Genome analysis and reverse transcriptase activity of human teratocarcinoma-derived retroviruses". The Journal of General Virology. 68 (11): 2807–15. doi:10.1099/0022-1317-68-11-2807. PMID 2445905.
  4. ^ Rédei GP (2008). Encyclopedia of genetics, genomics, proteomics, and informatics (3rd ed.). Springer. ISBN 978-1-4020-6754-9.
  5. ^ a b c Garcia-Montojo M, Doucet-O'Hare T, Henderson L, Nath A (14 October 2018). "Human endogenous retrovirus-K (HML-2): a comprehensive review". Critical Reviews in Microbiology. 44 (6): 715–738. doi:10.1080/1040841X.2018.1501345. PMC 6342650. PMID 30318978.
  6. ^ Grow EJ, Flynn RA, Chavez SL, Bayless NL, Wossidlo M, Wesche DJ, Martin L, Ware CB, Blish CA, Chang HY, Reijo Pera RA, Wysocka J (20 April 2015). "Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells". Nature. 522 (7555): 221–225. Bibcode:2015Natur.522..221G. doi:10.1038/nature14308. PMC 4503379. PMID 25896322.
  7. ^ Argaw-Denboba A, Balestrieri E, Serafino A, Cipriani C, Bucci I, Sorrentino R, Sciamanna I, Gambacurta A, Sinibaldi-Vallebona P, Matteucci C (26 January 2017). "HERV-K activation is strictly required to sustain CD133+ melanoma cells with stemness features". Journal of Experimental & Clinical Cancer Research. 36 (1): 20. doi:10.1186/s13046-016-0485-x. PMC 5270369. PMID 28125999.
  8. ^ Cegolon L, Salata C, Weiderpass E, Vineis P, Palù G, Mastrangelo G (3 January 2013). "Human endogenous retroviruses and cancer prevention: evidence and prospects". BMC Cancer. 13 (1): 4. doi:10.1186/1471-2407-13-4. PMC 3557136. PMID 23282240.
  9. ^ Agoni L, Lenz J, Guha C, Belshaw R (18 October 2013). "Variant Splicing and Influence of Ionizing Radiation on Human Endogenous Retrovirus K (HERV-K) Transcripts in Cancer Cell Lines". PLOS ONE. 8 (10): e76472. Bibcode:2013PLoSO...876472A. doi:10.1371/journal.pone.0076472. PMC 3799738. PMID 24204631.
  10. ^ Li W, Lee MH, Henderson L, Tyagi R, Bachani M, Steiner J, Campanac E, Hoffman DA, von Geldern G, Johnson K, Maric D, Morris HD, Lentz M, Pak K, Mammen A, Ostrow L, Rothstein J, Nath A (30 September 2015). "Human endogenous retrovirus-K contributes to motor neuron disease". Science Translational Medicine. 7 (307): 307ra153. doi:10.1126/scitranslmed.aac8201. PMC 6344353. PMID 26424568.
  11. ^ Wildschutte JH, Williams ZH, Montesion M, Subramanian RP, Kidd JM, Coffin JM (19 April 2016). "Discovery of unfixed endogenous retrovirus insertions in diverse human populations". Proceedings of the National Academy of Sciences. 113 (16): E2326–E2334. Bibcode:2016PNAS..113E2326W. doi:10.1073/pnas.1602336113. PMC 4843416. PMID 27001843.
  12. ^ Severance EG, Leister F, Lea A, Yang S, Dickerson F, Yolken RH (August 2021). "Complement C4 associations with altered microbial biomarkers exemplify gene-by-environment interactions in schizophrenia". Schizophr Res. 234: 87–93. doi:10.1016/j.schres.2021.02.001. PMC 8373622. PMID 33632634.
  13. ^ Margery-Muir AA, Bundell C, Wetherall JD, Whidborne R, Martinez P, Groth DM (September 2018). "Insights on the relationship between complement component C4 serum concentrations and C4 gene copy numbers in a Western Australian systemic lupus erythematosus cohort". Lupus. 27 (10): 1687–1696. doi:10.1177/0961203318787039. PMID 30041577. S2CID 51715884.
  14. ^ Tsang-A-Sjoe MW, Bultink IE, Korswagen LA, van der Horst A, Rensink I, de Boer M, Hamann D, Voskuyl AE, Wouters D (December 2017). "Comprehensive approach to study complement C4 in systemic lupus erythematosus: Gene polymorphisms, protein levels and functional activity". Mol Immunol. 92: 125–131. doi:10.1016/j.molimm.2017.10.004. PMID 29080553. S2CID 10363726.
  15. ^ Mason MJ, Speake C, Gersuk VH, Nguyen QA, O'Brien KK, Odegard JM, Buckner JH, Greenbaum CJ, Chaussabel D, Nepom GT (May 2014). "Low HERV-K(C4) copy number is associated with type 1 diabetes". Diabetes. 63 (5): 1789–95. doi:10.2337/db13-1382. PMID 24430436.
  16. ^ Dangel AW, Mendoza AR, Baker BJ, Daniel CM, Carroll MC, Wu LC, Yu CY (1994). "The dichotomous size variation of human complement C4 genes is mediated by a novel family of endogenous retroviruses, which also establishes species-specific genomic patterns among Old World primates". Immunogenetics. 40 (6): 425–36. doi:10.1007/BF00177825. PMID 7545960. S2CID 19796359.
  17. ^ Kerick M, Acosta-Herrera M, Simeón-Aznar CP, Callejas JL, Assassi S, Proudman SM, Nikpour M, Hunzelmann N, Moroncini G, de Vries-Bouwstra JK, Orozco G, Barton A, Herrick AL, Terao C, Allanore Y, Fonseca C, Alarcón-Riquelme ME, Radstake TR, Beretta L, Denton CP, Mayes MD, Martin J (October 2022). "Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis". npj Genom Med. 7 (1): 57. doi:10.1038/s41525-022-00327-8. PMC 9534873. PMID 36198672.
  18. ^ a b c M. Barbulescu, G. Turner, M. I. Seaman, A. S. Deinard, K. K. Kidd, ve J. Lenz, "Many human endogenous retrovirus K (HERV-K) proviruses are unique to humans", Curr. Biol., c. 9, sy 16, ss. 861-S1, Ağu. 1999, doi: 10.1016/S0960-9822(99)80390-X.
  19. ^ Madalina Barbulescu, Geoffrey Turner, Michael I. Seaman†, Amos S. Deinard‡§, Kenneth K. Kidd, Jack Lenz (1999). "Many human endogenous retrovirus K (HERV-K) proviruses are unique to humans". Current Biology. 9 (16): 861–8. Bibcode:1999CBio....9..861B. doi:10.1016/s0960-9822(99)80390-x. PMID 10469592.
  20. ^ a b Edward J. Grow, Ryan A. Flynn, Shawn L. Chavez, Nicholas L. Bayless, Mark Wossidlo, Daniel J. Wesche, Lance Martin, Carol B. Ware, Catherine A. Blish, Howard Y. Chang, Renee A. Reijo Pera, Joanna Wysocka (11 June 2015). "Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells". Nature. 522 (7555): 221–5. Bibcode:2015Natur.522..221G. doi:10.1038/nature14308. PMC 4503379. PMID 25896322.
  21. ^ Hanke K, Hohn O, Bannert N (January–February 2016). "HERV-K(HML-2), a seemingly silent subtenant – but still waters run deep". APMIS. 124 (1–2): 67–87. doi:10.1111/apm.12475. PMID 26818263.
  22. ^ M. Garcia-Montojo, T. Doucet-O'Hare, L. Henderson, ve A. Nath, "Human endogenous retrovirus-K (HML-2): a comprehensive review", Crit. Rev. Microbiol., c. 44, sy 6, ss. 715-738, Kas. 2018, doi: 10.1080/1040841X.2018.1501345.
  23. ^ E. Balestrieri vd., "Human Endogenous Retrovirus K in the Crosstalk Between Cancer Cells Microenvironment and Plasticity: A New Perspective for Combination Therapy", Front. Microbiol., c. 9, 2018, doi:10.3389/fmicb.2018.01448.

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