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Journal of virology
Aug, 2012;86 (15): 7790-805.

Expression of human endogenous retrovirus type K (HML-2) is activated by the Tat protein of HIV-1.

Marta J Gonzalez-Hernandez, Michael D Swanson, Rafael Contreras-Galindo, Sarah Cookinham, Steven R King, Richard J Noel, Mark H Kaplan, David M Markovitz
Author Information
  1. Marta J Gonzalez-Hernandez: Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
PMID: 22593154 DOI: 10.1128/JVI.07215-11

Abstract

Human endogenous retroviruses (HERVs) make up 8% of the human genome. The expression of HERV-K (HML-2), the family of HERVs that most recently entered the genome, is tightly regulated but becomes markedly increased after infection with HIV-1. To better understand the mechanisms involved in this activation, we explored the role of the HIV-1 Tat protein in inducing the expression of these endogenous retroviral genes. Administration of recombinant HIV-1 Tat protein caused a 13-fold increase in HERV-K (HML-2) gag RNA transcripts in Jurkat T cells and a 10-fold increase in primary lymphocytes, and the expression of the HERV-K (HML-2) rec and np9 oncogenes was also markedly increased. This activation was seen especially in lymphocytes and monocytic cells, the natural hosts for HIV-1 infection. Luciferase reporter gene assays demonstrated that the effect of Tat on HERV-K (HML-2) expression occurred at the level of the transcriptional promoter. The transcription factors NF-κB and NF-AT contribute to the Tat-induced activation of the promoter, as shown by chromatin immunoprecipitation assays, mutational analysis of the HERV-K (HML-2) long terminal repeat, and treatments with agents that inhibit NF-κB or NF-AT activation. These studies demonstrate that HIV-1 Tat plays an important role in activating expression of HERV-K (HML-2) in the setting of HIV-1 infection.

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Grants

  1. R01 AI062248/NIAID NIH HHS
  2. 1F31CA150523-01/NCI NIH HHS
  3. F31 CA150523/NCI NIH HHS
  4. G12 MD007579/NIMHD NIH HHS
  5. R01CA144043/NCI NIH HHS
  6. R01AI062248/NIAID NIH HHS
  7. R01 CA144043/NCI NIH HHS
  8. G12 RR003050/NCRR NIH HHS

MeSH Term

Endogenous Retroviruses
Gene Expression Regulation, Viral
Gene Products, env
HIV Infections
HIV-1
Humans
Jurkat Cells
Recombinant Proteins
Viral Envelope Proteins
Virus Activation
tat Gene Products, Human Immunodeficiency Virus

Chemicals

ERVK-6 protein, human endogenous retrovirus
Gene Products, env
Np9 protein, HERV-K, human
Recombinant Proteins
Viral Envelope Proteins
tat Gene Products, Human Immunodeficiency Virus
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.
Article has an altmetric score of 4

Word Cloud

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