The Role of Inflammasome Activation in Early HIV Infection.

Cyril Jabea Ekabe,Njinju Asaba Clinton,Jules Kehbila,Ngangom Chouamo Franck,Ran Wang

doi:10.1155/2021/1487287

Cyril Jabea Ekabe, Njinju Asaba Clinton + Show 3 more

Open Access

https://doi.org/10.1155/2021/1487287

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Abstract

The inflammasome pathway is an important arm of the innate immune system that provides antiviral immunity against many viruses. The main pathways involved in virus infections include the NLRP3, IFI16, and AIM2 pathways. However, a succinct understanding of its role in HIV is not yet well elucidated. In this review, we showed that NLRP3 inflammasome activation plays a vital role in inhibiting HIV entry into target cells via the purinergic pathway; IFI16 detects intracellular HIV ssDNA, triggers interferon I and III production, and inhibits HIV transcription; and AIM2 binds to HIV dsDNA and triggers acute inflammation and pyroptosis. Remarkably, by understanding these mechanisms, new therapeutic strategies can be developed against the disease.

Highlights

HIV infection is a global pandemic affecting about 38 million people worldwide, with approximately two-thirds of the patients found in Africa [1]
Upon entry of the nucleocapsid into the cytoplasm, the virus undergoes partial uncoating exposing the viral genome and proteins to cytoplasmic sensors like DNA sensors, RNA sensors, endosomal TLRs (Toll-like receptors), and NLRs receptors which can trigger the elimination of the virus
Reports have shown that the activation of the interferon-gammainducible protein 16 (IFI16) inflammasome during an abortive HIV infection is linked to the depletion of CD4+ T cells through the process of pyroptosis mediated by activated caspase 1 [39]

Summary

Introduction

HIV infection is a global pandemic affecting about 38 million people worldwide, with approximately two-thirds of the patients found in Africa [1]. The HIV virus is an enveloped positive single-strand RNA (ssRNA) retrovirus that primarily infects CD4 T cells, as well as macrophages, and perhaps dendritic cells. It interacts with the CD4 receptors, and coreceptors (CXCR4, CCR5) expressed in these cells [2]. Inflammasomes are generally categorized into two: proinflammatory inflammasomes (NLRP3 and NLRC4) and anti-inflammatory inflammasomes (NLRP12, NLRX1, NLRC3, and NLRC5) [7,8,9] These inflammasomes can either contain the PYD domain (NLRP3, NLRP1, AIM2, IFI16, and pyrin) or CARD domain (NLRC4, NLRC5) or the BIR domain (NAIP). This review is aimed at discussing the main inflammasome pathways important in HIV infection, and whether they can be harnessed as therapeutic strategies for the disease

NLRP3 Activation in HIV Infection

IFI16 Activation in HIV Infection

AIM2 Activation in HIV Infection

Conclusion and Future Perspective

Findings

Conflicts of Interest