HIV life cycle, innate immunity and autophagy in the central nervous system

Meulendyke, Kelly A.; Croteau, Joshua; Zink, M. Christine

doi:10.1097/coh.0000000000000106

Cited by 15 publications

(11 citation statements)

References 65 publications

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“…If supposed antiviral candidates target these viral proteins, HIV-1 Nef, Tat and Vpr, their actions can be restrained. All the mentioned mechanisms are directly performed by retroviral molecules [15], but other mechanisms could also be triggered, such as those involved in the innate immune system, e.g. (i) the induction of toll-like receptor expression, that interacts with viral nucleic acid, or (ii) production of cytokines that stimulate the action of T cytotoxic cells, and NK cells, and even host cell expression of the major histocompatibility complex molecules, in order to present viral peptides to the other cells of the immune system [16].…”

Section: Possible Action Mechanism Of Antiviral Compoundsmentioning

confidence: 99%

“…Caerin peptides are composed of 25 amino acid residues in their structure, including four central amino acid residues not present in maculatin peptides. In lipid bilayer membranes, these peptides are adjusted to two α-helices, interlinked by a flexible hinge region limited by Pro 15 and Pro 19 , which determine the disruption of viral envelope and cell membrane [70].…”

Section: Anuran Skin Peptidesmentioning

confidence: 99%

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Antiviral activity of animal venom peptides and related compounds

Mata

Mourão

Rangel

et al. 2017

J Venom Anim Toxins Incl Trop Dis

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Viruses exhibit rapid mutational capacity to trick and infect host cells, sometimes assisted through virus-coded peptides that counteract host cellular immune defense. Although a large number of compounds have been identified as inhibiting various viral infections and disease progression, it is urgent to achieve the discovery of more effective agents. Furthermore, proportionally to the great variety of diseases caused by viruses, very few viral vaccines are available, and not all are efficient. Thus, new antiviral substances obtained from natural products have been prospected, including those derived from venomous animals. Venoms are complex mixtures of hundreds of molecules, mostly peptides, that present a large array of biological activities and evolved to putatively target the biochemical machinery of different pathogens or host cellular structures. In addition, non-venomous compounds, such as some body fluids of invertebrate organisms, exhibit antiviral activity. This review provides a panorama of peptides described from animal venoms that present antiviral activity, thereby reinforcing them as important tools for the development of new therapeutic drugs.

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Section: Possible Action Mechanism Of Antiviral Compoundsmentioning

confidence: 99%

Section: Anuran Skin Peptidesmentioning

confidence: 99%

Antiviral activity of animal venom peptides and related compounds

Mata

Mourão

Rangel

et al. 2017

J Venom Anim Toxins Incl Trop Dis

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“…HIV-1 can infect astrocytes and cause a latent infection suggesting that astrocytes can serve as viral reservoirs 14,15,16 . Nef is also known to affect neuronal cell viability 17 .…”

mentioning

confidence: 99%

Dysregulation of autophagy by HIV-1 Nef in human astrocytes

2015

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Viruses often exploit autophagy, a common cellular process of degradation of damaged proteins, organelles, and pathogens, to avoid destruction. HIV-1 dysregulates this process in several cell types by means of Nef protein. Nef is a small HIV-1 protein which is expressed abundantly in astrocytes of HIV-1-infected brains and has been suggested to have a role in the pathogenesis of HIV-Associated Neurocognitive Disorders (HAND). In order to explore its effect in the CNS with respect to autophagy, HIV-1 Nef was expressed in primary human fetal astrocytes (PHFA) using an adenovirus vector (Ad-Nef). We observed that Nef expression triggered the accumulation of autophagy markers, ATG8/LC3 and p62 (SQSMT1). Similar results were obtained with Bafilomycin A1, an autophagy inhibitor which blocks the fusion of autophagosome to lysosome. Furthermore co-expression of tandem LC3 vector (mRFP-EGFP-LC3) and Ad-Nef in these cells produced mainly yellow puncta (mRFP+, EGFP+) strongly suggesting that autophagosome fusion to lysosome is blocked in PHFA cells in the presence of Nef. Together these data indicate that HIV-1 Nef mimics Bafilomycin A1 and blocks the last step of autophagy thereby helping HIV-1 virus to avoid autophagic degradation in human astrocytes.

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“…Postmortem brains of patients with HIV-1 encephalitis exhibit an increased expression of autophagy markers, suggesting that dysregulation of autophagy might be important in the pathogenesis of HIV-1 encephalitis [2]. Additionally, in cells of monocyte/macrophage lineage, HIV-1 proteins can both promote and delay autophagy to facilitate different stages of viral replication, which might modulate the pathogenesis of HAND [3]. On the other hand, in human astrocytes, HIV-1 protein Nef blocks the last step of autophagy, which helps HIV-1 virus to avoid autophagic degradation [4].…”

Section: Introductionmentioning

confidence: 99%

HIV-1 Tat increases BAG3 via NF-κB signaling to induce autophagy during HIV-associated neurocognitive disorder

Dong

Xiang

et al. 2018

Cell Cycle

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The human immunodeficiency virus-1 (HIV-1) regulatory protein Tat plays an important role during HIV-1-associated neurocognitive disorders (HAND) by inducing neuronal autophagy. In this study, we used immunohistochemistry, immunofluorescence, western blot, qRT-PCR, and RNA interference to elucidate the involvement of Bcl-2-associated athanogene 3 (BAG3) in the pathogenesis of HIV-1 Tat-induced autophagy during HAND. We found that BAG3 expression is elevated in astrocytes in frontal cortex of macaques infected with simian immunodeficiency virus-human immunodeficiency chimeric virus (SHIV). In addition, in human primary glioblastoma cells (U87), HIV-1 Tat upregulated BAG3 in an NF-κB-dependent manner to induce autophagy. Importantly, suppression of BAG3 or inhibition of NF-κB activity reversed the HIV-1 Tat-induced autophagy. These results indicate that HIV-1 Tat induces autophagy by upregulating BAG3 via NF-κB signaling, which suggests BAG3 and NF-κB could potentially serve as novel targets for HAND therapies.

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HIV life cycle, innate immunity and autophagy in the central nervous system

Cited by 15 publications

References 65 publications

Antiviral activity of animal venom peptides and related compounds

Antiviral activity of animal venom peptides and related compounds

Dysregulation of autophagy by HIV-1 Nef in human astrocytes

HIV-1 Tat increases BAG3 via NF-κB signaling to induce autophagy during HIV-associated neurocognitive disorder

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