Alterations in intracellular potassium concentration by HIV-1 and SIV Nef

Choi, Bok Kyoung; Fermin, César D.; Comardelle, Alla M; Haislip, Allyson M.; Voss, Thomas G.; Garry, Robert F.

doi:10.1186/1743-422x-5-60

Cited by 11 publications

(9 citation statements)

References 35 publications

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“…Somewhat surprisingly, given the critical importance of ion channels for cell function, there are few examples of viral modu-lation of host cell ion channel activity. Of note, the HIV-1 Nef protein, which like NS5A also possesses polyproline motifs known to interact with cellular SH3 domains (24), has been demonstrated to affect cellular K ϩ levels (25,26) and inactivate an undefined large-conductance K ϩ channel in U251 glioma cells (27), although these effects have not been shown to have any role in the virus lifecycle. It is pertinent to note that Nef has been demonstrated to bind to and inhibit an upstream p38 MAPK kinase, apoptosis signal-regulating kinase-1 (ASK-1) (28), which has also been shown to play a role in the apoptotic function of Kv2.1 (29).…”

Section: Discussionmentioning

confidence: 99%

Suppression of a pro-apoptotic K⁺channel as a mechanism for hepatitis C virus persistence

Mankouri

Dallas

Hughes

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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An estimated 3% of the global population are infected with hepatitis C virus (HCV), and the majority of these individuals will develop chronic liver disease. As with other chronic viruses, establishment of persistent infection requires that HCV-infected cells must be refractory to a range of pro-apoptotic stimuli. In response to oxidative stress, amplification of an outward K ϩ current mediated by the Kv2.1 channel, precedes the onset of apoptosis. We show here that in human hepatoma cells either infected with HCV or harboring an HCV subgenomic replicon, oxidative stress failed to initiate apoptosis via Kv2.1. The HCV NS5A protein mediated this effect by inhibiting oxidative stress-induced p38 MAPK phosphorylation of Kv2

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Section: Discussionmentioning

confidence: 99%

Suppression of a pro-apoptotic K⁺channel as a mechanism for hepatitis C virus persistence

Mankouri

Dallas

Hughes

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…HIV-1 primarily exhibits tropism for CD4(+) T lymphocytes (T cells) in which the HIV-1 accessory protein Nef has been shown to indirectly alter K + concentrations [20]. 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].…”

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

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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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“…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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Alterations in intracellular potassium concentration by HIV-1 and SIV Nef

Cited by 11 publications

References 35 publications

Suppression of a pro-apoptotic K⁺channel as a mechanism for hepatitis C virus persistence

Suppression of a pro-apoptotic K⁺channel as a mechanism for hepatitis C virus persistence

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

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Alterations in intracellular potassium concentration by HIV-1 and SIV Nef

Cited by 11 publications

References 35 publications

Suppression of a pro-apoptotic K+channel as a mechanism for hepatitis C virus persistence

Suppression of a pro-apoptotic K+channel as a mechanism for hepatitis C virus persistence

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

Contact Info

Product

Resources

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Suppression of a pro-apoptotic K⁺channel as a mechanism for hepatitis C virus persistence

Suppression of a pro-apoptotic K⁺channel as a mechanism for hepatitis C virus persistence