HIV-1 controllers exhibit an enhanced antiretroviral innate state characterised by overexpression of p21 and MCPIP1 and silencing of ERVK-6 RNA expression.

Autor:	de Azevedo SSD; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de AIDS & Imunologia Molecular, Rio de Janeiro, RJ, Brasil., Ribeiro-Alves M; Fundação Oswaldo Cruz-Fiocruz, Instituto Nacional de Infectologia Evandro Chagas, Laboratório de Pesquisa Clínica em DST/AIDS, Rio de Janeiro, RJ, Brasil., Côrtes FH; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de AIDS & Imunologia Molecular, Rio de Janeiro, RJ, Brasil., Delatorre E; Universidade Federal do Espírito Santo, Centro de Ciências da Saúde, Departamento de Patologia, Laboratório de Genômica e Ecologia Viral, Vitória, ES, Brasil., Hoagland B; Fundação Oswaldo Cruz-Fiocruz, Instituto Nacional de Infectologia Evandro Chagas, Laboratório de Pesquisa Clínica em DST/AIDS, Rio de Janeiro, RJ, Brasil., Villela LM; Fundação Oswaldo Cruz-Fiocruz, Instituto Nacional de Infectologia Evandro Chagas, Laboratório de Pesquisa Clínica em DST/AIDS, Rio de Janeiro, RJ, Brasil., Grinsztejn B; Fundação Oswaldo Cruz-Fiocruz, Instituto Nacional de Infectologia Evandro Chagas, Laboratório de Pesquisa Clínica em DST/AIDS, Rio de Janeiro, RJ, Brasil., Veloso VG; Fundação Oswaldo Cruz-Fiocruz, Instituto Nacional de Infectologia Evandro Chagas, Laboratório de Pesquisa Clínica em DST/AIDS, Rio de Janeiro, RJ, Brasil., Morgado MG; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de AIDS & Imunologia Molecular, Rio de Janeiro, RJ, Brasil., Souza TML; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Imunofarmacologia, Rio de Janeiro, RJ, Brasil.; Fundação Oswaldo Cruz-Fiocruz, Instituto Nacional de Ciência e Tecnologia de Inovação em Doenças de Populações Negligenciadas, Rio de Janeiro, RJ, Brasil., Bello G; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de AIDS & Imunologia Molecular, Rio de Janeiro, RJ, Brasil.; Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Arbovírus e Vírus Hemorrágicos, Rio de Janeiro, RJ, Brasil.
Jazyk:	angličtina
Zdroj:	Memorias do Instituto Oswaldo Cruz [Mem Inst Oswaldo Cruz] 2024 Sep 16; Vol. 119, pp. e240071. Date of Electronic Publication: 2024 Sep 16 (Print Publication: 2024).
DOI:	10.1590/0074-02760240071
Abstrakt:	Background: Human immunodeficiency virus (HIV)-1 infection can activate the expression of human endogenous retroviruses (HERVs), particularly HERV-K (HML-2). HIV controllers (HICs) are rare people living with HIV (PLWHs) who naturally control HIV-1 replication and overexpress some cellular restriction factors that negatively regulate the LTR-driven transcription of HIV-1 proviruses. Objectives: To understand the ability of HICs to control the expression of endogenous retroviruses. Methods: We measured endogenous retrovirus type K6 (ERVK-6) RNA expression in peripheral blood mononuclear cells (PBMCs) of HICs (n = 23), antiretroviral (ART)-suppressed subjects (n = 8), and HIV-1-negative (NEG) individuals (n = 10) and correlated the transcript expression of ERVK-6 with multiple HIV-1 cellular restriction factors. Findings: Our study revealed that ERVK-6 RNA expression in PBMCs from HICs was significantly downregulated compared with that in both the ART and NEG control groups. Moreover, we detected that ERVK-6 RNA levels in PBMCs across all groups were negatively correlated with the expression levels of p21 and MCPIP1, two cellular restriction factors that limit the activation of macrophages and T cells by downregulating the activity of NF-kB. Main Conclusions: These findings support the hypothesis that HICs activate innate antiviral mechanisms that may simultaneously downregulate the transcription of both exogenous (HIV-1) and endogenous (ERVK-6) retroviruses. Future studies with larger cohorts should be performed to confirm this hypothesis and to explore the role of p21 and MCPIP1 in regulating HERV-K expression in physiological and pathological conditions.
Databáze:	MEDLINE
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