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

Animals Cell Line Centromere / virology Endogenous Retroviruses / genetics Genetic Variation Genotype HIV Infections / virology Humans Lymphoma, T-Cell, Cutaneous / virology Sezary Syndrome / virology
AIDS CTCL Centromeres HERV-K HIV K111 Pericentromeric instability

Journal

BMC medical genomics
ISSN: 1755-8794
Titre abrégé: BMC Med Genomics
Pays: England
ID NLM: 101319628

Informations de publication

Date de publication:
02 05 2019
Historique:
received: 01 11 2018
accepted: 15 04 2019
entrez: 4 5 2019
pubmed: 3 5 2019
medline: 31 12 2019
Statut: epublish

Résumé

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. We use PCR and sequencing analysis to characterize pericentromeric K111 proviruses in DNA from individuals of diverse ethnicities and patients with different diseases. 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]. 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.

Sections du résumé

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.

Identifiants

DOI: 10.1186/s12920-019-0505-8 PMID: 31046767 PMC: PMC6498702
pubmed: 31046767
doi: 10.1186/s12920-019-0505-8
pii: 10.1186/s12920-019-0505-8
pmc: PMC6498702
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

58

Subventions

Organisme : NIAID NIH HHS
ID : U01 AI035042
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG009784
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI110259
Pays : United States
Organisme : FIC NIH HHS
ID : D43 TW009106
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001079
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA134274
Pays : United States
Organisme : NCI NIH HHS
ID : K22 CA177824
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI035041
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI035043
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146201
Pays : United States
Organisme : BLRD VA
ID : I01 BX002358
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI035040
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI035039
Pays : United States

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Auteurs

Mark H Kaplan (MH)

Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.

Mark Kaminski (M)

Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.

Judith M Estes (JM)

Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.

Scott D Gitlin (SD)

Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
Ann Arbor Veterans Affairs Hospital, Ann Arbor, MI, 48105, USA.

Joseph Zahn (J)

Division of Dermatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.

James T Elder (JT)

Division of Dermatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
Ann Arbor Veterans Affairs Hospital, Ann Arbor, MI, 48105, USA.

Trilokraj Tejasvi (T)

Division of Dermatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
Ann Arbor Veterans Affairs Hospital, Ann Arbor, MI, 48105, USA.

Elizabeth Gensterblum (E)

Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.

Amr H Sawalha (AH)

Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.

Joseph Patrick McGowan (JP)

Division of Infectious Diseases, The Feinstein Institute for Medical research, Manhasset, NY, 11030, USA.

Michael H Dosik (MH)

Hematology Oncology Associates, Setauket, NY, 11776, USA.

Haner Direskeneli (H)

Division of Rheumatology, School of Medicine, Marmara University, Istanbul, Turkey.

Guher Saruhan Direskeneli (GS)

Department of Physiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Sally N Adebamowo (SN)

Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.

Clement A Adebamowo (CA)

Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.

Mohammad Sajadi (M)

Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.

Rafael Contreras-Galindo (R)

Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA. rafaelc@med.umich.edu.
Hormel Institute, University of Minnesota, Austin, MN, 55912, USA. rafaelc@med.umich.edu.

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Recherchemedicale.com › Phénomènes génétiques › Structures génétiques › Structures de chromosome › Centromère › Structural variation of centromeric endogenous...
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Recherchemedicale.com › Maladies du système immunitaire › Syndromes immunoprolifératifs › Syndromes lymphoprolifératifs › Lymphomes › Lymphome malin non hodgkinien › Lymphome T › Lymphome T cutané › Structural variation of centromeric endogenous...
Recherchemedicale.com › Maladies du système immunitaire › Syndromes immunoprolifératifs › Syndromes lymphoprolifératifs › Syndrome de Sézary › Structural variation of centromeric endogenous...