The HIV-1 Accessory Protein Vpu Downregulates Peroxisome Biogenesis

MBio
Zaikun XuTom C Hobman

Abstract

Human immunodeficiency virus type 1 (HIV-1) establishes lifelong infections in humans, a process that relies on its ability to thwart innate and adaptive immune defenses of the host. Recently, we reported that HIV-1 infection results in a dramatic reduction of the cellular peroxisome pool. Peroxisomes are metabolic organelles that also function as signaling platforms in the innate immune response. Here, we show that the HIV-1 accessory protein Vpu is necessary and sufficient for the depletion of cellular peroxisomes during infection. Vpu induces the expression of four microRNAs that target mRNAs encoding proteins required for peroxisome formation and metabolic function. The ability of Vpu to downregulate peroxisomes was found to be dependent upon the Wnt/β-catenin signaling pathway. Given the importance of peroxisomes in innate immune signaling and central nervous system function, the roles of Vpu in dampening antiviral signaling appear to be more diverse than previously realized. Finally, our findings highlight a potential role for Wnt/β-catenin signaling in peroxisome homeostasis through modulating the production of biogenesis factors.IMPORTANCE People living with HIV can experience accelerated aging and the development of ne...Continue Reading

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Citations

Jul 7, 2020·International Journal of Molecular Medicine·Felician StancioiuAristidis Tsatsakis
May 28, 2020·MBio·Kristina Hopfensperger, Daniel Sauter
Oct 14, 2020·Trends in Biochemical Sciences·Shanmuga S MahalingamSuresh Subramani
Dec 22, 2020·Frontiers in Microbiology·Pavitra RamdasAjit Chande
May 20, 2021·Molecular Biology of the Cell·Barbara KnoblachRichard A Rachubinski

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Methods Mentioned

BETA
confocal microscopy
PCR
transfection
PCRs
protein assay

Software Mentioned

Excel
Volocity
Imaris

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