2023
The KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses by mediating viral receptor expression
Wei J, Alfajaro M, Cai W, Graziano V, Strine M, Filler R, Biering S, Sarnik S, Patel S, Menasche B, Compton S, Konermann S, Hsu P, Orchard R, Yan Q, Wilen C. The KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses by mediating viral receptor expression. PLOS Pathogens 2023, 19: e1011351. PMID: 37410700, PMCID: PMC10325096, DOI: 10.1371/journal.ppat.1011351.Peer-Reviewed Original ResearchConceptsMouse hepatitis virusReceptor expressionTherapeutic targetMERS-CoVMajor SARS-CoV-2 variantsPrimary human airwaySARS-CoV-2 variantsNovel therapeutic targetViral receptor expressionSARS-CoV-2Histone methyltransferase KMT2DIntestinal epithelial cellsCoronavirus SusceptibilityDiverse coronavirusesHistone demethylase KDM6ADPP4 expressionCoronavirus receptorsHost determinantsHepatitis virusHuman airwaysSARS-CoVSmall molecule inhibitionViral entryPotential drug targetsViral receptorsPharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection
Wei J, Patil A, Collings C, Alfajaro M, Liang Y, Cai W, Strine M, Filler R, DeWeirdt P, Hanna R, Menasche B, Ökten A, Peña-Hernández M, Klein J, McNamara A, Rosales R, McGovern B, Luis Rodriguez M, García-Sastre A, White K, Qin Y, Doench J, Yan Q, Iwasaki A, Zwaka T, Qi J, Kadoch C, Wilen C. Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection. Nature Genetics 2023, 55: 471-483. PMID: 36894709, PMCID: PMC10011139, DOI: 10.1038/s41588-023-01307-z.Peer-Reviewed Original ResearchConceptsMSWI/SNF complexesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionHost-directed therapeutic targetSyndrome coronavirus 2 infectionSARS-CoV-2 infectionSWItch/Sucrose Non-Fermentable (SWI/SNF) chromatinSARS-CoV-2 susceptibilityNon-fermentable (SWI/SNF) chromatinCoronavirus 2 infectionEnzyme 2 (ACE2) expressionSARS-CoV-2 variantsHuman cell typesPrimary human cell typesAirway epithelial cellsDrug-resistant variantsNew drug targetsChromatin accessibilitySNF complexACE2 locusACE2 expressionFactor complexHost determinantsTherapeutic targetConfer resistance
2017
Norovirus Cell Tropism Is Determined by Combinatorial Action of a Viral Non-structural Protein and Host Cytokine
Lee S, Wilen CB, Orvedahl A, McCune BT, Kim KW, Orchard RC, Peterson ST, Nice TJ, Baldridge MT, Virgin HW. Norovirus Cell Tropism Is Determined by Combinatorial Action of a Viral Non-structural Protein and Host Cytokine. Cell Host & Microbe 2017, 22: 449-459.e4. PMID: 28966054, PMCID: PMC5679710, DOI: 10.1016/j.chom.2017.08.021.Peer-Reviewed Original ResearchConceptsIntestinal epithelial cellsViral surface proteinsCellular tropismPersistent viral infectionNon-structural protein NS1Expression of NS1MNoV infectionSurface proteinsHost cytokinesAntiviral immunityHost determinantsInterferon lambdaViral infectionKey host determinantsViral non-structural proteinsCell tropismFecal sheddingNon-structural proteinsTropism determinantsEpithelial cellsGlobal causeInfectionTropismProtein NS1MNoV
2010
HIV-1 Resistance to CCR5 Antagonists Associated with Highly Efficient Use of CCR5 and Altered Tropism on Primary CD4+ T Cells
Pfaff JM, Wilen CB, Harrison JE, Demarest JF, Lee B, Doms RW, Tilton JC. HIV-1 Resistance to CCR5 Antagonists Associated with Highly Efficient Use of CCR5 and Altered Tropism on Primary CD4+ T Cells. Journal Of Virology 2010, 84: 6505-6514. PMID: 20410277, PMCID: PMC2903254, DOI: 10.1128/jvi.00374-10.Peer-Reviewed Original ResearchConceptsT cellsResistant virusesAntagonist aplavirocCCR5 antagonistsTropism shiftSmall-molecule CCR5 antagonistsEffector memory cellsT cell subsetsHIV-1 resistanceT cell homeostasisVirologic failureCell subsetsV3 loopPrimary CD4Virus infectionRelative sparingHost determinantsImmune functionCCR5Heterologous virusesViral resistanceViral tropismCentral memoryDrug resistanceAltered tropism