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

• Published in: Memórias do Instituto Oswaldo Cruz Vol. 119; p. e240071
• Main Authors: de Azevedo, Suwellen Sardinha Dias, Ribeiro-Alves, Marcelo, Côrtes, Fernanda Heloise, Delatorre, Edson, Hoagland, Brenda, Villela, Larissa M, Grinsztejn, Beatriz, Veloso, Valdilea Gonçalvez, Morgado, Mariza G, Souza, Thiago Moreno L, Bello, Gonzalo
• Format: Journal Article
• Language: English
• Published: Brazil Instituto Oswaldo Cruz, Ministério da Saúde 01.01.2024
• Subjects: Adult; Case-Control Studies; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Endogenous Retroviruses - genetics; Endogenous Retroviruses - immunology; Female; HIV Infections - genetics; HIV Infections - immunology; HIV Infections - virology; HIV-1 - genetics; HIV-1 - immunology; Humans; Immunity, Innate - genetics; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Male; Middle Aged; PARASITOLOGY; Ribonucleases - genetics; Ribonucleases - metabolism; RNA, Viral - genetics; Transcription Factors - genetics; TROPICAL MEDICINE; Virus Replication - genetics; HIV-1; ERVK-6; elite controllers; viremic controllers; restriction factors
• ISSN: 0074-0276; 1678-8060; 1678-8060
• DOI: 10.1590/0074-02760240071

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. To understand the ability of HICs to control the expression of endogenous retroviruses. 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. 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. 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.