Disruption of polycomb repressor complex-mediated gene silencing reactivates HIV-1 provirus in latently infected Cells

Cheol Hee Yoon, Dai Ho Jang, Kyung Chang Kim, Soon Young Park, Hye Young Kim, Sung Soon Kim, Sung-Gil Chi, Byeong Sun Choi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objectives: Persistent HIV-1 infections are characterized by a long silent infection period in resting CD4+ T cells, which allows them to escape the host immune response. Several HIV-1 latency mechanisms have been reported, but the molecular mechanism underlying polycomb repressor complex (PRC)-mediated HIV-1 latency remains poorly understood. Methods: Expression of PRC proteins in latent cells was measured by Western blot. Knockdowns of PRC genes were conducted by the specific siRNA and methylations at H3K27 on the proviral LTR were investigated by ChIP assay. Results: PRC proteins (EED, BMI-1, and RNF2) were dramatically downregulated in latent cells after PMA treatment. The downregulation of PRC proteins was followed by a decrease in the methylation of H3K27 and ubiquitination of H2AK119 in the PMA-treated latent cells. siRNA knockdowns of EED and BMI-1 also enhanced HIV-1 reactivation significantly in latently infected cells. By contrast, proteasomal inhibitor MG132 successfully abrogated the PMA-induced downregulation of PRCs. In particular, di-/tri-methylations of histone-3 in the proviral LTR was absent from latent cells after PMA treatment. Conclusions: This study shows that PRC is strongly related to the control of HIV-1 latency and that PRC-breaking agents may be helpful for purging HIV-1 from latent reservoirs.

Original languageEnglish
Pages (from-to)116-120
Number of pages5
JournalIntervirology
Volume57
Issue number2
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

Proviruses
Gene Silencing
HIV-1
Repressor Proteins
Methylation
Down-Regulation
Small Interfering RNA
Ubiquitination
Histones
HIV Infections
Western Blotting
T-Lymphocytes
Infection
Genes

Keywords

  • HIV-1 latency
  • HIV-1 reactivation
  • Methylations of H3K27
  • Polycomb repressor complex
  • Proteasomal inhibitor MG132

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Yoon, C. H., Jang, D. H., Kim, K. C., Park, S. Y., Kim, H. Y., Kim, S. S., ... Choi, B. S. (2014). Disruption of polycomb repressor complex-mediated gene silencing reactivates HIV-1 provirus in latently infected Cells. Intervirology, 57(2), 116-120. https://doi.org/10.1159/000360224

Disruption of polycomb repressor complex-mediated gene silencing reactivates HIV-1 provirus in latently infected Cells. / Yoon, Cheol Hee; Jang, Dai Ho; Kim, Kyung Chang; Park, Soon Young; Kim, Hye Young; Kim, Sung Soon; Chi, Sung-Gil; Choi, Byeong Sun.

In: Intervirology, Vol. 57, No. 2, 01.01.2014, p. 116-120.

Research output: Contribution to journalArticle

Yoon, Cheol Hee ; Jang, Dai Ho ; Kim, Kyung Chang ; Park, Soon Young ; Kim, Hye Young ; Kim, Sung Soon ; Chi, Sung-Gil ; Choi, Byeong Sun. / Disruption of polycomb repressor complex-mediated gene silencing reactivates HIV-1 provirus in latently infected Cells. In: Intervirology. 2014 ; Vol. 57, No. 2. pp. 116-120.
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