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HIV-1 infection induces interleukin-1β production via TLR8 protein-dependent and NLRP3 inflammasome mechanisms in human monocytes.

Authors
  • Guo, Haitao
  • Gao, Jianmei
  • Taxman, Debra J
  • Ting, Jenny P Y
  • Su, Lishan
Type
Published Article
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry and Molecular Biology
Publication Date
Aug 01, 2014
Volume
289
Issue
31
Pages
21716–21726
Identifiers
DOI: 10.1074/jbc.M114.566620
PMID: 24939850
Source
Medline
Keywords
License
Unknown

Abstract

The induction of inflammatory cytokines such as IL-1β is associated with the progression of human immunodeficiency virus, type 1 (HIV-1) disease or AIDS. Unlike most inflammatory cytokines that are regulated by NF-κB at the transcriptional level, production of mature IL-1β also depends on inflammasome activation. The mechanism by which HIV-1 induces pro-IL-1β expression and activates inflammasomes to cleave pro-IL-1β into its bioactive form is not clearly defined. We report here that HIV-1 infection in human monocytes efficiently induced IL-1β expression and inflammasome activation. Toll-like receptor 8 (TLR8) was required for inducing pro-IL-1β expression, whereas the NLRP3 inflammasome was required for IL-1β maturation and release. Furthermore, the lysosomal protease cathepsin B and HIV-1 induced production of reactive oxygen species were critical for HIV-induced inflammasome activation and IL-1β production. HIV-1 entry, reverse transcription, and integration were all required for both pro-IL-1β expression and inflammasome activation. Finally, we show that HIV-1-derived RNA was sufficient to induce both pro-IL-1β expression and inflammasome activation. We conclude that HIV-1 infection induced the expression of pro-IL-1β via TLR8-mediated mechanisms and activated caspase-1 through the NLRP3 inflammasome to cleave pro-IL-1β into bioactive IL-1β. These findings help to elucidate mechanisms of HIV-1 disease progression and identify novel targets for treating HIV-1 induced inflammation and immune activation.

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