title: Expression of human endogenous retrovirus type K (HML-2) is activated by the Tat protein of HIV-1.
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.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Marta J
authors.initials: MJ
authors.lastname: Gonzalez-Hernandez
authors.forename: Michael D
authors.initials: MD
authors.lastname: Swanson
authors.forename: Rafael
authors.initials: R
authors.lastname: Contreras-Galindo
authors.forename: Sarah
authors.initials: S
authors.lastname: Cookinham
authors.forename: Steven R
authors.initials: SR
authors.lastname: King
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Noel
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
authors.forename: David M
authors.initials: DM
authors.lastname: Markovitz
mesh_terms: D020077:Endogenous Retroviruses / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D015686:Gene Products, env / Q000096:biosynthesis* / Q000235:genetics; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000096:biosynthesis* / Q000235:genetics; D014775:Virus Activation; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: C485839:ERVK-6 protein, human endogenous retrovirus; D015686:Gene Products, env; C469430:Np9 protein, HERV-K, human; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus