Naf1 regulates HIV-1 latency by suppressing viral promoter-driven gene expression in primary CD4+ T cells

Chuan Li, Hai Bo Wang, Wen Dong Kuang, Xiao Xin Ren, Shu Ting Song, Huan Zhang Zhu, Qiang Li, Li Ran Xu, Hui Jun Guo, Li Wu, Jian Hua Wang

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

HIV-1 latency is characterized by reversible silencing of viral transcription driven by the long terminal repeat (LTR) promoter of HIV-1. Cellular and viral factors regulating LTR activity contribute to HIV-1 latency, and certain repressive cellular factors modulate viral transcription silencing. Nef-associated factor 1 (Naf1) is a host nucleocytoplasmic shuttling protein that regulates multiple cellular signaling pathways and HIV-1 production. We recently reported that nuclear Naf1 promoted nuclear export of unspliced HIV-1 gag mRNA, leading to increased Gag production. Here we demonstrate new functions of Naf1 in regulating HIV-1 persistence. We found that Naf1 contributes to the maintenance of HIV-1 latency by inhibiting LTRdriven HIV-1 gene transcription in a nuclear factor kappa B-dependent manner. Interestingly, Naf1 knockdown significantly enhanced viral reactivation in both latently HIV-1-infected Jurkat T cells and primary central memory CD4+ T cells. Furthermore, Naf1 knockdown in resting CD4+ T cells from HIV-1-infected individuals treated with antiretroviral therapy significantly increased viral reactivation upon T-cell activation, suggesting an important role of Naf1 in modulating HIV-1 latency in vivo. Our findings provide new insights for a better understanding of HIV-1 latency and suggest that inhibition of Naf1 activity to activate latently HIV-1-infected cells may be a potential therapeutic strategy.

Original languageEnglish (US)
Article numbere01830-16
JournalJournal of virology
Volume91
Issue number1
DOIs
StatePublished - 2017
Externally publishedYes

Keywords

  • HIV-1 latency
  • HIV-1 Nef-associated factor 1
  • NF-κB
  • Transcription

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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