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Regulation of the human endogenous retrovirus K (HML-2) transcriptome by the HIV-1 Tat protein.

AbstractUNLABELLED:
Approximately 8% of the human genome is made up of endogenous retroviral sequences. As the HIV-1 Tat protein activates the overall expression of the human endogenous retrovirus type K (HERV-K) (HML-2), we used next-generation sequencing to determine which of the 91 currently annotated HERV-K (HML-2) proviruses are regulated by Tat. Transcriptome sequencing of total RNA isolated from Tat- and vehicle-treated peripheral blood lymphocytes from a healthy donor showed that Tat significantly activates expression of 26 unique HERV-K (HML-2) proviruses, silences 12, and does not significantly alter the expression of the remaining proviruses. Quantitative reverse transcription-PCR validation of the sequencing data was performed on Tat-treated PBLs of seven donors using provirus-specific primers and corroborated the results with a substantial degree of quantitative similarity.
IMPORTANCE:
The expression of HERV-K (HML-2) is tightly regulated but becomes markedly increased following infection with HIV-1, in part due to the HIV-1 Tat protein. The findings reported here demonstrate the complexity of the genome-wide regulation of HERV-K (HML-2) expression by Tat. This work also demonstrates that although HERV-K (HML-2) proviruses in the human genome are highly similar in terms of DNA sequence, modulation of the expression of specific proviruses in a given biological situation can be ascertained using next-generation sequencing and bioinformatics analysis.
AuthorsMarta J Gonzalez-Hernandez, James D Cavalcoli, Maureen A Sartor, Rafael Contreras-Galindo, Fan Meng, Manhong Dai, Derek Dube, Anjan K Saha, Scott D Gitlin, Gilbert S Omenn, Mark H Kaplan, David M Markovitz
JournalJournal of virology (J Virol) Vol. 88 Issue 16 Pg. 8924-35 (Aug 2014) ISSN: 1098-5514 [Electronic] United States
PMID24872592 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014, American Society for Microbiology. All Rights Reserved.
Chemical References
  • Gene Products, tat
  • RNA, Viral
  • Viral Proteins
Topics
  • Cells, Cultured
  • Endogenous Retroviruses (genetics, metabolism)
  • Gene Products, tat (genetics, metabolism)
  • Genome, Human (genetics)
  • HIV Infections (genetics, metabolism)
  • HIV-1 (genetics, metabolism)
  • High-Throughput Nucleotide Sequencing (methods)
  • Humans
  • Lymphocytes (virology)
  • Proviruses (genetics, metabolism)
  • RNA, Viral (genetics)
  • Transcriptome (genetics)
  • Viral Proteins (genetics, metabolism)

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