Interaction of human immunodeficiency virus gp120 with the voltage‐gated potassium channel BEC1

Herrmann, Madeleine; Ruprecht, Klemens; Sauter, Marlies; Martinez, Javier P; Heteren, Pearl van; Glas, Michael; Best, Barbara; Meyerhans, Andreas; Roemer, Klaus; Mueller‐Lantzsch, Nikolaus

doi:10.1016/j.febslet.2010.07.016

Cited by 7 publications

(5 citation statements)

References 23 publications

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“…Further studies using inside-out patch clamping confirmed Nef-mediated inhibition of large-conductance Ca 2+ -dependent K + channels (BK Ca ) [21,22], but the effects of BK Ca modulation during the HIV-1 life cycle were not investigated [16]. HIV-1 gp120 and viral protein U (Vpu) have also been shown to affect K + channel activity, which is 2+ release via two-pore Ca 2+ channels (TPC) 1 and 2.…”

Section: Ion Channels and Virus Persistencementioning

confidence: 99%

“…Gp120 binding to the cytoplasmic C terminus of the ether-a-go-go (hERG) K + channel (also known as K v 11.1) and its subsequent inhibition enhanced virus particle release, which could be blocked by hERG channel overexpression [21]. HIV-1 Vpu was also reported to manipulate the resting membrane potential through interference with background leak K + channels [23,24].…”

Section: Ion Channels and Virus Persistencementioning

confidence: 99%

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Viral dependence on cellular ion channels – an emerging anti-viral target?

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Foster

Barr

et al. 2017

Journal of General Virology

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The broad range of cellular functions governed by ion channels represents an attractive target for viral manipulation. Indeed, modulation of host cell ion channel activity by viral proteins is being increasingly identified as an important virus-host interaction. Recent examples have demonstrated that virion entry, virus egress and the maintenance of a cellular environment conducive to virus persistence are, in part, dependent on virus manipulation of ion channel activity. Most excitingly, evidence has emerged that targeting ion channels pharmacologically can impede virus life cycles. Here, we discuss current examples of virus-ion channel interactions and the potential of targeting ion channel function as a new, pharmacologically safe and broad-ranging anti-viral therapeutic strategy.

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Section: Ion Channels and Virus Persistencementioning

confidence: 99%

Section: Ion Channels and Virus Persistencementioning

confidence: 99%

Viral dependence on cellular ion channels – an emerging anti-viral target?

Hover

Foster

Barr

et al. 2017

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…For example, the Hepatitis C virus non-structural protein NS5A modulates the function of Kv2.1, a voltage-gated K + channel 27 and regulates cell apoptosis. HIV-1 protein Nef alters the intracellular K + ion concentration 30 by targeting large-conductance Ca 2+ -dependent K + channels (BK Ca ) 31 whereas viral Env protein, gp120 inhibits the voltage-gated K + channel (BEC1) activity resulting in decreased virus release 32 . HIV gp120 induces hippocampal neuronal apoptosis by enhancement of Kv channel functions through p38 MAPK phosphorylation in HIV associated neurocognitive disorder 33 .…”

Section: Introductionmentioning

confidence: 99%

G protein-coupled and ATP-sensitive inwardly rectifying potassium ion channels are essential for HIV entry

Dubey

Mishra

Gaur

2019

Sci Rep

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The high genetic diversity of Human Immunodeficiency virus (HIV), has hindered the development of effective vaccines or antiviral drugs against it. Hence, there is a continuous need for identification of new antiviral targets. HIV exploits specific host proteins also known as HIV-dependency factors during its replication inside the cell. Potassium channels play a crucial role in the life cycle of several viruses by modulating ion homeostasis, cell signaling, cell cycle, and cell death. In this study, using pharmacological tools, we have identified that HIV utilizes distinct cellular potassium channels at various steps in its life cycle. Members of inwardly rectifying potassium (Kir) channel family, G protein-coupled (GIRK), and ATP-sensitive (KATP) are involved in HIV entry. Blocking these channels using specific inhibitors reduces HIV entry. Another member, Kir 1.1 plays a role post entry as inhibiting this channel inhibits virus production and release. These inhibitors are not toxic to the cells at the concentration used in the study. We have further identified the possible mechanism through which these potassium channels regulate HIV entry by using a slow-response potential-sensitive probe DIBAC4(3) and have observed that blocking these potassium channels inhibits membrane depolarization which then inhibits HIV entry and virus release as well. These results demonstrate for the first time, the important role of Kir channel members in HIV-1 infection and suggest that these K+ channels could serve as a safe therapeutic target for treatment of HIV/AIDS.

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“…G-protein coupled receptors are also associated with ion channel activity [ 374 ]. R5-gp120 can suppress the activity of the voltage gated K + channel BEC1 in 293 T cells [ 377 ] and X4-tropic envelope can increase the phosphorylation of Kv1.3 channels and induce membrane depolarization in T-cell lines [ 378 ]. In human macrophages, X4 and R5 gp120 can elicit Ca 2+ -activated K + currents, Cl − currents, and Ca 2+ -permeant nonselective cation currents, which are blocked by the specific CXCR4 antagonist, AMD3100, or in cells from donors homozygous for the CCR5- 32 mutation, respectively [ 374 , 379 ].…”

Section: Hiv Activation Of Co-receptorsmentioning

confidence: 99%

Co-receptor signaling in the pathogenesis of neuroHIV

et al. 2021

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The HIV co-receptors, CCR5 and CXCR4, are necessary for HIV entry into target cells, interacting with the HIV envelope protein, gp120, to initiate several signaling cascades thought to be important to the entry process. Co-receptor signaling may also promote the development of neuroHIV by contributing to both persistent neuroinflammation and indirect neurotoxicity. But despite the critical importance of CXCR4 and CCR5 signaling to HIV pathogenesis, there is only one therapeutic (the CCR5 inhibitor Maraviroc) that targets these receptors. Moreover, our understanding of co-receptor signaling in the specific context of neuroHIV is relatively poor. Research into co-receptor signaling has largely stalled in the past decade, possibly owing to the complexity of the signaling cascades and functions mediated by these receptors. Examining the many signaling pathways triggered by co-receptor activation has been challenging due to the lack of specific molecular tools targeting many of the proteins involved in these pathways and the wide array of model systems used across these experiments. Studies examining the impact of co-receptor signaling on HIV neuropathogenesis often show activation of multiple overlapping pathways by similar stimuli, leading to contradictory data on the effects of co-receptor activation. To address this, we will broadly review HIV infection and neuropathogenesis, examine different co-receptor mediated signaling pathways and functions, then discuss the HIV mediated signaling and the differences between activation induced by HIV and cognate ligands. We will assess the specific effects of co-receptor activation on neuropathogenesis, focusing on neuroinflammation. We will also explore how the use of substances of abuse, which are highly prevalent in people living with HIV, can exacerbate the neuropathogenic effects of co-receptor signaling. Finally, we will discuss the current state of therapeutics targeting co-receptors, highlighting challenges the field has faced and areas in which research into co-receptor signaling would yield the most therapeutic benefit in the context of HIV infection. This discussion will provide a comprehensive overview of what is known and what remains to be explored in regard to co-receptor signaling and HIV infection, and will emphasize the potential value of HIV co-receptors as a target for future therapeutic development.

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Interaction of human immunodeficiency virus gp120 with the voltage‐gated potassium channel BEC1

Cited by 7 publications

References 23 publications

Viral dependence on cellular ion channels – an emerging anti-viral target?

Viral dependence on cellular ion channels – an emerging anti-viral target?

G protein-coupled and ATP-sensitive inwardly rectifying potassium ion channels are essential for HIV entry

Co-receptor signaling in the pathogenesis of neuroHIV

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