SARS-CoV-2 infection and replication kinetics in different human cell types: The role of autophagy, cellular metabolism and ACE2 expression

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dc.citation.volume308
dc.contributor.authorBartolomeo, Cynthia Silva [UNIFESP]
dc.contributor.authorLemes, Robertha Mariana Rodrigues [UNIFESP]
dc.contributor.authorMorais, Rafael Leite Tavares de [UNIFESP]
dc.contributor.authorPereira, Gabriela Cruz [UNIFESP]
dc.contributor.authorNunes, Tamires Alves [UNIFESP]
dc.contributor.authorCosta, Angelica Jardim [UNIFESP]
dc.contributor.authorMaciel, Rui Monteiro de Barros [UNIFESP]
dc.contributor.authorBraconi, Carla Torres [UNIFESP]
dc.contributor.authorMaricato, Juliana Terzi [UNIFESP]
dc.contributor.authorJanini, Luiz Mário Ramos [UNIFESP]
dc.contributor.authorOkuda, Liria Hiromi
dc.contributor.authorLee, Kil Sun [UNIFESP]
dc.contributor.authorPrado , Carla Máximo [UNIFESP]
dc.contributor.authorUreshino, Rodrigo Portes [UNIFESP]
dc.contributor.authorStilhano, Roberta Sessa
dc.contributor.authorLatteshttp://lattes.cnpq.br/1740478426977844
dc.contributor.authorLatteshttp://lattes.cnpq.br/9682597956704119
dc.contributor.authorLatteshttp://lattes.cnpq.br/5975254446394746
dc.contributor.authorLatteshttp://lattes.cnpq.br/1212794444821641
dc.contributor.authorLatteshttp://lattes.cnpq.br/2542981501423374
dc.contributor.authorLatteshttp://lattes.cnpq.br/8517445237869609
dc.contributor.authorLatteshttp://lattes.cnpq.br/1005025547870062
dc.contributor.authorLatteshttp://lattes.cnpq.br/3864261034300240
dc.contributor.authorLatteshttp://lattes.cnpq.br/6342740138292278
dc.contributor.authorLatteshttp://lattes.cnpq.br/8321096323728598
dc.contributor.authorLatteshttp://lattes.cnpq.br/5713863164263481
dc.contributor.authorLatteshttp://lattes.cnpq.br/4546671040397891
dc.contributor.authorLatteshttp://lattes.cnpq.br/7705881286363327
dc.contributor.authorLatteshttp://lattes.cnpq.br/1740478426977844
dc.contributor.authorLatteshttp://lattes.cnpq.br/7174742745591377
dc.contributor.authorLatteshttp://lattes.cnpq.br/2122125365795721
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2024-07-04T16:45:31Z
dc.date.available2024-07-04T16:45:31Z
dc.date.issued2022-09-06
dc.description.abstractAims: This study evaluated SARS-CoV-2 replication in human cell lines derived from various tissues and inves­ tigated molecular mechanisms related to viral infection susceptibility and replication. Main methods: SARS-CoV-2 replication in BEAS-2B and A549 (respiratory tract), HEK-293 T (kidney), HuH7 (liver), SH-SY5Y (brain), MCF7 (breast), Huvec (endothelial) and Caco-2 (intestine) was evaluated by RT-qPCR. Concomitantly, expression levels of ACE2 (Angiotensin Converting Enzyme) and TMPRSS2 were assessed through RT-qPCR and western blot. Proteins related to autophagy and mitochondrial metabolism were moni­tored in uninfected cells to characterize the cellular metabolism of each cell line. The effect of ACE2 over­ expression on viral replication in pulmonary cells was also investigated. Key findings: Our data show that HuH7, Caco-2 and MCF7 presented a higher viral load compared to the other cell lines. The increased susceptibility to SARS-CoV-2 infection seems to be associated not only with the differential levels of proteins intrinsically related to energetic metabolism, such as ATP synthase, citrate synthase, COX and NDUFS2 but also with the considerably higher TMPRSS2 mRNA expression. The two least susceptible cell types, BEAS-2B and A549, showed drastically increased SARS-CoV-2 replication capacity when ACE2 was overex­pressed. These modified cell lines are relevant for studying SARS-CoV-2 replication in vitro. Significance: Our data not only reinforce that TMPRSS2 expression and cellular energy metabolism are important molecular mechanisms for SARS-CoV-2 infection and replication, but also indicate that HuH7, MCF7 and Caco-2 are suitable models for mechanistic studies of COVID-19. Moreover, pulmonary cells overexpressing ACE2 can be used to understand mechanisms associated with SARS-CoV-2 replication.
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIDFAPESP: 2016/20796-2
dc.description.sponsorshipIDFAPESP: 2020/04709-8
dc.description.sponsorshipIDFAPESP: 2020/13480-4
dc.description.sponsorshipIDFAPESP: 2020/06153-7
dc.description.sponsorshipIDFAPESP: 2020/08943-5
dc.description.sponsorshipIDFAPESP: 2006/60402-1
dc.description.sponsorshipIDFAPESP: 2019/10922-9
dc.description.sponsorshipIDCAPES: code 001
dc.description.sponsorshipIDCNPq: 303035/2018-8
dc.description.sponsorshipIDCNPq: 405691/2018-1
dc.format.extent120930
dc.identifier.citationBARTOLOMEO, Cynthia Silva, LEMES, Robertha Mariana Rodrigues, MORAIS, Rafael Leite Tavares de et al. SARS-CoV-2 infection and replication kinetics in different human cell types: The role of autophagy, cellular metabolism and ACE2 expression. Life Sciences 308, 120930 (2022). https://doi.org/10.1016/j.lfs.2022.120930
dc.identifier.doihttps://doi.org/10.1016/j.lfs.2022.120930
dc.identifier.issn0024-3205
dc.identifier.urihttps://hdl.handle.net/11600/71345
dc.languageeng
dc.publisherElsevier
dc.relation.ispartofLife Science
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectCOVID-19
dc.subjectACE2
dc.subjectTMPRSS2
dc.subjectCell lines
dc.subjectMitochondria
dc.subjectAutophagy
dc.titleSARS-CoV-2 infection and replication kinetics in different human cell types: The role of autophagy, cellular metabolism and ACE2 expression
dc.typeinfo:eu-repo/semantics/article
unifesp.campusInstituto de Saúde e Sociedade (ISS)
unifesp.departamentoBiociências
unifesp.especializacaoNão se aplica
unifesp.graduacaoNão se aplica
unifesp.graduateProgramInterdisciplinar em Ciências da Saúde
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