Human endogenous retrovirus K

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Human endogenous retrovirus K
a-c)Morphology of VLPs released from MVA-HERV-Kcon infected cells
Virus classification e
(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) 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] 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.[12]

The human endogenous retrovirus K (HERV-K) was inherited million years ago by the genome of the human ancestors.[12] 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.[13] Originally, HERV-K was observed by low-stringency hybridization with probes for the mammary tumor virus of the mouse and A particle intracutaneous mouse.[12]

HERV-K (HML-2) and its relationship to disease[14]

In 2015 Grow et al. demonstrated that HERV-K is transcribed during embryogenesis from the eight cell stage up to the stem cell derivation.[15] 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.[15][16] 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).[17]

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.[18]

See also


  1. Boeke JD, Stoye JP (1997). JM Coffin; SH Hughes; HE Varmus (eds.). Retrotransposons, endogenous retroviruses, and the evolution of retroelements. Retroviruses. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press. pp. 343–435. PMID 21433351.
  2. Boller, Klaus; König, Herbert; Sauter, Marlies; Mueller-Lantzsch, Nikolaus; Löwer, Roswitha; Löwer, Johannes; Kurth, Reinhard (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, George P. (2008). Encyclopedia of genetics, genomics, proteomics, and informatics (3rd ed.). Springer. ISBN 978-1-4020-6754-9.
  5. 5.0 5.1 5.2 Garcia-Montojo, Marta; Doucet-O’Hare, Tara; Henderson, Lisa; Nath, Avindra (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, Edward J.; Flynn, Ryan A.; Chavez, Shawn L.; Bayless, Nicholas L.; Wossidlo, Mark; Wesche, Daniel J.; Martin, Lance; Ware, Carol B.; Blish, Catherine A.; Chang, Howard Y.; Reijo Pera, Renee A.; Wysocka, Joanna (20 April 2015). "Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells". Nature. 522 (7555): 221–225. doi:10.1038/nature14308. PMC 4503379. PMID 25896322.
  7. Argaw-Denboba, Ayele; Balestrieri, Emanuela; Serafino, Annalucia; Cipriani, Chiara; Bucci, Ilaria; Sorrentino, Roberta; Sciamanna, Ilaria; Gambacurta, Alessandra; Sinibaldi-Vallebona, Paola; Matteucci, Claudia (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, Luca; Salata, Cristiano; Weiderpass, Elisabete; Vineis, Paolo; Palù, Giorgio; Mastrangelo, Giuseppe (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, Lorenzo; Lenz, Jack; Guha, Chandan; Belshaw, Robert (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. doi:10.1371/journal.pone.0076472. PMC 3799738. PMID 24204631.
  10. Li, Wenxue; Lee, Myoung-Hwa; Henderson, Lisa; Tyagi, Richa; Bachani, Muzna; Steiner, Joseph; Campanac, Emilie; Hoffman, Dax A.; von Geldern, Gloria; Johnson, Kory; Maric, Dragan; Morris, H. Douglas; Lentz, Margaret; Pak, Katherine; Mammen, Andrew; Ostrow, Lyle; Rothstein, Jeffrey; Nath, Avindra (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, Julia Halo; Williams, Zachary H.; Montesion, Meagan; Subramanian, Ravi P.; Kidd, Jeffrey M.; Coffin, John M. (19 April 2016). "Discovery of unfixed endogenous retrovirus insertions in diverse human populations". Proceedings of the National Academy of Sciences. 113 (16): E2326–E2334. doi:10.1073/pnas.1602336113. PMC 4843416. PMID 27001843.
  12. 12.0 12.1 12.2 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.
  13. 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. doi:10.1016/s0960-9822(99)80390-x. PMID 10469592.
  14. Shin, Wonseok; Mun, Seyoung; Han, Kyudong (December 2023). "Human Endogenous Retrovirus-K (HML-2)-Related Genetic Variation: Human Genome Diversity and Disease". Genes. 14 (12): 2150. doi:10.3390/genes14122150. ISSN 2073-4425.
  15. 15.0 15.1 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.
  16. 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.
  17. 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.
  18. 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.

Further reading