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The Role of IKKβ in Venezuelan Equine Encephalitis Virus Infection

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dc.contributor.author Amaya, Moushimi
dc.contributor.author Voss, Kelsey
dc.contributor.author Sampey, Gavin
dc.contributor.author Senina, Svetlana
dc.contributor.author de la Fuente, Cynthia
dc.contributor.author Mueller, Claudius
dc.contributor.author Calvert, Valerie
dc.contributor.author Kehn-Hall, Kylene
dc.contributor.author Carpenter, Calvin
dc.contributor.author Kashanchi, Fatah
dc.contributor.author Bailey, Charles
dc.contributor.author Mogelsvang, Soren
dc.contributor.author Petricoin, Emanuel
dc.contributor.author Narayanan, Aarthi
dc.date.accessioned 2015-10-15T15:13:11Z
dc.date.available 2015-10-15T15:13:11Z
dc.date.issued 2014-02-19
dc.identifier.citation Amaya M, Voss K, Sampey G, Senina S, de la Fuente C, Mueller C, et al. (2014) The Role of IKKβ in Venezuelan Equine Encephalitis Virus Infection. PLoS ONE 9(2): e86745. doi:10.1371/journal.pone.0086745 en_US
dc.identifier.uri https://hdl.handle.net/1920/9946
dc.description.abstract Venezuelan equine encephalitis virus (VEEV) belongs to the genus Alphavirus, family Togaviridae. VEEV infection is characterized by extensive inflammation and studies from other laboratories implicated an involvement of the NF-κB cascade in the in vivo pathology. Initial studies indicated that at early time points of VEEV infection, the NF-κB complex was activated in cells infected with the TC-83 strain of VEEV. One upstream kinase that contributes to the phosphorylation of p65 is the IKKβ component of the IKK complex. Our previous studies with Rift valley fever virus, which exhibited early activation of the NF-κB cascade in infected cells, had indicated that the IKKβ component underwent macromolecular reorganization to form a novel low molecular weight form unique to infected cells. This prompted us to investigate if the IKK complex undergoes a comparable macromolecular reorganization in VEEV infection. Size-fractionated VEEV infected cell extracts indicated a macromolecular reorganization of IKKβ in VEEV infected cells that resulted in formation of lower molecular weight complexes. Well-documented inhibitors of IKKβ function, BAY-11-7082, BAY-11-7085 and IKK2 compound IV, were employed to determine whether IKKβ function was required for the production of infectious progeny virus. A decrease in infectious viral particles and viral RNA copies was observed with inhibitor treatment in the attenuated and virulent strains of VEEV infection. In order to further validate the requirement of IKKβ for VEEV replication, we over-expressed IKKβ in cells and observed an increase in viral titers. In contrast, studies carried out using IKKβ−/− cells demonstrated a decrease in VEEV replication. In vivo studies demonstrated that inhibitor treatment of TC-83 infected mice increased their survival. Finally, proteomics studies have revealed that IKKβ may interact with the viral protein nsP3. In conclusion, our studies have revealed that the host IKKβ protein may be critically involved in VEEV replication.
dc.description.sponsorship This work was supported by George Mason University start-up funds to AN, the US Department of Energy grant (DE- SC0001599) to CB and FK, and the generous support of the College of Science to the Center for Applied Proteomics and Molecular Medicine. Publication of this article was funded in part by the George Mason University Libraries Open Access Publishing Fund. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.rights Attribution 3.0 United States *
dc.rights.uri http://creativecommons.org/licenses/by/3.0/us/ *
dc.subject viral replication en_US
dc.subject phosphorylation en_US
dc.subject viral diseases en_US
dc.subject transfection en_US
dc.subject biotechnology en_US
dc.subject alphaviruses en_US
dc.subject neurons en_US
dc.subject host-pathogen interactions en_US
dc.title The Role of IKKβ in Venezuelan Equine Encephalitis Virus Infection en_US
dc.type Article en_US
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0086745


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