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

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7790-7804
Number of pages15
JournalJournal of virology
Volume86
Issue number15
DOIs
StatePublished - 2012
Externally publishedYes

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