2023
HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing
Lyons D, Kumar P, Roan N, Defechereux P, Feschotte C, Lange U, Murthy N, Sameshima P, Verdin E, Ake J, Parsons M, Nath A, Gianella S, Smith D, Kallas E, Villa T, Strange R, Mwesigwa B, O’Brien R, Nixon D, Ndhlovu L, Valente S, Ott M. HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing. Viruses 2023, 15: 2171. PMID: 38005849, PMCID: PMC10674359, DOI: 10.3390/v15112171.Peer-Reviewed Original Research
2022
Engineered ACE2-Fc counters murine lethal SARS-CoV-2 infection through direct neutralization and Fc-effector activities
Chen Y, Sun L, Ullah I, Beaudoin-Bussières G, Anand SP, Hederman AP, Tolbert WD, Sherburn R, Nguyen DN, Marchitto L, Ding S, Wu D, Luo Y, Gottumukkala S, Moran S, Kumar P, Piszczek G, Mothes W, Ackerman ME, Finzi A, Uchil PD, Gonzalez FJ, Pazgier M. Engineered ACE2-Fc counters murine lethal SARS-CoV-2 infection through direct neutralization and Fc-effector activities. Science Advances 2022, 8: eabn4188. PMID: 35857504, PMCID: PMC9278865, DOI: 10.1126/sciadv.abn4188.Peer-Reviewed Original ResearchAngiotensin-converting enzyme 2Soluble angiotensin-converting enzyme 2Fc effector functionsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptorLethal SARS-CoV-2 infectionK18-hACE2 mouse modelSARS-CoV-2 infectionAntibody-dependent cellular cytotoxicitySARS-CoV-2 antiviralsFc effector activityCoV-2 infectionSARS-CoV-2 variantsHalf maximal inhibitory concentrationComplement depositionACE2-FcCellular cytotoxicityEnzyme 2Mouse modelTherapeutic activityInhibitory concentrationTherapeutic settingDirect neutralizationInfectionReceptorsEffect of neutralizationVE607 stabilizes SARS-CoV-2 Spike in the “RBD-up” conformation and inhibits viral entry
Ding S, Ullah I, Gong SY, Grover J, Mohammadi M, Chen Y, Vézina D, Beaudoin-Bussières G, Verma VT, Goyette G, Gaudette F, Richard J, Yang D, Smith AB, Pazgier M, Côté M, Abrams C, Kumar P, Mothes W, Uchil P, Finzi A, Baron C. VE607 stabilizes SARS-CoV-2 Spike in the “RBD-up” conformation and inhibits viral entry. IScience 2022, 25: 104528. PMID: 35677392, PMCID: PMC9164512, DOI: 10.1016/j.isci.2022.104528.Peer-Reviewed Original ResearchSARS-CoV-2 infectionAuthentic SARS-CoV-2K18-hACE2 miceS-ACE2 interactionsDevelopment of immunotherapySARS-CoV-2 spikeSARS-CoV-2SARS-CoV-1Prophylactic treatmentLow micromolar concentrationsViral replicationACE2 receptorPseudoviral particlesViral entrySpike glycoproteinPotential targetCOVID-19Drug developmentInfectionACE2 interfaceHost cellsMicromolar concentrationsReceptorsTreatmentRBDA Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection
Beaudoin-Bussières G, Chen Y, Ullah I, Prévost J, Tolbert WD, Symmes K, Ding S, Benlarbi M, Gong SY, Tauzin A, Gasser R, Chatterjee D, Vézina D, Goyette G, Richard J, Zhou F, Stamatatos L, McGuire AT, Charest H, Roger M, Pozharski E, Kumar P, Mothes W, Uchil PD, Pazgier M, Finzi A. A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection. Cell Reports 2022, 38: 110368. PMID: 35123652, PMCID: PMC8786652, DOI: 10.1016/j.celrep.2022.110368.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeutralizingAntibodies, ViralAntibody-Dependent Cell CytotoxicityCOVID-19COVID-19 SerotherapyDisease Models, AnimalEpitopesHumansImmunization, PassiveImmunoglobulin Fab FragmentsImmunoglobulin Fc FragmentsMiceProtein BindingProtein ConformationSARS-CoV-2Spike Glycoprotein, Coronavirus
2021
Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy
Ullah I, Prévost J, Ladinsky MS, Stone H, Lu M, Anand SP, Beaudoin-Bussières G, Symmes K, Benlarbi M, Ding S, Gasser R, Fink C, Chen Y, Tauzin A, Goyette G, Bourassa C, Medjahed H, Mack M, Chung K, Wilen CB, Dekaban GA, Dikeakos JD, Bruce EA, Kaufmann DE, Stamatatos L, McGuire AT, Richard J, Pazgier M, Bjorkman PJ, Mothes W, Finzi A, Kumar P, Uchil PD. Live imaging of SARS-CoV-2 infection in mice reveals that neutralizing antibodies require Fc function for optimal efficacy. Immunity 2021, 54: 2143-2158.e15. PMID: 34453881, PMCID: PMC8372518, DOI: 10.1016/j.immuni.2021.08.015.Peer-Reviewed Original ResearchConceptsCOVID-19 convalescent subjectsSARS-CoV-2 infectionBioluminescence imagingK18-hACE2 miceLive bioluminescence imagingNatural killer cellsFc effector functionsSARS-CoV-2Convalescent subjectsKiller cellsPotent NAbsImmune protectionInflammatory responseEffector functionsNasal cavityNaB treatmentOptimal efficacyFc functionDepletion studiesMiceNAbsCOVID-19Direct neutralizationInfectionAntibodiesLong‐acting and extended‐release implant and nanoformulations with a synergistic antiretroviral two‐drug combination controls HIV‐1 infection in a humanized mouse model
Beloor J, Kudalkar SN, Buzzelli G, Yang F, Mandl HK, Rajashekar JK, Spasov KA, Jorgensen WL, Saltzman WM, Anderson KS, Kumar P. Long‐acting and extended‐release implant and nanoformulations with a synergistic antiretroviral two‐drug combination controls HIV‐1 infection in a humanized mouse model. Bioengineering & Translational Medicine 2021, 7: e10237. PMID: 35079625, PMCID: PMC8780078, DOI: 10.1002/btm2.10237.Peer-Reviewed Original ResearchNucleoside reverse transcriptase inhibitorHIV-1 infectionAntiretroviral therapyHIV-1-infected humanized miceTwo-drug combinationsHumanized mouse modelLong-term treatmentReverse transcriptase inhibitorMaintenance of CD4Nonnucleoside reverseHumanized miceAntiretroviral formulationsAdherence issuesARV combinationsTranscriptase inhibitorHIV pandemicT cellsMouse modelInjectable nanoformulationsTherapeutic indexNew drugsSustained levelsInfectionDrugsInterventionNovel RNA Interference (RNAi)-Based Nanomedicines for Treating Viral Infections
Maes N, Zeller S, Kumar P. Novel RNA Interference (RNAi)-Based Nanomedicines for Treating Viral Infections. 2021, 223-264. DOI: 10.1201/9781003125259-8.Peer-Reviewed Original ResearchJapanese encephalitis virusNon-target tissuesHuman papillomavirusPediatric encephalitisTherapeutic modalitiesMajor safety concernNovel RNA interferenceViral infectionReplication-competent lentivirusClinical testingEncephalitis virusInfectious diseasesMajor causeSafety concernsDiseaseVector mobilizationRibonucleic acid interferenceTarget effectsRNA interferenceTargets of microRNAsEncephalitisPapillomavirusVaccineInfectionFlaviviruses
2019
Longitudinal bioluminescent imaging of HIV-1 infection during antiretroviral therapy and treatment interruption in humanized mice
Ventura JD, Beloor J, Allen E, Zhang T, Haugh KA, Uchil PD, Ochsenbauer C, Kieffer C, Kumar P, Hope TJ, Mothes W. Longitudinal bioluminescent imaging of HIV-1 infection during antiretroviral therapy and treatment interruption in humanized mice. PLOS Pathogens 2019, 15: e1008161. PMID: 31805155, PMCID: PMC6917343, DOI: 10.1371/journal.ppat.1008161.Peer-Reviewed Original ResearchConceptsHIV-1 infectionHumanized miceCombination antiretroviral therapy regimenViral spreadHIV-1 infection dynamicsNon-invasive bioluminescentAntiretroviral therapy regimenHIV-1 reporterSame lymphoid tissuesInfected cell populationCART withdrawalInfection recrudescenceAntiretroviral therapyTreatment interruptionTherapy regimenLymphoid tissueInfection dynamicsART treatmentBioluminescent imagingInfectionViral infection dynamicsInfected cellsCell populationsMiceBioluminescent signal
2018
Small 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
2015
Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection
Sewald X, Ladinsky MS, Uchil PD, Beloor J, Pi R, Herrmann C, Motamedi N, Murooka TT, Brehm MA, Greiner DL, Shultz LD, Mempel TR, Bjorkman PJ, Kumar P, Mothes W. Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection. Science 2015, 350: 563-567. PMID: 26429886, PMCID: PMC4651917, DOI: 10.1126/science.aab2749.Peer-Reviewed Original ResearchConceptsHuman immunodeficiency virusLymph nodesMurine leukemia virusCD169/SiglecSecondary lymphoid tissuesPermissive lymphocytesDendritic cellsImmunodeficiency virusSynaptic contactsLymphoid tissueRobust infectionVirological synapsesI-type lectinsRetroviral spreadViral spreadUninfected cellsInfectionLeukemia virusVirusMacrophagesCellsRetrovirusesCell-cell contactCD169Lymphocytes
2003
Screening for T cell-eliciting proteins of Japanese encephalitis virus in a healthy JE-endemic human cohort using recombinant baculovirus-infected insect cell preparations
Kumar P, Uchil PD, Sulochana P, Nirmala G, Chandrashekar R, Haridattatreya M, Satchidanandam V. Screening for T cell-eliciting proteins of Japanese encephalitis virus in a healthy JE-endemic human cohort using recombinant baculovirus-infected insect cell preparations. Archives Of Virology 2003, 148: 1569-1591. PMID: 12898332, DOI: 10.1007/s00705-003-0118-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, ViralBaculoviridaeCells, CulturedCohort StudiesEncephalitis Virus, JapaneseEncephalitis, JapaneseEndemic DiseasesFemaleHumansImmunologic MemoryLymphocyte ActivationMaleRecombinant ProteinsRNA HelicasesSerine EndopeptidasesSpodopteraT-LymphocytesViral Nonstructural ProteinsViral ProteinsConceptsJapanese encephalitis virusCell-mediated immune responsesT cell responsesImmune responseJEV infectionT cellsCell responsesEncephalitis virusAdaptive T cell responsesHuman cohortsTh1 immune responseMemory T cellsCell preparationsImmune controlHealthy individualsCohortWhole cell preparationsViral proteinsInfectionNS3 proteinImportant targetVirusCritical determinantNS1NS5 protein