Recombinant nef HIV-IIIB protein is toxic to human neurons in culture

Trillo-Pazos, Gusta; McFarlane-Abdulla, Elizabeth; Campbell, Iain C.; Pilkington, Geoffrey J.; Everall, Ian

doi:10.1016/s0006-8993(00)02213-7

Cited by 84 publications

(64 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with reports that HIV proteins, including Tat, Vpr, gp41 and Nef, can initiate apoptotic cascades in other neural cell types (Adamson et al, 1996;Yang et al, 1997;Kruman et al, 1998;Bartz and Emerman, 1999;Liu et al, 2000;Trillo-Pazos et al, 2000;Parrish et al, 2001;Li et al, 2001). The protective role of caspase inhibitors in experimental models of HIVE supports the involvement of caspases in the pathogenesis of neuroAIDS (Garden et al, 2002).…”

Section: Discussionsupporting

confidence: 90%

“…Apoptotic changes are seen with HIVE in both neurons and nonneuronal cells (Ramirez et al, 2001;Bonavia et al, 2001;Corasaniti et al, 2001;AdleBiassette et al, 1995;Gelbard et al, 1995;Petito and Roberts, 1995;Shi et al, 1996;Kaul et al, 2001;Shi et al, 1998;Park et al, 2001). HIV-1 is neurotoxic by inducing inflammation and through the direct release of toxic viral proteins such as Nef, Vpr, gp120 and Tat (Haughey et al, 2001;Brenneman et al, 1988;Dreyer et al, 1990;Adamson et al, 1996;New et al, 1997;Kruman et al, 1998;Yeung et al, 1998;Huang and Bond, 2000;Trillo-Pazos et al, 2000;Nath, 2002). The neurotoxicity of gp120 has been demonstrated both in primary human neuronal cultures (Lannuzel et al, 1997;Yeung et al, 1995) and in transgenic mice (Toggas et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Apoptotic death of striatal neurons induced by human immunodeficiency virus-1 Tat and gp120: Differential involvement of caspase-3 and endonuclease G

et al. 2004

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Apoptotic death of striatal neurons induced by human immunodeficiency virus-1 Tat and gp120: Differential involvement of caspase-3 and endonuclease G

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Moreover, patch-clamp experiments have shown Nef reversibly increases the total K + current in chick dorsal root ganglions (Werner et al 1991), allowing for the possibility of a direct link between HIV-1-encoded viral protein and increased potassium channel current. Notably, the finding that the direct application of Nef exhibits neurotoxic effects on cultured human neurons (Trillo-Pazos et al 2000), possibly through excessive K + efflux, would seem to further support this view.…”

Section: Hiv-1 Protein Nefmentioning

confidence: 87%

Voltage-gated Potassium Channels in Human Immunodeficiency Virus Type-1 (HIV-1)-associated Neurocognitive Disorders

Keblesh

Xiong

2008

J Neuroimmune Pharmacol

View full text Add to dashboard Cite

Human immunodeficiency virus type-1 (HIV-1)-associated dementia (HAD), a severe form of HIV-associated neurocognitive disorders (HAND), describes the cognitive impairments and behavioral disturbances which afflict many HIV-infected individuals. Although the precise mechanism leading to HAD is incompletely understood, it is commonly accepted its progression involves a critical mass of infected and activated mononuclear phagocytes (brain perivascular macrophages and microglia) releasing immune and viral products in the brain. These cellular and viral products induce neuronal dysfunction and injury via various signaling pathways. Emerging evidence indicates voltage-gated potassium (K v ) channels, key regulators of cell excitability and animal behavior (learning and memory), are involved in the pathogenesis of HAD/HAND. Here we survey the literature and find that HAD-related alterations in cellular and viral products can increase neuronal K v channel activity, leading to neuronal dysfunction and cognitive deficits. Thus, neuronal K v channels may be a new target in the effort to develop therapies for HAD and perhaps other inflammatory neurodegenerative disorders.

show abstract

“…11,65,66 In vitro, Nef is lethal to neurons and glial cells in nanomolar concentrations and can increase the expression of MMPs, thus potentially modifying the permeability of the blood-brain barrier. 67,68 Nef has significant sequence homology with scorpion neurotoxins and like these venoms can cause the inactivation of a large-conductance potassium channels. [69][70][71] Based on these findings, it has been suggested that Nef contributes to the neuronal degeneration seen in HIV encephalitis.…”

Section: Neurotoxic Viral Proteinsmentioning

confidence: 99%

Cell death in HIV dementia

2005

View full text Add to dashboard Cite

Many patients infected with human immunodeficiency virus type-1 (HIV-1) suffer cognitive impairment ranging from mild to severe (HIV dementia), which may result from neuronal death in the basal ganglia, cerebral cortex and hippocampus. HIV-1 does not kill neurons by infecting them. Instead, viral proteins released from infected glial cells, macrophages and/ or stem cells may directly kill neurons or may increase their vulnerability to other cell death stimuli. By binding to and/or indirectly activating cell surface receptors such as CXCR4 and the N-methyl-D-aspartate receptor, the HIV-1 proteins gp120 and Tat may trigger neuronal apoptosis and excitotoxicity as a result of oxidative stress, perturbed cellular calcium homeostasis and mitochondrial alterations. Membrane lipid metabolism and inflammation may also play important roles in determining whether neurons live or die in HIV-1-infected patients. Drugs and diets that target oxidative stress, excitotoxicity, inflammation and lipid metabolism are in development for the treatment of HIV-1 patients.

show abstract

Recombinant nef HIV-IIIB protein is toxic to human neurons in culture

Cited by 84 publications

References 42 publications

Apoptotic death of striatal neurons induced by human immunodeficiency virus-1 Tat and gp120: Differential involvement of caspase-3 and endonuclease G

Apoptotic death of striatal neurons induced by human immunodeficiency virus-1 Tat and gp120: Differential involvement of caspase-3 and endonuclease G

Voltage-gated Potassium Channels in Human Immunodeficiency Virus Type-1 (HIV-1)-associated Neurocognitive Disorders

Cell death in HIV dementia

Contact Info

Product

Resources

About