Abortive HIV-1 RNA Induces Pro-IL-1β Maturation Via Protein Kinase PKR and Inflammasome Activation in Humans

Overview

Journal Eur J Immunol

Specialty Allergy & Immunology

Date 2021 Jul 5

PMID 34223639

Citations 9

Authors

Melissa Stunnenberg

John L van Hamme

Marjolein Trimp

Sonja I Gringhuis

Teunis B H Geijtenbeek

Affiliations

Soon will be listed here.

Abstract

The proinflammatory cytokine IL-1β mediates high levels of immune activation observed during acute and chronic human immunodeficiency virus 1 (HIV-1) infection. Little is known about the mechanisms that drive IL-1β activation during HIV-1 infection. Here, we have identified a crucial role for abortive HIV-1 RNAs in inducing IL-1β in humans. Abortive HIV-1 RNAs were sensed by protein kinase RNA-activated (PKR), which triggered activation of the canonical NLRP3 inflammasome and caspase-1, leading to pro-IL-1β processing and secretion. PKR activated the inflammasome via ROS generation and MAP kinases ERK1/2, JNK, and p38. Inhibition of PKR during HIV-1 infection blocked IL-1β production. As abortive HIV-1 RNAs are produced during productive infection and latency, our data strongly suggest that targeting PKR signaling might attenuate immune activation during acute and chronic HIV-1 infection.

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