Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

HIV-1 Controllers Exhibit an Enhanced Antiretroviral Innate State Characterized by Overexpression of p21 and MCPIP1 and Silencing of Endogenous Retroviruses

Suwellen Sardinha Dias de Azevedo
,
Marcelo Ribeiro Alves
,
Fernanda Heloise Côrtes
,
Edson Delatorre
,
Brenda Hoagland
,
Larissa M. Villela
,
Beatriz Grinsztejn
,
Valdiléa Gonçalves Veloso
,
Mariza Gonçalves Morgado
ORCID logo ,
Thiago Moreno Souza
,
Gonzalo Bello
*
Version 1 : Received: 25 September 2023 / Approved: 26 September 2023 / Online: 27 September 2023 (05:09:21 CEST)

How to cite: Azevedo, S.S.D.D.; Ribeiro Alves, M.; Côrtes, F.H.; Delatorre, E.; Hoagland, B.; Villela, L.M.; Grinsztejn, B.; Veloso, V.G.; Morgado, M.G.; Souza, T.M.; Bello, G. HIV-1 Controllers Exhibit an Enhanced Antiretroviral Innate State Characterized by Overexpression of p21 and MCPIP1 and Silencing of Endogenous Retroviruses. Preprints 2023, 2023091808. https://doi.org/10.20944/preprints202309.1808.v1 Azevedo, S.S.D.D.; Ribeiro Alves, M.; Côrtes, F.H.; Delatorre, E.; Hoagland, B.; Villela, L.M.; Grinsztejn, B.; Veloso, V.G.; Morgado, M.G.; Souza, T.M.; Bello, G. HIV-1 Controllers Exhibit an Enhanced Antiretroviral Innate State Characterized by Overexpression of p21 and MCPIP1 and Silencing of Endogenous Retroviruses. Preprints 2023, 2023091808. https://doi.org/10.20944/preprints202309.1808.v1

Abstract

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 (PLWH) who naturally control HIV-1 replication. The ability of HICs to control the expression of endogenous retroviruses has not been previously addressed. In this study, we measured ERVK-6 RNA expression in 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 restriction factors. Our study reveals that ERVK-6 RNA expression in PBMCs from HICs was significantly downregulated compared with both 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. In our previous study, these two cellular restriction factors were upregulated in HICs compared with control groups. Interestingly, p21 and MCPIP1 limit the activation of macrophages and T cells by downregulating the activity of NF-kB, a transcription factor that stimulates the LTR-driven transcription of HIV-1 and HERV-K proviruses. These findings support that HICs activate innate antiviral mechanisms that may simultaneously downregulate the transcription of both HIV-1 and endogenous retroviruses.

Keywords

HIV-1; HERV-K; elite controllers; viremic controllers; restriction factors

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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