Targeting Epigenetics to Cure HIV-1: Lessons From (and for) Cancer Treatment.

J Peter Svensson

doi:10.3389/fcimb.2021.668637

Abstract

The Human Immunodeficiency Virus type 1 (HIV-1) integrates in the host genome as a provirus resulting in a long-lived reservoir of infected CD4 cells. As a provirus, HIV-1 has several aspects in common with an oncogene. Both the HIV-1 provirus and oncogenes only cause disease when expressed. A successful cure of both cancer and HIV-1 includes elimination of all cells with potential to regenerate the disease. For over two decades, epigenetic drugs developed against cancer have been used in the HIV-1 field to modulate the state of the proviral chromatin. Cells with an intact HIV-1 provirus exist in three states of infection: productive, inducible latent, and non-inducible latent. Here focus is on HIV-1, transcription control and chromatin structure; how the inducible proviruses are maintained in a chromatin structure that allows reactivation of transcription; and how transcription switches between different stages to allow for an abundance of different transcripts from a single promoter. Recently it was shown that a functional cure of HIV can be achieved by encapsulating all intact HIV-1 proviruses in heterochromatin, giving hope that epigenetic interventions may be used to end the HIV-1 epidemic.

Highlights

Human Immunodeficiency Virus type 1 (HIV-1) infection increases a person’s risk of acquiring certain types of cancer (Hernández-Ramıŕ ez et al, 2017)
Because the HIV-1 virus targets active cells and integration occurs in active chromatin regions, conditions are beneficial for immediate viral production
Even though the provirus is predominantly integrated in open regions, in time the provirus takes on a compact structure, and heterochromatin defining histone modifications appear on the proviral chromatin (Lindqvist et al, 2020)

Summary

Introduction

HIV-1 infection increases a person’s risk of acquiring certain types of cancer (Hernández-Ramıŕ ez et al, 2017). The complexity of the HIV-1 reservoir hinders quantifications of cells with inducible provirus able to generate infectious viruses. Some ECs are able to long-term control the provirus in heterochromatin, either by targeting the integrants to repressed regions or, more likely, by eliminating the integrants in active regions and retaining the non-expressed proviruses (Jiang et al, 2020).

Results

Conclusion