HIV-1 viral infectivity factor interacts with microtubule-associated protein light chain 3 and inhibits autophagy

Borel, Sophie; Robert-Hebmann, Véronique; Alfaisal, Jamal; Jain, Ashish; Faure, Mathias; Espert, Lucile; Chaloin, Laurent; Paillart, Jean-Christophe; Johansen, Terje; Biard-Piechaczyk, Martine

doi:10.1097/qad.0000000000000554

Cited by 53 publications

(49 citation statements)

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“…44 Recently, HIV-Vif has been demonstrated to restrict autophagy by interacting with MAP1LC3B in productively infected CD4 C T cells. 45 Furthermore, Sagnier et al report induction of autophagy-dependent apoptosis of uninfected bystander CD4 C T cells by envelope (Env) glycoprotein. 44 In contrast, Env protein does not induce autophagy in uninfected macrophages and autophagy is necessary for virus replication in these cells.…”

Section: Discussionmentioning

confidence: 99%

Enhanced autophagy in pulmonary endothelial cells on exposure to HIV-Tat and morphine: Role in HIV-related pulmonary arterial hypertension

et al. 2016

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Intravenous drug use is one of the major risk factors for HIV-infection in HIV-related pulmonary arterial hypertension patients. We previously demonstrated exaggerated pulmonary vascular remodeling with enhanced apoptosis followed by increased proliferation of pulmonary endothelial cells on simultaneous exposure to both opioids and HIV protein(s). Here we hypothesize that the exacerbation of autophagy may be involved in the switching of endothelial cells from an early apoptotic state to later hyperproliferative state. Treatment of human pulmonary microvascular endothelial cells (HPMECs) with both the HIV-protein Tat and morphine resulted in an oxidative stress-dependent increase in the expression of various markers of autophagy and formation of autophagosomes when compared to either Tat or morphine monotreatments as demonstrated by western blot, transmission electron microscopy and immunofluorescence. Autophagy flux experiments suggested increased formation rather than decreased clearance of autolysosomes. Inhibition of autophagy resulted in a significant increase in apoptosis and reduction in proliferation of HPMECs with combined morphine and Tat (MCT) treatment compared to monotreatments whereas stimulation of autophagy resulted in opposite effects. Significant increases in the expression of autophagy markers as well as the number of autophagosomes and autolysosomes was observed in the lungs of SIV-infected macaques and HIV-infected humans exposed to opioids. Overall our findings indicate that morphine in combination with viral protein(s) results in the induction of autophagy in pulmonary endothelial cells that may lead to an increase in severity of angio-proliferative remodeling of the pulmonary vasculature on simian and human immunodeficiency virus infection in the presence of opioids.

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Section: Discussionmentioning

confidence: 99%

Enhanced autophagy in pulmonary endothelial cells on exposure to HIV-Tat and morphine: Role in HIV-related pulmonary arterial hypertension

et al. 2016

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“…However, despite autophagy being an innate antiviral defense mechanism, viruses may also hijack autophagy for their efficient replication in a celltype and virus specific manner. HIV utilizes autophagosomal membranes as a scaffold for Gag processing and the production of nascent virions (6), while controlling the antiviral proteolytic and degradative late stages of autophagy to avoid its own degradation (6,7,58,59). To our knowledge, these data are the first to describe the effect of a dual PI3K/MTOR inhibitor or PI3K/MTOR/BRD4 inhibitor on HIV infection of macrophages, an important site of HIV infection and persistence.…”

Section: Discussionmentioning

confidence: 99%

Induction of autophagy by PI3K/MTOR and PI3K/MTOR/BRD4 inhibitors suppresses HIV-1 replication

Campbell

Bruckman

Herns

et al. 2018

Journal of Biological Chemistry

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“…MAP proteins have also been linked to cellular processes such as phagocytosis and autophagy, which are both repressed in HIV-1 target cells, macrophages and T lymphocytes, respectively. Two HIV-1 proteins were recently shown to play an inhibitory role in these processes: Vpr was shown to interact with EB1 and p150 glued , perturbing their MT plus end localization, thus altering phagosome movement and maturation (107), while Vif was shown to interact directly with LC3B, a major autophagy component (108). In this context, the study of MAP1S will prove an interesting topic, since MAP1S is involved both in autophagy, regulating autophagosomal biogenesis and degradation, and interacting with autophagosome-associated LC3 of MAP1A and MAP1B (109), and in bacterial phagocytosis by macrophages through interaction with MyD88 a key adaptor of Toll-like receptors (110).…”

Section: Resultsmentioning

confidence: 99%

Role of non-motile microtubule-associated proteins in virus trafficking

Portilho

Persson²,

Arhel

2016

Biomolecular Concepts

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Viruses are entirely dependent on their ability to infect a host cell in order to replicate. To reach their site of replication as rapidly and efficiently as possible following cell entry, many have evolved elaborate mechanisms to hijack the cellular transport machinery to propel themselves across the cytoplasm. Long-range movements have been shown to involve motor proteins along microtubules (MTs) and direct interactions between viral proteins and dynein and/or kinesin motors have been well described. Although less well-characterized, it is also becoming increasingly clear that non-motile microtubule-associated proteins (MAPs), including structural MAPs of the MAP1 and MAP2 families, and microtubule plus-end tracking proteins (+ TIPs), can also promote viral trafficking in infected cells, by mediating interaction of viruses with filaments and/or motor proteins, and modulating filament stability. Here we review our current knowledge on nonmotile MAPs, their role in the regulation of cytoskeletal dynamics and in viral trafficking during the early steps of infection.

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HIV-1 viral infectivity factor interacts with microtubule-associated protein light chain 3 and inhibits autophagy

Abstract: Our study unveils that Vif inhibits autophagy independently of its action on APOBEC3G and, therefore, suggest a new function of this viral protein in restricting innate antiviral mechanisms.

Cited by 53 publications

References 54 publications

Enhanced autophagy in pulmonary endothelial cells on exposure to HIV-Tat and morphine: Role in HIV-related pulmonary arterial hypertension

Enhanced autophagy in pulmonary endothelial cells on exposure to HIV-Tat and morphine: Role in HIV-related pulmonary arterial hypertension

Induction of autophagy by PI3K/MTOR and PI3K/MTOR/BRD4 inhibitors suppresses HIV-1 replication

Role of non-motile microtubule-associated proteins in virus trafficking

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