Sterol metabolism modulates susceptibility to HIV-1 Infection

Irma Saulle, Salomè Valentina Ibba, Cecilia Vittori, Claudio Fenizia, Vincenzo Mercurio, Francesca Vichi, Sergio Lo Caputo, Daria Trabattoni, Mario Clerici, Mara Biasin

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: 25-hydroxylase (CH25H) is an interferon-stimulated gene (ISG), which catalyzes the synthesis of 25-hydroxycholesterol (25HC). 25HC intervenes in metabolic and infectious processes and controls cholesterol homeostasis and influences viral entry into host cells. We verified whether natural resistance to HIV-1 infection in HIV-1-exposed seronegative (HESN) individuals is at least partially mediated by particularities in sterol biosynthesis. METHODS: Peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages (MDMs) isolated from 15 sexually exposed HESN and 15 healthy controls were in vitro HIV-1-infected and analyzed for: percentage of IFNα-producing plasmacytoid dendritic cells (pDCs); cholesterol signaling and inflammatory response RNA expression; resistance to HIV-1 infection. MDMs from five healthy controls were in vitro HIV-1-infected in the absence/presence of exogenously added 25HC. RESULTS: IFNα-producing pDCs were augmented in HESN compared with healthy controls both in unstimulated and in in vitro HIV-1-infected PBMCs (P < 0.001). An increased expression of CH25H and of a number of genes involved in cholesterol metabolism (ABCA1, ABCG1, CYP7B1, LXRα, OSBP, PPARγ, SCARB1) was observed as well; this, was associated with a reduced susceptibility to in-vitro HIV-1-infection of PBMCs and MDMs (P < 0.01). Notably, addition of 25HC to MDMs resulted in increased cholesterol efflux and augmented resistance to in-vitro HIV-1-infection. CONCLUSION: Results herein show that in HESN sterol metabolism might be particularly efficient. This could be related to the activation of the IFNα pathway and results into a reduced susceptibility to in-vitro HIV-1 infection. These results suggest a possible basis for therapeutic interventions to modulate HIV-1 infection.

Original languageEnglish
Pages (from-to)1593-1602
Number of pages10
JournalAIDS (London, England)
Volume34
Issue number11
DOIs
Publication statusPublished - Sep 1 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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