grant

Tegument Envelope Protein Interactions in CMV Envelopment

Organization UNIVERSITY OF ALABAMA AT BIRMINGHAMLocation BIRMINGHAM, UNITED STATESPosted 8 Nov 2022Deadline 31 Oct 2027
NIHUS FederalResearch GrantFY20250-11 years oldAcuteAnti-viral TherapyBiochemistryBiological ChemistryCMVCMV infectionCapsidCell BodyCell membraneCellsCellular MembraneChildChild YouthChildren (0-21)ComplexCryo-electron MicroscopyCryoelectron MicroscopyCytomegalic Inclusion DiseaseCytomegalovirusCytomegalovirus InfectionsCytoplasmCytoplasmic MembraneDNA mutationDataDose LimitingElectron CryomicroscopyEndosomesEnsureEnvelope ProteinGenerationsGenetic ChangeGenetic defectGenetic mutationGlycoproteinsGoalsGolgiGolgi ApparatusGolgi ComplexHCMVHerpesviridaeHerpesvirusesHumanImageImmunocompromisedImmunocompromised HostImmunocompromised PatientImmunosuppressed HostInclusion DiseaseIndividualInfantLicensingLipidsMTOCMalignantMalignant - descriptorMembraneMembrane Protein TrafficMembrane TrafficMetabolicMicro-tubuleMicrotubule-Organizing CenterMicrotubulesModern ManModificationMorbidityMorbidity - disease rateMorphogenesisMutationPathway interactionsPhenotypePlasma MembranePost-Translational Modification Protein/Amino Acid BiochemistryPost-Translational ModificationsPost-Translational Protein ModificationPost-Translational Protein ProcessingPosttranslational ModificationsPosttranslational Protein ProcessingProductionProtein ModificationProtein TraffickingProteinsReceptosomesRecyclingReportingRoleSalivary Gland Virus DiseaseSalivary Gland VirusesSiteStressStructural ProteinStructureTestingTherapeutic AgentsToxic effectToxicitiesVaccinesVacuoleViralViral DiseasesViral Gene ProductsViral Gene ProteinsViral ProteinsVirionVirusVirus AssemblyVirus DiseasesVirus ParticleVirus Replicationanti-viral developmentanti-viral drug developmentanti-viral therapeutic developmentanti-viral therapy developmentantiviral developmentantiviral drug developmentantiviral therapeutic developmentantiviral therapy developmentcryo-EMcryoEMcryogenic electron microscopycytomegalovirus groupdeveloping anti-viral agentdeveloping anti-viral drugdeveloping anti-viral therapeuticdeveloping anti-viral therapydeveloping antiviral agentdeveloping antiviral drugdeveloping antiviral therapeuticdeveloping antiviral therapyenv Antigensenv Gene Productsenv Polyproteinsenv Proteingenome mutationherpes virusimagingimmunosuppressed patientin uterointerestkidsmembrane structuremorphogenetic processmortalitymutantnovelparticlepathwayplasmalemmaprotein protein interactionprotein transportrecombinant virusresponsesocial rolestoichiometrytherapeutic agent developmenttherapeutic developmenttraffickingtrans-Golgi Networkvaccine strategyviral assemblyviral infectionviral infectious disease treatmentviral multiplicationviral replicationvirus infectionvirus multiplicationvirus proteinvirus-induced diseaseyoungster
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Full Description

Human cytomegalovirus (HCMV) is responsible for significant mortality and morbidity in immunocompromised patients and results in neurodevelopmental abnormalities in infants and children infected in-utero. Currently there is no licensed vaccine and antiviral therapies have dose limiting toxicities. Thus, further understanding of the replication of this virus, including mechanisms of virion envelopment, could identify new strategies for vaccine and antiviral drug development. In this proposal, we will define interactions between an essential virion glycoprotein complex, gM/gN, and membrane associated outer tegument proteins that lead to envelopment of the virus in a specialized cellular compartment, the assembly compartment.

Recombinant viruses with specific mutations in envelope and outer tegument proteins that result in shared phenotypes of defective envelopment will be used to define of viral glycoprotein/ tegument protein interactions required for virion assembly. In addition to increasing current understanding of herpesvirus assembly, results from these studies could potentially identify novel targets for development of therapeutics to limit replication of this virus.

Grant Number: 5R01AI173778-03
NIH Institute/Center: NIH

Principal Investigator: William Britt

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