Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells

Kelsey Voss; Moushimi Amaya; Claudius Mueller; Brian Roberts; Kylene Kehn-Hall; Charles Bailey; Emanuel Petricoin; Aarthi Narayanan

doi:10.1016/j.virol.2014.09.005

Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells

Kelsey Voss, Moushimi Amaya, Claudius Mueller, Brian Roberts, Kylene Kehn-Hall, Charles Bailey, Emanuel Petricoin, Aarthi Narayanan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated in Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses.

Original language	English
Pages (from-to)	490-503
Number of pages	14
Journal	Virology
Volume	468
DOIs	https://doi.org/10.1016/j.virol.2014.09.005
State	Published - 1 Nov 2014
Externally published	Yes

Keywords

Ag-126
Alphavirus
ERK
Extracellular signal-regulated kinase
Kinase
MAPK

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10.1016/j.virol.2014.09.005

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title = "Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells",

abstract = "New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated in Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses.",

keywords = "Ag-126, Alphavirus, ERK, Extracellular signal-regulated kinase, Kinase, MAPK",

author = "Kelsey Voss and Moushimi Amaya and Claudius Mueller and Brian Roberts and Kylene Kehn-Hall and Charles Bailey and Emanuel Petricoin and Aarthi Narayanan",

note = "Publisher Copyright: {\textcopyright} 2014.",

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doi = "10.1016/j.virol.2014.09.005",

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AU - Voss, Kelsey

AU - Amaya, Moushimi

AU - Mueller, Claudius

AU - Roberts, Brian

AU - Kehn-Hall, Kylene

AU - Bailey, Charles

AU - Petricoin, Emanuel

AU - Narayanan, Aarthi

PY - 2014/11/1

Y1 - 2014/11/1

N2 - New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated in Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses.

AB - New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated in Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses.

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KW - ERK

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KW - Kinase

KW - MAPK

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DO - 10.1016/j.virol.2014.09.005

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SN - 0042-6822

VL - 468

SP - 490

EP - 503

JO - Virology

JF - Virology

ER -

Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells

Abstract

Keywords

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