The Role of ERK1/2 Signaling Pathway in Nef Protein Upregulation of the Expression of the Intercellular Adhesion Molecule 1 in Endothelial Cells

Yang, Fan; Liu, Chaoqi; Qin, Xiaoli; Wang, Yanlin; Yu, Han; Zhou, Yuan‐Guo

doi:10.1177/0003319710364215

Cited by 10 publications

(3 citation statements)

References 24 publications

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“…Nef-expressing T cells demonstrate enhanced adherence to ECs as observed by their impaired diapedesis and migration into the subendothelial space (126). Fan et al have shown ERK kinase-mediated ICAM-1 upregulation in vascular ECs stably expressing Nef (54). Furthermore, Nef increases endothelial MCP-1 production through activation of the NF-kB signaling pathway (50).…”

Section: Hiv Encoded Proteins and Endothelial Dysfunctionmentioning

confidence: 99%

HIV Proteins and Endothelial Dysfunction: Implications in Cardiovascular Disease

Anand

Rachel

Parthasarathy

2018

Front. Cardiovasc. Med.

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With the success of antiretroviral therapy (ART), a dramatic decrease in viral burden and opportunistic infections and an increase in life expectancy has been observed in human immunodeficiency virus (HIV) infected individuals. However, it is now clear that HIV- infected individuals have enhanced susceptibility to non-AIDS (Acquired immunodeficiency syndrome)-related complications such as cardiovascular disease (CVD). CVDs such as atherosclerosis have become a significant cause of morbidity and mortality in individuals with HIV infection. Though studies indicate that ART itself may increase the risk to develop CVD, recent studies suggest a more important role for HIV infection in contributing to CVD independently of the traditional risk factors. Endothelial dysfunction triggered by HIV infection has been identified as a critical link between infection, inflammation/immune activation, and atherosclerosis. Considering the inability of HIV to actively replicate in endothelial cells, endothelial dysfunction depends on both HIV-encoded proteins as well as inflammatory mediators released in the microenvironment by HIV-infected cells. Indeed, the HIV proteins, gp120 (envelope glycoprotein) and Tat (transactivator of transcription), are actively secreted into the endothelial cell micro-environment during HIV infection, while Nef can be actively transferred onto endothelial cells during HIV infection. These proteins can have significant direct effects on the endothelium. These include a range of responses that contribute to endothelial dysfunction, including enhanced adhesiveness, permeability, cell proliferation, apoptosis, oxidative stress as well as activation of cytokine secretion. This review summarizes the current understanding of the interactions of HIV, specifically its proteins with endothelial cells and its implications in cardiovascular disease. We analyze recent in vitro and in vivo studies examining endothelial dysfunction in response to HIV proteins. Furthermore, we discuss the multiple mechanisms by which these viral proteins damage the vascular endothelium in HIV patients. A better understanding of the molecular mechanisms of HIV protein associated endothelial dysfunction leading to cardiovascular disease is likely to be pivotal in devising new strategies to treat and prevent cardiovascular disease in HIV-infected patients.

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Section: Hiv Encoded Proteins and Endothelial Dysfunctionmentioning

confidence: 99%

HIV Proteins and Endothelial Dysfunction: Implications in Cardiovascular Disease

Anand

Rachel

Parthasarathy

2018

Front. Cardiovasc. Med.

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“…Invasion of the brain by leukocytes would additionally require an upregulation of adhesion molecules on both endothelial and infected cells. Indeed, it has been shown that HIV Nef upregulates the intercellular adhesion molecule 1 (ICAM-1) in vascular endothelial cells (95). ICAM-1 interacts with the lymphocyte function-associated antigen 1 (LFA-1), and its subunits, CD11a and CD18, are upregulated in HIV-infected monocytes (96, 97).…”

Section: Nef-induced Ccl2 Expression and The Function Of The Blood-brmentioning

confidence: 99%

Nef-induced CCL2 Expression Contributes to HIV/SIV Brain Invasion and Neuronal Dysfunction

Lehmann

Erfle

2019

Front. Immunol.

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C-C motif chemokine ligand 2 (CCL2) is a chemoattractant for leukocytes including monocytes, T cells, and natural killer cells and it plays an important role in maintaining the integrity and function of the brain. However, there is accumulating evidence that many neurological diseases are attributable to a dysregulation of CCL2 expression. Acquired immune deficiency syndrome (AIDS) encephalopathy is a severe and frequent complication in individuals infected with the human immunodeficiency virus (HIV) or the simian immunodeficiency virus (SIV). The HIV and SIV Nef protein, a progression factor in AIDS pathology, can be transferred by microvesicles including exosomes and tunneling nanotubes (TNT) within the host even to uninfected cells, and Nef can induce CCL2 expression. This review focuses on findings which collectively add new insights on how Nef-induced CCL2 expression contributes to neurotropism and neurovirulence of HIV and SIV and elucidates why adjuvant targeting of CCL2 could be a therapeutic option for HIV-infected persons.

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“…Finally, as mentioned above, infectivity of HIV particles is enhanced by incorporation of ICAM-1 due to the binding with LFA-1 on the target cells [89, 90]. Recently, it was demonstrated that ICAM-1 expression is up-regulated by Nef in a vascular endothelial cell line [95], opening perspectives for a possible cellular target protein of Nef involved in infectivity. Therefore, studies analyzing the incorporation and exclusion of host proteins in virions produced from HIV-infected primary cells with or without Nef might reveal new insights in the mechanism of Nef enhanced infectivity.…”

Section: Mechanism Of Infectivity Enhancement By Nefmentioning

confidence: 99%

The Nef-Infectivity Enigma: Mechanisms of Enhanced Lentiviral Infection

Vermeíre¹,

Vanbillemont²,

Witkowski³

et al. 2011

CHR

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The Nef protein is an essential factor for lentiviral pathogenesis in humans and other simians. Despite a multitude of functions attributed to this protein, the exact role of Nef in disease progression remains unclear. One of its most intriguing functions is the ability of Nef to enhance the infectivity of viral particles. In this review we will discuss current insights in the mechanism of this well-known, yet poorly understood Nef effect. We will elaborate on effects of Nef, on both virion biogenesis and the early stage of the cellular infection, that might be involved in infectivity enhancement. In addition, we provide an overview of different HIV-1 Nef domains important for optimal infectivity and briefly discuss some possible sources of the frequent discrepancies in the field. Hereby we aim to contribute to a better understanding of this highly conserved and therapeutically attractive Nef function.

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The Role of ERK1/2 Signaling Pathway in Nef Protein Upregulation of the Expression of the Intercellular Adhesion Molecule 1 in Endothelial Cells

Cited by 10 publications

References 24 publications

HIV Proteins and Endothelial Dysfunction: Implications in Cardiovascular Disease

HIV Proteins and Endothelial Dysfunction: Implications in Cardiovascular Disease

Nef-induced CCL2 Expression Contributes to HIV/SIV Brain Invasion and Neuronal Dysfunction

The Nef-Infectivity Enigma: Mechanisms of Enhanced Lentiviral Infection

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