Mason Archival Repository Service

Multi-Faceted Proteomic Characterization of Host Protein Complement of Rift Valley Fever Virus Virions and Identification of Specific Heat Shock Proteins, Including HSP90, as Important Viral Host Factors

Show simple item record

dc.contributor.author Nuss, Jonathan E.
dc.contributor.author Kehn-Hall, Kylene
dc.contributor.author Benedict, Ashwini
dc.contributor.author Costantino, Julie
dc.contributor.author Ward, Michael
dc.contributor.author Peyser, Brian D.
dc.contributor.author Retterer, Cary J.
dc.contributor.author Tressler, Lyal E.
dc.contributor.author Wanner, Laura M.
dc.contributor.author McGovern, Hugh F.
dc.contributor.author Zaidi, Anum
dc.contributor.author Anthony, Scott M.
dc.contributor.author Kota, Krishna P.
dc.contributor.author Bavari, Sina
dc.contributor.author Hakami, Ramin M.
dc.date.accessioned 2015-10-13T18:55:39Z
dc.date.available 2015-10-13T18:55:39Z
dc.date.issued 2014-05-08
dc.identifier.citation Nuss JE, Kehn-Hall K, Benedict A, Costantino J, Ward M, Peyser BD, et al. (2014) Multi-Faceted Proteomic Characterization of Host Protein Complement of Rift Valley Fever Virus Virions and Identification of Specific Heat Shock Proteins, Including HSP90, as Important Viral Host Factors. PLoS ONE 9(5): e93483. doi:10.1371/journal.pone.0093483 en_US
dc.identifier.uri https://hdl.handle.net/1920/9943
dc.description.abstract Rift Valley fever is a potentially fatal disease of humans and domestic animals caused by Rift Valley fever virus (RVFV). Infection with RVFV in ruminants can cause near 100% abortion rates and recent outbreaks in naïve human populations have suggested case fatality rates of greater than thirty percent. To elucidate the roles that host proteins play during RVFV infection, proteomic analysis of RVFV virions was conducted using complementary analytical approaches, followed by functional validation studies of select identified host factors. Coupling the more traditional Gel LC/MS/MS approach (SDS PAGE followed by liquid chromatography tandem mass spectrometry) with an alternative technique that preserves protein complexes allowed the protein complement of these viral particles to be thoroughly examined. In addition to viral proteins present within the virions and virion-associated host proteins, multiple macromolecular complexes were identified. Bioinformatic analysis showed that host chaperones were among over-represented protein families associated with virions, and functional experiments using siRNA gene silencing and small molecule inhibitors identified several of these heat shock proteins, including heat shock protein 90 (HSP90), as important viral host factors. Further analysis indicated that HSP inhibition effects occur during the replication/transcription phase of the virus life cycle, leading to significant lowering of viral titers without compromising the functional capacity of released virions. Overall, these studies provide much needed further insight into interactions between RVFV and host cells, increasing our understanding of the infection process and suggesting novel strategies for anti-viral development. In particular, considering that several HSP90 inhibitors have been advancing through clinical trials for cancer treatment, these results also highlight the exciting potential of repurposing HSP90 inhibitors to treat RVF.
dc.description.sponsorship This research was supported by funding awarded to R.M.H. by the U.S. Army Medical Research and Materiel Command (MRMC) (W81XWH-11-P-0310) and George Mason University, and by a grant awarded to S.B. from the Defense Threat Reduction Agency Transformational Medical Technologies [TMTI0048_09_RD_T]. 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 Rift Valley fever virus en_US
dc.subject small interfering RNAs en_US
dc.subject virions en_US
dc.subject heat shock response en_US
dc.subject chaperone proteins en_US
dc.subject membrane proteins en_US
dc.subject protein interaction networks en_US
dc.subject database searching en_US
dc.title Multi-Faceted Proteomic Characterization of Host Protein Complement of Rift Valley Fever Virus Virions and Identification of Specific Heat Shock Proteins, Including HSP90, as Important Viral Host Factors en_US
dc.type Article en_US
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0093483


Files in this item

The following license files are associated with this item:

This item appears in the following Collection(s)

Show simple item record

Attribution 3.0 United States Except where otherwise noted, this item's license is described as Attribution 3.0 United States

Search MARS


Browse

My Account

Statistics