HIV-1 Nef: a master manipulator of the membrane trafficking machinery mediating immune evasion

Pawlak, Emily N.; Dikeakos, Jimmy D.

doi:10.1016/j.bbagen.2015.01.003

Cited by 60 publications

(72 citation statements)

References 103 publications

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“…21) or the ability to respond in scenarios in which HLAs are differentially manipulated by a virus such as HIV (reviewed in Ref. 22). There are no studies indicating a functional interaction of LILRA1 with MHC-I with cells naturally expressing LILRA1, but it would be expected to counterbalance LILRB1 and -B2 signals in cells that coexpress the receptors, such as monocytes/macrophages and dendritic cells.…”

Section: Interaction With Native Classical Mhc-imentioning

confidence: 99%

The Expanding Spectrum of Ligands for Leukocyte Ig-like Receptors

Burshtyn

Morcos

2016

The Journal of Immunology

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The human leukocyte Ig-like receptor family is part of the paired receptor system. The receptors are widely expressed by various immune cells, and new functions continue to emerge. Understanding the range of functions of the receptors is of general interest because several types of pathogens exploit the receptors and genetic diversity of the receptors has been linked to various autoimmune diseases. Class I major histocompatibility molecules were the first ligands appreciated for these receptors, but the types of ligands identified over the last several years are quite diverse, including intact pathogens, immune-modulatory proteins, and molecules normally found within the CNS. This review focuses on the types of ligands described to date, how the individual receptors bind to several distinct types of ligands, and the known functional consequences of those interactions.

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Section: Interaction With Native Classical Mhc-imentioning

confidence: 99%

The Expanding Spectrum of Ligands for Leukocyte Ig-like Receptors

Burshtyn

Morcos

2016

The Journal of Immunology

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“…The HIV-1 accessory protein Nef uses a bipartite motif composed of a short acidic cluster and the αB helix to interact with both PACS-1 and PACS-2 (Piguet et al, 2000;Atkins et al, 2008;Dikeakos et al, 2012). This bipartite binding enables HIV-1 Nef to downregulate major histocompatibility complex class I (MHC-I) from the cell surface, which allows the virus to escape immune detection (Pawlak and Dikeakos, 2015) (Fig. 3B).…”

Section: Introductionmentioning

confidence: 99%

“…For example, in obese mice challenged by a high-fat diet, PACS-2 is responsible for a chronic increase in MAM formation (Arruda et al, 2014), leading to toxic mitochondrial Ca 2+ overload that consequently impairs mitochondrial oxidative capacity, exacerbates insulin The steps shown here depict the 'signaling mode' of HIV-1 Nef-induced immune evasion, which HIV-1 implements during the first 48 h post infection. A detailed discussion of Nef-induced immune evasion is presented elsewhere (Dikeakos et al, 2010;Pawlak and Dikeakos 2015).…”

Section: Introductionmentioning

confidence: 99%

Caught in the act – protein adaptation and the expanding roles of the PACS proteins in tissue homeostasis and disease

Thomas

Aslan

Thomas

et al. 2017

Journal of Cell Science

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Vertebrate proteins that fulfill multiple and seemingly disparate functions are increasingly recognized as vital solutions to maintaining homeostasis in the face of the complex cell and tissue physiology of higher metazoans. However, the molecular adaptations that underpin this increased functionality remain elusive. In this Commentary, we review the PACS proteins -which first appeared in lower metazoans as protein traffic modulators and evolved in vertebrates to integrate cytoplasmic protein traffic and interorganellar communication with nuclear gene expression -as examples of protein adaptation 'caught in the act'. Vertebrate PACS-1 and PACS-2 increased their functional density and roles as metabolic switches by acquiring phosphorylation sites and nuclear trafficking signals within disordered regions of the proteins. These findings illustrate one mechanism by which vertebrates accommodate their complex cell physiology with a limited set of proteins. We will also highlight how pathogenic viruses exploit the PACS sorting pathways as well as recent studies on PACS genes with mutations or altered expression that result in diverse diseases. These discoveries suggest that investigation of the evolving PACS protein family provides a rich opportunity for insight into vertebrate cell and organ homeostasis.

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“…Specifically, we and others have demonstrated that Nef manipulates the host cell membrane trafficking machinery to downregulate multiple cell surface receptors, including CD4 and MHC-I [74,75,76]. Indeed, the downregulation of MHC-I from the cell surface by Nef is a central host cell-hijacking event of HIV-1 infection (reviewed by Pawlak and Dikeakos [74]).…”

Section: Trespassing Into Enemy Territory: Imaging Host Cell Hijacmentioning

confidence: 99%

“…Indeed, the downregulation of MHC-I from the cell surface by Nef is a central host cell-hijacking event of HIV-1 infection (reviewed by Pawlak and Dikeakos [74]). Correspondingly, Nef trafficking and function depend extensively on overtaking a plethora of host cellular proteins, resulting in a multitude of viral–host interactions within the HIV-1 lifecycle, and will serve as the model for the techniques discussed below.…”

Section: Trespassing Into Enemy Territory: Imaging Host Cell Hijacmentioning

confidence: 99%

Where in the Cell Are You? Probing HIV-1 Host Interactions through Advanced Imaging Techniques

Dirk

Nynatten

Dikeakos

2016

Viruses

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Viruses must continuously evolve to hijack the host cell machinery in order to successfully replicate and orchestrate key interactions that support their persistence. The type-1 human immunodeficiency virus (HIV-1) is a prime example of viral persistence within the host, having plagued the human population for decades. In recent years, advances in cellular imaging and molecular biology have aided the elucidation of key steps mediating the HIV-1 lifecycle and viral pathogenesis. Super-resolution imaging techniques such as stimulated emission depletion (STED) and photoactivation and localization microscopy (PALM) have been instrumental in studying viral assembly and release through both cell–cell transmission and cell–free viral transmission. Moreover, powerful methods such as Forster resonance energy transfer (FRET) and bimolecular fluorescence complementation (BiFC) have shed light on the protein-protein interactions HIV-1 engages within the host to hijack the cellular machinery. Specific advancements in live cell imaging in combination with the use of multicolor viral particles have become indispensable to unravelling the dynamic nature of these virus-host interactions. In the current review, we outline novel imaging methods that have been used to study the HIV-1 lifecycle and highlight advancements in the cell culture models developed to enhance our understanding of the HIV-1 lifecycle.

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HIV-1 Nef: a master manipulator of the membrane trafficking machinery mediating immune evasion

Cited by 60 publications

References 103 publications

The Expanding Spectrum of Ligands for Leukocyte Ig-like Receptors

The Expanding Spectrum of Ligands for Leukocyte Ig-like Receptors

Caught in the act – protein adaptation and the expanding roles of the PACS proteins in tissue homeostasis and disease

Where in the Cell Are You? Probing HIV-1 Host Interactions through Advanced Imaging Techniques

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