NDLI: Structural variation of centromeric endogenous retroviruses in human populations and their impact on cutaneous T-cell lymphoma, Sézary syndrome, and HIV infection

Content Provider	Springer Nature : BioMed Central
Author	Kaplan, Mark H. Kaminski, Mark Estes, Judith M. Gitlin, Scott D. Zahn, Joseph Elder, James T. Tejasvi, Trilokraj Gensterblum, Elizabeth Sawalha, Amr H. McGowan, Joseph Patrick Dosik, Michael H. Direskeneli, Haner Direskeneli, Guher Saruhan Adebamowo, Sally N. Adebamowo, Clement A. Sajadi, Mohammad Contreras-Galindo, Rafael
Abstract	Background Human Endogenous Retroviruses type K HML-2 (HK2) are integrated into 117 or more areas of human chromosomal arms while two newly discovered HK2 proviruses, K111 and K222, spread extensively in pericentromeric regions, are the first retroviruses discovered in these areas of our genome. Methods We use PCR and sequencing analysis to characterize pericentromeric K111 proviruses in DNA from individuals of diverse ethnicities and patients with different diseases. Results We found that the 5′ LTR-gag region of K111 proviruses is missing in certain individuals, creating pericentromeric instability. K111 deletion (−/− K111) is seen in about 15% of Caucasian, Asian, and Middle Eastern populations; it is missing in 2.36% of African individuals, suggesting that the −/− K111 genotype originated out of Africa. As we identified the −/−K111 genotype in Cutaneous T-cell lymphoma (CTCL) cell lines, we studied whether the −/−K111 genotype is associated with CTCL. We found a significant increase in the frequency of detection of the −/−K111 genotype in Caucasian patients with severe CTCL and/or Sézary syndrome (n = 35, 37.14%), compared to healthy controls (n = 160, 15.6%) [p = 0.011]. The −/−K111 genotype was also found to vary in HIV-1 infection. Although Caucasian healthy individuals have a similar frequency of detection of the −/− K111 genotype, Caucasian HIV Long-Term Non-Progressors (LTNPs) and/or elite controllers, have significantly higher detection of the −/−K111 genotype (30.55%; n = 36) than patients who rapidly progress to AIDS (8.5%; n = 47) [p = 0.0097]. Conclusion Our data indicate that pericentromeric instability is associated with more severe CTCL and/or Sézary syndrome in Caucasians, and appears to allow T-cells to survive lysis by HIV infection. These findings also provide new understanding of human evolution, as the −/−K111 genotype appears to have arisen out of Africa and is distributed unevenly throughout the world, possibly affecting the severity of HIV in different geographic areas.
Related Links	https://bmcmedgenomics.biomedcentral.com/counter/pdf/10.1186/s12920-019-0505-8.pdf
Ending Page	18
Page Count	18
Starting Page	1
File Format	HTM / HTML
ISSN	17558794
DOI	10.1186/s12920-019-0505-8
Journal	BMC Medical Genomics
Issue Number	1
Volume Number	12
Language	English
Publisher	BioMed Central
Publisher Date	2019-05-02
Access Restriction	Open
Subject Keyword	Human Genetics Microarrays Gene Expression HERV-K K111 Pericentromeric instability Centromeres CTCL AIDS HIV
Content Type	Text
Resource Type	Article
Subject	Genetics (clinical) Genetics
Journal Impact Factor	2.1/2023
5-Year Journal Impact Factor	2.5/2023

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