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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Antagonistic role of IL-1 beta and NLRP3/IL-18 genetics in chronic HIV-1 infection

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Author(s):
Reis, Edione C. [1] ; Leal, Vinicius N. C. [1] ; da Silva, Lais T. [2] ; dos Reis, Marilia M. L. [3] ; Arganaraz, Enrique R. [3] ; Oshiro, Telma M. [2] ; Pontillo, Alessandra [1]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, Lab Imunogenet, Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Lab Invest Dermatol & Imunodeficiencias LIM 56, Sao Paulo, SP - Brazil
[3] Univ Brasilia UNB, Fac Ciencias Saude, Lab Virol Mol, Brasilia, DF - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Clinical Immunology; v. 209, DEC 2019.
Web of Science Citations: 1
Abstract

Host genetics affects both susceptibility and progression of HIV-1 infection. NLRP3 inflammasome provides a first-line defense in viral infections, and, accordingly, gain-of-function variants in NLRP3 have been associated with protection against HIV-1. Despite antiretroviral treatment (ART), HIV-infected patients continue to present systemic inflammation with a heterogeneous prognosis. As NLRP3 inflammasome is involved in several chronic diseases by amplifying ``sterile{''} inflammation, its role in chronic phase of HIV infection has been postulated. Little is known about inflammasome genetics in HIV-infected patients and whether it may play a role in the different clinical outcomes. Therefore, we questioned whether NLRP3 inflammasome genetics could affect the clinical course of HIV-1 infection as it does in host/virus interaction. For this purpose, we analyzed selected single nucleotide polymorphisms (SNPs) in ART-treated HIV-infected patients (n = 300), in Long Term Non-Progressors/Elite Controllers and progressors (n = 133), and in HIV-infected individuals submitted to dendritic cell (DC)-based immunotherapy (n = 19). SNPs leading to increased activation of NLRP3 inflammasome are beneficial for patients, while SNPs that negatively affect NLRP3 activation or IL-18 production, detrimental. In contrast, gain-of-function variant in IL1B is also detrimental for patients, suggesting that while IL-1 beta possible contributes to immune exhaustion, the axis NLRP3-inflammasome/IL-18 could act positively in chronic infection. Functional assays supported genetic results: NLRP3 variants associated with good quality HIV + DC, and ILIB -511C > T with a poor one. Loss-of-function SNPs affect HIV + T cells proliferation. These findings proposed for the first time that NLRP3 inflammasome, mainly through IL-18, play a protective role in chronic HIV infection. (AU)

FAPESP's process: 15/23395-6 - Immunogenetics of the inflammasome and translational study "from bed to bench and back": analysis of variations in inflammasome genes in monogenic and multifactorial autoinflammatory diseases for differential diagnosis and therapeutic applications
Grantee:Alessandra Pontillo
Support Opportunities: Regular Research Grants
FAPESP's process: 13/06142-1 - Genomic signature of immune response against HIV-1 and its implications for dendritic cell-based therapeutic vaccine against HIV-1
Grantee:Alessandra Pontillo
Support Opportunities: Regular Research Grants
FAPESP's process: 15/50650-7 - Characterization of novel molecular players in the control of obesity and obesity-induced inflammation
Grantee:Alessandra Pontillo
Support Opportunities: Regular Research Grants