2024
Persistent SARS-CoV-2 infection: significance and implications
Machkovech H, Hahn A, Garonzik Wang J, Grubaugh N, Halfmann P, Johnson M, Lemieux J, O'Connor D, Piantadosi A, Wei W, Friedrich T. Persistent SARS-CoV-2 infection: significance and implications. The Lancet Infectious Diseases 2024, 24: e453-e462. PMID: 38340735, DOI: 10.1016/s1473-3099(23)00815-0.Peer-Reviewed Original ResearchPersistent SARS-CoV-2 infectionSARS-CoV-2 infectionSuboptimal immune responsesPre-existing immunityPersistent virus replicationMonitoring viral evolutionPublic health problemTissue reservoirsImmunocompromised individualsTreatment strategiesPersistent infectionPublic health priorityImmune responseSARS-CoV-2 replicationSARS-CoV-2Virus replicationInfectionVirus variantsViral evolutionHealth priorityHealth problemsTreatmentPathophysiologyPatientsDiagnosis
2023
Immunogenicity and Pre-Clinical Efficacy of an OMV-Based SARS-CoV-2 Vaccine
Grandi A, Tomasi M, Ullah I, Bertelli C, Vanzo T, Accordini S, Gagliardi A, Zanella I, Benedet M, Corbellari R, Di Lascio G, Tamburini S, Caproni E, Croia L, Ravà M, Fumagalli V, Di Lucia P, Marotta D, Sala E, Iannacone M, Kumar P, Mothes W, Uchil P, Cherepanov P, Bolognesi M, Pizzato M, Grandi G. Immunogenicity and Pre-Clinical Efficacy of an OMV-Based SARS-CoV-2 Vaccine. Vaccines 2023, 11: 1546. PMID: 37896949, PMCID: PMC10610814, DOI: 10.3390/vaccines11101546.Peer-Reviewed Original ResearchSARS-CoV-2 vaccinesSARS-CoV-2Outer membrane vesiclesImmune responseSARS-CoV-2 elicitsSARS-CoV-2 variantsPotent immune responsesEffective immune responsePre-clinical efficacyDiverse SARS-CoV-2 variantsInherent adjuvanticityVaccinated miceIntranasal challengeVaccine dosesNeutralization titresEffective vaccineVirus infectionVaccination campaignHeterologous antigensVaccineVirus replicationSpike proteinInfectivity assaysTitresPotential needCMPK2 restricts Zika virus replication by inhibiting viral translation
Pawlak J, Hsu J, Xia H, Han P, Suh H, Grove T, Morrison J, Shi P, Cresswell P, Laurent-Rolle M. CMPK2 restricts Zika virus replication by inhibiting viral translation. PLOS Pathogens 2023, 19: e1011286. PMID: 37075076, PMCID: PMC10150978, DOI: 10.1371/journal.ppat.1011286.Peer-Reviewed Original ResearchConceptsCytidine/uridine monophosphate kinase 2I interferon-stimulated genesZika virus replicationYellow fever virusAntiviral activityAntiviral effectVirus replicationKunjin virusType I interferon-stimulated genesFirst lineOverall antiviral responseHost's first lineEffective therapeutic interventionsViral translationBroad antiviral activityInterferon-stimulated genesGlobal health threatAntiviral treatmentFlaviviral infectionsPathogenic flavivirusesAntiviral functionDrug AdministrationTherapeutic interventionsAntiviral responseDengue virusRebound HIV-1 in cerebrospinal fluid after antiviral therapy interruption is mainly clonally amplified R5 T cell-tropic virus
Kincer L, Joseph S, Gilleece M, Hauser B, Sizemore S, Zhou S, Di Germanio C, Zetterberg H, Fuchs D, Deeks S, Spudich S, Gisslen M, Price R, Swanstrom R. Rebound HIV-1 in cerebrospinal fluid after antiviral therapy interruption is mainly clonally amplified R5 T cell-tropic virus. Nature Microbiology 2023, 8: 260-271. PMID: 36717718, PMCID: PMC10201410, DOI: 10.1038/s41564-022-01306-6.Peer-Reviewed Original ResearchConceptsCentral nervous systemT cell-tropic virusesInfected T cellsCerebrospinal fluidAntiretroviral therapyHIV-1Rebound virusViral loadT cellsMacrophage-tropic HIV-1CSF viral loadSuppressive antiretroviral therapyHIV-1 reservoirMacrophage-tropic virusesHigh viral loadWhite blood cellsTherapy interruptionLatent reservoirLymphoid systemNervous systemSystemic infectionVirus replicationBlood cellsTransient influxVirus
2021
Translational shutdown and evasion of the innate immune response by SARS-CoV-2 NSP14 protein
Hsu JC, Laurent-Rolle M, Pawlak JB, Wilen CB, Cresswell P. Translational shutdown and evasion of the innate immune response by SARS-CoV-2 NSP14 protein. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2101161118. PMID: 34045361, PMCID: PMC8214666, DOI: 10.1073/pnas.2101161118.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Interferon-stimulated genesImmune responseSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Host protein synthesisRespiratory syndrome coronavirus 2Syndrome coronavirus 2Innate immune responseUnprecedented global health crisisCoronavirus 2N7-methyltransferase activityOngoing COVID-19 pandemicHuman coronavirusesTranslational shutdownVirus replicationNsp14 proteinGlobal health crisisProtein synthesisInhibition activityCausative agentCOVID-19COVID-19 pandemicSARS-CoV-2 nsp14Dependent induction
2020
Convalescent plasma treatment of severe COVID-19: a propensity score–matched control study
Liu S, Lin H, Baine I, Wajnberg A, Gumprecht J, Rahman F, Rodriguez D, Tandon P, Bassily-Marcus A, Bander J, Sanky C, Dupper A, Zheng A, Nguyen F, Amanat F, Stadlbauer D, Altman D, Chen B, Krammer F, Mendu D, Firpo-Betancourt A, Levin M, Bagiella E, Casadevall A, Cordon-Cardo C, Jhang J, Arinsburg S, Reich D, Aberg J, Bouvier N. Convalescent plasma treatment of severe COVID-19: a propensity score–matched control study. Nature Medicine 2020, 26: 1708-1713. PMID: 32934372, DOI: 10.1038/s41591-020-1088-9.Peer-Reviewed Original ResearchConceptsPlasma recipientsSARS-CoV-2Convalescent plasmaLife-threatening COVID-19Suppress virus replicationConvalescent plasma therapyEffectiveness of convalescent plasma therapyScore-matched controlsVirus-specific antibodiesMount Sinai HospitalRandomized Controlled TrialsPlasma therapySevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Controlled studiesAcellular componentsControlled TrialsSyndrome coronavirus 2Sinai HospitalAntiviral effectPatientsOxygen requirementVirus replicationAntibodiesCell-penetrating peptide inhibits retromer-mediated human papillomavirus trafficking during virus entry
Zhang P, Moreno R, Lambert PF, DiMaio D. Cell-penetrating peptide inhibits retromer-mediated human papillomavirus trafficking during virus entry. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 6121-6128. PMID: 32123072, PMCID: PMC7084110, DOI: 10.1073/pnas.1917748117.Peer-Reviewed Original ResearchConceptsEssential protein-protein interactionsCellular protein complexesProtein-protein interactionsIntracellular virus traffickingRetrograde transport pathwaySites of replicationCell-penetrating sequenceProtein complexesCellular proteinsVirus replicationHPV16 pseudovirus infectionVirus traffickingL2 capsid proteinsAspects of infectionCapsid proteinHPV entryViral genomeViral proteinsIncoming virionsViral componentsHuman papillomavirus infectionProteinAntiviral targetDose-dependent blockVirus entry
2019
Influenza A virus M2 protein triggers mitochondrial DNA-mediated antiviral immune responses
Moriyama M, Koshiba T, Ichinohe T. Influenza A virus M2 protein triggers mitochondrial DNA-mediated antiviral immune responses. Nature Communications 2019, 10: 4624. PMID: 31604929, PMCID: PMC6789137, DOI: 10.1038/s41467-019-12632-5.Peer-Reviewed Original ResearchConceptsMitochondrial DNANonstructural protein 1Cytosolic mitochondrial DNAMtDNA releaseInfluenza virus M2Antiviral immune responseImportance of DNAVirus M2 proteinImmune responseViroporin activityMAVS-dependent mannerTriggers translocationVirus replicationCytosolic mtDNAAntiviral signalingVirus M2M2 proteinRNA virusesInnate immune responseMtDNAInfluenza virus replicationInfluenza virusNeighboring cellsProtein 1Gap junctionsInhibition of Chikungunya Virus Replication in Primary Human Fibroblasts by Liver X Receptor Agonist
Hwang J, Wang Y, Fikrig E. Inhibition of Chikungunya Virus Replication in Primary Human Fibroblasts by Liver X Receptor Agonist. Antimicrobial Agents And Chemotherapy 2019, 63: 10.1128/aac.01220-19. PMID: 31307983, PMCID: PMC6709483, DOI: 10.1128/aac.01220-19.Peer-Reviewed Original ResearchMeSH KeywordsAntiviral AgentsApolipoproteins EATP Binding Cassette Transporter 1ATP Binding Cassette Transporter, Subfamily G, Member 1Chikungunya virusCholesterolFibroblastsGene Expression RegulationHost-Pathogen InteractionsHumansIndazolesInterferonsLiver X ReceptorsPrimary Cell CultureRNA, Small InterferingSignal TransductionVirus ReplicationConceptsChikungunya virusLiver X receptor agonistMosquito-borne chikungunya virusX receptor agonistLiver X receptorChikungunya Virus ReplicationLXR-623Acute painJoint inflammationReceptor agonistCHIKV replicationPharmacological activationSynthetic agonistsAntiviral stateVirus replicationX receptorLarge epidemicsHost factorsAgonistsPrimary human fibroblastsVirusHuman fibroblastsPainInflammationGeographic areasMouse Norovirus Infection Arrests Host Cell Translation Uncoupled from the Stress Granule-PKR-eIF2α Axis
Fritzlar S, Aktepe TE, Chao YW, Kenney ND, McAllaster MR, Wilen CB, White PA, Mackenzie JM. Mouse Norovirus Infection Arrests Host Cell Translation Uncoupled from the Stress Granule-PKR-eIF2α Axis. MBio 2019, 10: 10.1128/mbio.00960-19. PMID: 31213553, PMCID: PMC6581855, DOI: 10.1128/mbio.00960-19.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaliciviridae InfectionsCytoplasmic GranulesDNA HelicaseseIF-2 KinaseEukaryotic Initiation Factor-2Host-Pathogen InteractionsImmune EvasionImmunity, InnateMicePhosphorylationPoly-ADP-Ribose Binding ProteinsProtein BiosynthesisRNA HelicasesRNA Recognition Motif ProteinsViral ProteinsVirus ReplicationConceptsIntegrated stress responseProtein kinase RStress granulesProtein translationCellular homeostasisProtein G3BP1Host translationCytoplasmic RNA granulesMNV replication complexHijack host machineryPhosphorylation of eIF2αHost protein translationCellular response systemsHost cell translationEukaryotic initiation factorMNV infectionPhosphorylated eukaryotic initiation factorRNA granulesTranslational controlSG formationInitiation factorsSG nucleationTranslational arrestHost machineryVirus replicationDistinct Requirements for HIV-1 Accessory Proteins during Cell Coculture and Cell-Free Infection
Zotova A, Atemasova A, Pichugin A, Filatov A, Mazurov D. Distinct Requirements for HIV-1 Accessory Proteins during Cell Coculture and Cell-Free Infection. Viruses 2019, 11: 390. PMID: 31027334, PMCID: PMC6563509, DOI: 10.3390/v11050390.Peer-Reviewed Original ResearchMeSH KeywordsCD4-Positive T-LymphocytesCell LineCell-Free SystemCells, CulturedCoculture TechniquesGene Expression Regulation, ViralGene Knockdown TechniquesHIV InfectionsHIV-1Human Immunodeficiency Virus ProteinsHumansJurkat CellsMutationnef Gene Products, Human Immunodeficiency VirusViral Regulatory and Accessory ProteinsVirus ReplicationConceptsCell-free infectionHIV-1 infectionCell coculturesHIV-1Cell-to-cell transmission of HIV-1Transmission of HIV-1Nonlymphoid cellsHIV-1 accessory proteinHIV-1 replicationMeasuring virus replicationVirus replicationCell-to-cell transmissionEffector cellsLymphoid cellsMode of transmissionTarget cellsProducing cellsStages of infectionEnhanced replicationAccessory proteinsInfectionCocultureInfected cellsReporter vectorViral particles
2018
Rev-erb Agonist Inhibits Chikungunya and O’nyong’nyong Virus Replication
Hwang J, Jiang A, Fikrig E. Rev-erb Agonist Inhibits Chikungunya and O’nyong’nyong Virus Replication. Open Forum Infectious Diseases 2018, 5: ofy315. PMID: 30568983, PMCID: PMC6293476, DOI: 10.1093/ofid/ofy315.Peer-Reviewed Original ResearchChikungunya virusSubset of patientsRecent global epidemicJoint painStructural protein synthesisSevere inflammationInflammatory responseMultiple alphavirusesViral RNA accumulationGlobal epidemicSynthetic agonistsVirus replicationCultured murine macrophagesMurine macrophagesSR9009AlphavirusesRelated virusesVirusProtein synthesisPainInflammationPatientsAgonistsMacrophagesRNA accumulationInterferon-stimulated TRIM69 interrupts dengue virus replication by ubiquitinating viral nonstructural protein 3
Wang K, Zou C, Wang X, Huang C, Feng T, Pan W, Wu Q, Wang P, Dai J. Interferon-stimulated TRIM69 interrupts dengue virus replication by ubiquitinating viral nonstructural protein 3. PLOS Pathogens 2018, 14: e1007287. PMID: 30142214, PMCID: PMC6126873, DOI: 10.1371/journal.ppat.1007287.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsAnimalsAnophelesCells, CulturedDengue VirusGene Expression RegulationHEK293 CellsHeLa CellsHuman Umbilical Vein Endothelial CellsHumansInterferon Type IMiceProtein Processing, Post-TranslationalRNA HelicasesSerine EndopeptidasesTripartite Motif ProteinsUbiquitin-Protein LigasesUbiquitinationUp-RegulationViral Nonstructural ProteinsVirus ReplicationConceptsInterferon-stimulated genesI interferonNonstructural protein 3DENV replicationMost interferon-stimulated genesProtein 3Dengue virus infectionDengue virus replicationType I interferonViral nonstructural protein 3DENV infectionImmunocompetent miceVirus infectionViral infectionAntiviral activityVirus replicationVivo studiesInfectionTripartite motif (TRIM) proteinsTRIM family membersViral nonstructural proteinsFamily membersNonstructural proteinsTRIM69E3 ubiquitin ligase activityAn Antiviral Branch of the IL-1 Signaling Pathway Restricts Immune-Evasive Virus Replication
Orzalli MH, Smith A, Jurado KA, Iwasaki A, Garlick JA, Kagan JC. An Antiviral Branch of the IL-1 Signaling Pathway Restricts Immune-Evasive Virus Replication. Molecular Cell 2018, 71: 825-840.e6. PMID: 30100266, PMCID: PMC6411291, DOI: 10.1016/j.molcel.2018.07.009.Peer-Reviewed Original ResearchConceptsDamage-associated molecular patternsIL-1Host-derived damage-associated molecular patternsViral replicationVirus replicationInfected cellsInterleukin-1 family cytokinesIL-1 Signaling PathwayInflammatory gene expressionIL-1 actsHuman skin explantsProtective immunityIL-1αBarrier defenseInflammatory signalsViral infectionFamily cytokinesSkin explantsGene expressionMolecular patternsSkin fibroblastsSignaling pathwaysAntiviral systemBarrier epitheliaCell typesSmall Interfering RNA-Mediated Control of Virus Replication in the CNS Is Therapeutic and Enables Natural Immunity to West Nile Virus
Beloor J, Maes N, Ullah I, Uchil P, Jackson A, Fikrig E, Lee SK, Kumar P. Small Interfering RNA-Mediated Control of Virus Replication in the CNS Is Therapeutic and Enables Natural Immunity to West Nile Virus. Cell Host & Microbe 2018, 23: 549-556.e3. PMID: 29606496, PMCID: PMC6074029, DOI: 10.1016/j.chom.2018.03.001.Peer-Reviewed Original ResearchConceptsWest Nile virusWNV infectionCell-mediated immune responsesLate-stage therapySubsequent WNV infectionWNV-infected miceLong-term immunityNile virusWNV E proteinViral burdenIntranasal routeVirus clearanceVirus infectionImmune responseMice succumbPeripheral tissuesNatural immunitySurvival rateDisease resultsDay 9Virus replicationInfectionImmunityCNSVirus
2017
Tylophorine Analogs Allosterically Regulates Heat Shock Cognate Protein 70 And Inhibits Hepatitis C Virus Replication
Wang Y, Lee S, Ha Y, Lam W, Chen SR, Dutschman GE, Gullen EA, Grill SP, Cheng Y, Fürstner A, Francis S, Baker DC, Yang X, Lee KH, Cheng YC. Tylophorine Analogs Allosterically Regulates Heat Shock Cognate Protein 70 And Inhibits Hepatitis C Virus Replication. Scientific Reports 2017, 7: 10037. PMID: 28855547, PMCID: PMC5577180, DOI: 10.1038/s41598-017-08815-z.Peer-Reviewed Original ResearchConceptsHepatitis C virus replicationC virus replicationTylophorine analogsHCV replicationHeat shock cognate protein 70HCV RNAShock cognate protein 70Inhibits Hepatitis C Virus ReplicationVirus replicationProtein 70Anti-HCV activityHCV replication complexPotent inhibitory activityExhibit potent inhibitory activityInhibitory activityATPase activityArthritisInflammationLupusReplicationActivityCancerHsc70Zika virus causes testicular atrophy
Uraki R, Hwang J, Jurado KA, Householder S, Yockey LJ, Hastings AK, Homer RJ, Iwasaki A, Fikrig E. Zika virus causes testicular atrophy. Science Advances 2017, 3: e1602899. PMID: 28261663, PMCID: PMC5321463, DOI: 10.1126/sciadv.1602899.Peer-Reviewed Original ResearchConceptsZika virusTesticular atrophyAcute viremic phaseZIKV-infected miceMosquito-borne flavivirusTestosterone-producing Leydig cellsProgressive testicular atrophyZIKV persistenceFetal infectionViremic phaseNeonatal abnormalitiesSerum testosteroneZIKV infectionNeurological dysfunctionSubcutaneous injectionZIKV replicationLeydig cellsVirus replicationVertical transmissionEpithelial cellsMiceViral RNAReproductive deficienciesAtrophyMale fertility
2016
Pharmacodynamics of anti-HIV gene therapy using viral vectors and targeted endonucleases
Roychoudhury P, De Silva Feelixge H, Pietz H, Stone D, Jerome K, Schiffer J. Pharmacodynamics of anti-HIV gene therapy using viral vectors and targeted endonucleases. Journal Of Antimicrobial Chemotherapy 2016, 71: 2089-2099. PMID: 27090632, PMCID: PMC4954920, DOI: 10.1093/jac/dkw104.Peer-Reviewed Original ResearchConceptsVector serotypeViral vectorsDose selectionAnti-HIV gene therapyHIV-infected cellsEngineered viral vectorsGene therapy applicationsDose-response relationshipFunctional cureGene expressionGene therapyReporter geneSigmoid dose-response relationshipTransduction efficiencyCurative approachViral uptakeTherapeutic outcomesTarget cellsIndividual target cellsDoseExpress transgenesVirus replicationTherapy applicationsLatent genomesActivation of endonucleases
2014
Hepatitis C virus genetics affects miR-122 requirements and response to miR-122 inhibitors
Israelow B, Mullokandov G, Agudo J, Sourisseau M, Bashir A, Maldonado AY, Dar AC, Brown BD, Evans MJ. Hepatitis C virus genetics affects miR-122 requirements and response to miR-122 inhibitors. Nature Communications 2014, 5: 5408. PMID: 25403145, PMCID: PMC4236719, DOI: 10.1038/ncomms6408.Peer-Reviewed Original ResearchConceptsMiR-122Hepatitis C virus replicationRecent clinical trialsC virus replicationMiR-122 inhibitionMiR-122 inhibitorClinical trialsHCV replicationMiR-122 knockdownHCV drugsHCV variantsHCVHCV genomeViral titresVirus replicationNext-generation sequencingTransient inhibitionVirus geneticsViral adaptationViral sequencesInhibitionNucleotide changesSingle nucleotide changePatientsTitres
2013
An Example of Genetically Distinct HIV Type 1 Variants in Cerebrospinal Fluid and Plasma During Suppressive Therapy
Dahl V, Gisslen M, Hagberg L, Peterson J, Shao W, Spudich S, Price RW, Palmer S. An Example of Genetically Distinct HIV Type 1 Variants in Cerebrospinal Fluid and Plasma During Suppressive Therapy. The Journal Of Infectious Diseases 2013, 209: 1618-1622. PMID: 24338353, PMCID: PMC3997583, DOI: 10.1093/infdis/jit805.Peer-Reviewed Original ResearchConceptsCentral nervous systemSuppressive therapyTreatment initiationNervous systemPlasma sequencesHIV Type 1 VariantsHuman immunodeficiency virus type 1Immunodeficiency virus type 1Cerebrospinal fluid specimensType 1 variantsVirus type 1CSF sequencesViral persistenceHIV-1Cerebrospinal fluidFluid specimensTherapyType 1Virus replicationMajor causePlasma samplesCSFViral evolutionSubjectsLittle evidence
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