RIG-I detects HIV-1 infection and mediates type i interferon response in human macrophages from patients with HIV-1-associated neurocognitive disorders

M. Q. Wang, Y. L. Huang, J. Huang, J. L. Zheng, G. X. Qian

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The aim of this study was to explore the precise role of retinoic acid-inducible gene-I (RIG-I) signaling in human immunodeficiency virus type 1 (HIV-1)-infected macrophages from patients with HIV-1-associated neurocognitive disorders (HAND). Postmortem brain tissues were collected from patients with HIV-1-associated dementia and were compared to samples collected from HIV serum-positive patients without dementia and HIV serum-negative patients. A human monocyte-derived macrophage (MDM) primary culture system was established to evaluate the expression of RIG-I in these samples. Knockdown of RIG-I pathways genes was employed and STAT1 expression and phosphorylation levels were examined to explore the molecular mechanisms of HAND. The expression of RIG-I in postmortem brain tissue from HAND patients was significantly higher than in patients who were HIV serum-positive without dementia or HIV serum-negative. Moreover, we demonstrated that HIV-1 infection could result in a significant increase in the level of RIG-I in human MDMs. Moreover, a correlation was found between the increase in RIG-I expression and STAT1 expression and phosphorylation. Accordingly, knockdown of RIG-I decreased the phosphorylation of STAT1 and downregulated interferon-related genes. These observations highlight the importance of RIG-I signaling in anti-HIV innate immunity in macrophages, which may be beneficial for the treatment of HIV and aid in the understanding of the neuropathogenesis of HAND.

Original languageEnglish (US)
Pages (from-to)13799-13811
Number of pages13
JournalGenetics and Molecular Research
Volume14
Issue number4
DOIs
StatePublished - Oct 28 2015

Keywords

  • HIV-1 associated neurocognitive disorders
  • Human immunodeficiency virus type I
  • Monocyte-derived macrophage
  • Retinoic acid-inducible gene-I

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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