biostudies-literaturePerera MRMedical Research Council543-553https://www.ebi.ac.uk/biostudies/studies/S-EPMC9927080biostudies-literatureUnknown227(4)Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused widespread morbidity and mortality since its onset in late 2019. Here, we demonstrate that prior infection with human cytomegalovirus (HCMV) substantially increases infection with SARS-CoV-2 in vitro. HCMV is a common herpesvirus carried by 40%-100% of the population, which can reactivate in the lung under inflammatory conditions, such as those resulting from SARS-CoV-2 infection. We show in both endothelial and epithelial cell types that HCMV infection upregulates ACE2, the SARS-CoV-2 cell entry receptor. These observations suggest that HCMV reactivation events in the lung of healthy HCMV carriers could exacerbate SARS-CoV-2 infection and subsequent COVID-19The Journal of infectious diseasesHuman Cytomegalovirus Infection of Epithelial Cells Increases SARS-CoV-2 Superinfection by Upregulating the ACE2 Receptor.PMC9927080RG86932MR/S00081X/1Allison JFurlong AWills MRStark HPointon LDunmore BJO'Brien Cdi Stefano GPhelan IPatterson CRossi SPolwarth GKennet JMartin JPublico CDomingo JHuhn OHunter KChandler MOmarjee OJosipovic MPerera MWalker NChinnery PFHein SMoulton ACalder JIvers TEpping MFawke SDougan GKourampa JDe Bie EMDDMescia FRichoz NAnsaripour AGraf SSutcliffe RClapham-Riley DSummers CDe Sa AMatara CJones EGeorge ACrozier TWMCrump CMMeadows ASinclair JHLyons PACambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research COVID BioResource CollaborationBunclark KTurner LSelvan MGupta RMuldoon FPrice JLinger RLehner PJTong ZKingston NParaschiv RFernandez CGray JJose SWood JNice FBergamaschi LBaker SMarsden JMackay MBradley JPolgarova PBullman BHess CHuang CRastall RRuffolo VWeekes MPPapadia SHodgson JMichael ABiggs HSaunders CSmith KGCCaputo DTreacy CElmer ASambrook JPerera MRElder EGWylot MJarvis IButcher HRanganath VTordesillas HTilly TSharma RWebster JGreenwood EJDRibeiro CTownsend PPenkett CSpencer SOwehand WHBower GSchon KCanna LDewhurst EGresley ELOkecha GPond NLegchenko EBetancourt AHewitt SRowlands JStirrups KEToshner MJackson SThaventhiran JEDvon Ziegenweidt JBucke AKasanicki MGoodfellow IMeloy SOvington NO'Donnell CShih JSchmitt JDean AMMwaura LFuller SMatheson NJHarris JYong CGraves BfalseHuman Cytomegalovirus Infection of Epithelial Cells Increases SARS-CoV-2 Superinfection by Upregulating the ACE2 Receptor.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused widespread morbidity and mortality since its onset in late 2019. Here, we demonstrate that prior infection with human cytomegalovirus (HCMV) substantially increases infection with SARS-CoV-2 in vitro. HCMV is a common herpesvirus carried by 40%-100% of the population, which can reactivate in the lung under inflammatory conditions, such as those resulting from SARS-CoV-2 infection. We show in both endothelial and epithelial cell types that HCMV infection upregulates ACE2, the SARS-CoV-2 cell entry receptor. These observations suggest that HCMV reactivation events in the lung of healthy HCMV carriers could exacerbate SARS-CoV-2 infection and subsequent COVID-192023-01-01T00:00:00Z2023 Feb2025-04-18T21:31:08.674Z2025-04-07T09:23:31.458ZS-EPMC99270803640860710.1093/infdis/jiac452