Transcriptome Analysis of Human Peripheral Blood Mononuclear Cells Exposed to Lassa Virus and to the Attenuated Mopeia/Lassa Reassortant 29 (ML29), a Vaccine Candidate.

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dc.contributorVirginia Techen
dc.contributor.authorZapata, Juan Carlosen
dc.contributor.authorCarrion, Ricardo Jr.en
dc.contributor.authorPatterson, Jean L.en
dc.contributor.authorCrasta, Oswalden
dc.contributor.authorZhang, Yanen
dc.contributor.authorMani, Sachinen
dc.contributor.authorJett, Martien
dc.contributor.authorPoonia, Bhawnaen
dc.contributor.authorDjavani, Mahmouden
dc.contributor.authorWhite, David M.en
dc.contributor.authorLukashevich, Igor S.en
dc.contributor.authorSalvato, Maria S.en
dc.date.accessed2014-04-09en
dc.date.accessioned2014-04-09T15:07:23Zen
dc.date.available2014-04-09T15:07:23Zen
dc.date.issued2013-09-12en
dc.description.abstractLassa virus (LASV) is the causative agent of Lassa Fever and is responsible for several hundred thousand infections and thousands of deaths annually in West Africa. LASV and the non-pathogenic Mopeia virus (MOPV) are both rodent-borne African arenaviruses. A live attenuated reassortant of MOPV and LASV, designated ML29, protects rodents and primates from LASV challenge and appears to be more attenuated than MOPV. To gain better insight into LASV-induced pathology and mechanism of attenuation we performed gene expression profiling in human peripheral blood mononuclear cells (PBMC) exposed to LASV and the vaccine candidate ML29. PBMC from healthy human subjects were exposed to either LASV or ML29. Although most PBMC are non-permissive for virus replication, they remain susceptible to signal transduction by virus particles. Total RNA was extracted and global gene expression was evaluated during the first 24 hours using highdensity microarrays. Results were validated using RT-PCR, flow cytometry and ELISA. LASV and ML29 elicited differential expression of interferon-stimulated genes (ISG), as well as genes involved in apoptosis, NF-kB signaling and the coagulation pathways. These genes could eventually serve as biomarkers to predict disease outcomes. The remarkable differential expression of thrombomodulin, a key regulator of inflammation and coagulation, suggests its involvement with vascular abnormalities and mortality in Lassa fever disease.en
dc.description.sponsorshipThis work was supported by funding from the National Institutes of Health and by the Regional Centers of Excellence in Biodefense and Emerging Infectious Diseases Research, MARCE (U54 AI057168, subcontracts to MSS and to ISL) and WRCE (U54 AI057156, subcontract to JLP and RC). Funding for microarray studies was from NIH grants AI053620 and AI053619 (to MSS). DC infections with LASV and ELISA conducted at the USCDC BSL-4 facilities by DMW were supported by the US-CDC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.identifier.citationZapata JC, Carrion R Jr, Patterson JL, Crasta O, Zhang Y, et al. (2013) Transcriptome Analysis of Human Peripheral Blood Mononuclear Cells Exposed to Lassa Virus and to the Attenuated Mopeia/Lassa Reassortant 29 (ML29), a Vaccine Candidate. PLoS Negl Trop Dis 7(9): e2406. doi:10.1371/journal.pntd.0002406en
dc.identifier.doihttps://doi.org/10.1371/journal.pntd.0002406en
dc.identifier.issn1935-2735en
dc.identifier.urihttp://hdl.handle.net/10919/47014en
dc.language.isoen_USen
dc.publisherPLoS Negl Troop Disen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectApoptosisen
dc.subjectExtracellular Matrix proteinsen
dc.subjectGene expressionen
dc.subjectImmune responseen
dc.subjectIntegrinsen
dc.subjectPlateletsen
dc.subjectTranscriptome analysiusen
dc.titleTranscriptome Analysis of Human Peripheral Blood Mononuclear Cells Exposed to Lassa Virus and to the Attenuated Mopeia/Lassa Reassortant 29 (ML29), a Vaccine Candidate.en
dc.title.serialPLoS Neglected Tropical Diseasesen
dc.typeArticle - Refereeden

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