PMID:22593154

Citation	Gonzalez-Hernandez, MJ, Swanson, MD, Contreras-Galindo, R, Cookinham, S, King, SR, Noel, RJ Jr, Kaplan, MH and Markovitz, DM (2012) Expression of human endogenous retrovirus type K (HML-2) is activated by the Tat protein of HIV-1. J. Virol. 86:7790-805
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.
Links	PubMed PMC3421662 Online version:10.1128/JVI.07215-11
Keywords	Endogenous Retroviruses/physiology; Gene Expression Regulation, Viral; Gene Products, env/biosynthesis; Gene Products, env/genetics; HIV Infections/genetics; HIV Infections/metabolism; HIV-1/genetics; HIV-1/metabolism; Humans; Jurkat Cells; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Recombinant Proteins/pharmacology; Viral Envelope Proteins/biosynthesis; Viral Envelope Proteins/genetics; Virus Activation; tat Gene Products, Human Immunodeficiency Virus/genetics; tat Gene Products, Human Immunodeficiency Virus/metabolism; tat Gene Products, Human Immunodeficiency Virus/pharmacology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HV1BR:TAT	involved_in	GO:0052312: modulation of transcription in other organism involved in symbiotic interaction	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HV1BR:TAT		GO:0052312: modulation of transcription in other organism involved in symbiotic interaction	ECO:0000314:		P		Figure 3A demonstrates that the Tat addition to Jurkat T cells caused a 10.8-fold increase in Human Endogenous Retrovirus Type-K (HML-2) gag RNA production after 6 hours. This concludes that the tat protein activates the expression of HML-2.	complete CACAO 6527

References

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