Bafilomycin A1 Inhibits HIV-1 Infection by Disrupting Lysosomal Cholesterol Transport

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2024 Sep 28

PMID 39339852

Authors

Byeongwoon Song

Olga Korolkova

Affiliations

Soon will be listed here.

Abstract

The productive replication of human immunodeficiency virus type 1 (HIV-1) involves intricate interactions between viral proteins and host cell machinery. However, the contributions of the lysosomal pathways for HIV-1 replication are not fully understood. The goal of this study was to determine the impact of lysosome-targeting compounds on HIV-1 replication and identify the cellular changes that are linked to HIV-1 inhibition using cell culture models of HIV-1 infection. Here, we demonstrate that the treatment of cells with various pharmacological agents known to inhibit lysosomal functions interfere with HIV-1 replication. The vacuolar ATPase (V-ATPase) inhibitor bafilomycin A1 exerted a potent inhibition of HIV-1 replication. Bafilomycin A1 inhibition of HIV-1 was independent of coreceptor tropism of HIV-1. Our data suggest that bafilomycin A1 inhibits HIV-1 at the post-integration steps of the virus life cycle, which include viral gene expression, virus assembly, and/or egress. Analysis of the cellular alterations following bafilomycin A1 treatment indicates that bafilomycin A1 causes a disruption in lysosome structure and functions. Treatment of cells with bafilomycin A1 caused an accumulation of unesterified cholesterol in lysosomes along with the expansion of the lysosomal compartments. Interestingly, the overexpression of the lysosomal cholesterol transporter Niemann-Pick type C 1 (NPC1) partially relieved bafilomycin A1 inhibition of HIV-1. Collectively, our data suggest that bafilomycin A1 inhibits HIV-1 replication in part by disrupting the lysosomal cholesterol trafficking pathway.

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