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dc.contributor.authorMacManiman, JD
dc.contributor.authorMeuser, A
dc.contributor.authorBotto, S
dc.contributor.authorSmith, PP
dc.contributor.authorLiu, F
dc.contributor.authorJarvis, Michael A
dc.contributor.authorNelson, JA
dc.contributor.authorCaposio, P
dc.date.accessioned2015-07-17T08:00:01Z
dc.date.available2015-07-17T08:00:01Z
dc.date.issued2014-12-31
dc.identifier.issn2161-2129
dc.identifier.issn2150-7511
dc.identifier.otherARTN e02035-14
dc.identifier.urihttp://hdl.handle.net/10026.1/3437
dc.description.abstract

<jats:title>ABSTRACT</jats:title> <jats:p>Persistent human cytomegalovirus (HCMV) infection has been linked to several diseases, including atherosclerosis, transplant vascular sclerosis (TVS), restenosis, and glioblastoma. We have previously shown that factors secreted from HCMV-infected cells induce angiogenesis and that this process is due, at least in part, to increased secretion of interleukin-6 (IL-6). In order to identify the HCMV gene(s) responsible for angiogenesis promotion, we constructed a large panel of replication-competent HCMV recombinants. One HCMV recombinant deleted for UL1 to UL10 was unable to induce secretion of factors necessary for angiogenesis. Fine mapping using additional HCMV recombinants identified UL7 as a viral gene required for production of angiogenic factors from HCMV-infected cells. Transient expression of pUL7 induced phosphorylation of STAT3 and ERK1/2 MAP kinases and production of proangiogenic factors, including IL-6. Addition of recombinant pUL7 to cells was sufficient for angiogenesis and was again associated with increased IL-6 expression. Analysis of the UL7 structure revealed a conserved domain similar to the immunoglobulin superfamily domain and related to the N-terminal V-like domain of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Our report therefore identifies UL7 as a novel HCMV-encoded molecule that is both structurally and functionally related to cellular CEACAM1, a proangiogenic factor highly expressed during vasculogenesis.</jats:p> <jats:p> <jats:bold>IMPORTANCE</jats:bold> A hallmark of cytomegalovirus (CMV) infection is its ability to modulate the host cellular machinery, resulting in the secretion of factors associated with long-term diseases such as vascular disorders and cancer. We previously demonstrated that HCMV infection alters the types and quantities of bioactive proteins released from cells (designated the HCMV secretome) that are involved in the promotion of angiogenesis and wound healing. A key proangiogenic and antiapoptotic factor identified from a proteomic-based approach was IL-6. In the present report, we show for the first time that HCMV UL7 encodes a soluble molecule that is a structural and functional homologue of the CEACAM1 proangiogenic cellular factor. This report thereby identifies a critical component of the HCMV secretome that may be responsible, at least in part, for the vascular dysregulation associated with persistent HCMV infection. </jats:p>

dc.format.extente02035-
dc.format.mediumElectronic
dc.languageen
dc.language.isoeng
dc.publisherAmerican Society for Microbiology
dc.subjectAmino Acid Sequence
dc.subjectAntigens, CD
dc.subjectCell Adhesion Molecules
dc.subjectCytomegalovirus
dc.subjectHumans
dc.subjectInterleukin-6
dc.subjectMolecular Sequence Data
dc.subjectNeovascularization, Pathologic
dc.subjectProtein Conformation
dc.subjectProtein Structure, Tertiary
dc.subjectRecombination, Genetic
dc.subjectSequence Alignment
dc.subjectViral Matrix Proteins
dc.subjectVirus Replication
dc.titleHuman Cytomegalovirus-Encoded pUL7 Is a Novel CEACAM1-Like Molecule Responsible for Promotion of Angiogenesis
dc.typejournal-article
dc.typeJournal Article
dc.typeResearch Support, N.I.H., Extramural
plymouth.author-urlhttps://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000347073600032&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008
plymouth.issue6
plymouth.volume5
plymouth.publication-statusPublished
plymouth.journalmBio
dc.identifier.doi10.1128/mbio.02035-14
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/School of Biomedical Sciences
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/Research Groups
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
dc.publisher.placeUnited States
dc.identifier.eissn2150-7511
dc.rights.embargoperiodNot known
rioxxterms.versionofrecord10.1128/mbio.02035-14
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review


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