HIV infection and antiretroviral therapy lead to unfolded protein response activation

dc.creatorBorsa, Mariana
dc.creatorFerreira, Pedro L. C.
dc.creatorPetry, Andrea
dc.creatorFerreira, Luiz G. E.
dc.creatorCamargo, Maristela M.
dc.creatorBou-Habib, Dumith Chequer
dc.creatorPinto, Aguinaldo R.
dc.date2015-08-19T13:49:24Z
dc.date2015-08-19T13:49:24Z
dc.date2015
dc.date.accessioned2023-09-26T20:26:10Z
dc.date.available2023-09-26T20:26:10Z
dc.identifierBORSA, Mariana; et al. HIV infection and antiretroviral therapy lead to unfolded protein response activation. Virology Journal, v.12:77, 11p, 2015.
dc.identifier1743-422X
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/11505
dc.identifier10.1186/s12985-015-0298-0
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8856851
dc.descriptionBackground: The unfolded protein response (UPR) is one of the pathways triggered to ensure quality control of the proteins assembled in the endoplasmic reticulum (ER) when cell homeostasis is compromised. This mechanism is primarily composed of three transmembrane proteins serving as stress sensors: PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 (IRE1). These three proteins’ synergic action elicits translation and transcriptional downstream pathways, leading to less protein production and activating genes that encode important proteins in folding processes, including chaperones. Previous reports showed that viruses have evolved mechanisms to curtail or customize this UPR signaling for their own benefit. However, HIV infection’s effect on the UPR has scarcely been investigated. Methods: This work investigated UPR modulation by HIV infection by assessing UPR-related protein expression under in vitro and in vivo conditions via Western blotting. Antiretroviral (ARV) drugs’ influence on this stress response was also considered. Results: In in vitro and in vivo analyses, our results confirm that HIV infection activates stress-response components and that ARV therapy contributes to changes in the UPR’s activation profile. Conclusions: This is the first report showing UPR-related protein expression in HIV target cells derived directly from HIV-infected patients receiving different ARV therapies. Thus, two mechanisms may occur simultaneously: interference by HIV itself and the ARV drugs’ pharmacological effects as UPR activators. New evidence of how HIV modulates the UPR to enhance its own replication and secure infection success is also presented.
dc.formatapplication/pdf
dc.languageeng
dc.publisherBioMed Central
dc.rightsopen access
dc.subjectHIV
dc.subjectAIDS
dc.subjectUPR pathway
dc.subjectEndoplasmic reticulum stress
dc.subjectAntiretroviral therapy
dc.subjectCell stress
dc.subjectHIV
dc.subjectSíndrome de Imunodeficiência Adquirida
dc.subjectEstresse do Retículo Endoplasmático
dc.subjectTerapia Antirretroviral de Alta Atividade
dc.titleHIV infection and antiretroviral therapy lead to unfolded protein response activation
dc.typeArticle


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