Title:	HIV infection and antiretroviral therapy lead to unfolded protein response activation
Authors:	Borsa, Mariana Ferreira, Pedro L. C. Petry, Andrea Ferreira, Luiz G. E. Camargo, Maristela M. Bou-Habib, Dumith Chequer Pinto, Aguinaldo R.
Affilliation:	Universidade Federal de Santa Catarina. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Imunologia Aplicada. Florianópolis, SC, Brasil. Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisas sobre o Timo. Rio de Janeiro, RJ, Brasil. Centro de Hematologia e Hemoterapia de Santa Catarina. Florianópolis, SC, Brasil. Hospital Regional Homero de Miranda Gomes. São José, SC, Brasil. Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Imunologia. São Paulo, Sp, Brasil
Abstract:	Background: 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.
Keywords:	HIV AIDS UPR pathway Endoplasmic reticulum stress Antiretroviral therapy Cell stress
DeCS:	HIV Síndrome de Imunodeficiência Adquirida Estresse do Retículo Endoplasmático Terapia Antirretroviral de Alta Atividade
Issue Date:	2015
Publisher:	BioMed Central
Citation:	BORSA, Mariana; et al. HIV infection and antiretroviral therapy lead to unfolded protein response activation. Virology Journal, v.12:77, 11p, 2015.
DOI:	10.1186/s12985-015-0298-0
ISSN:	1743-422X
Copyright:	open access
Appears in Collections:	IOC - Artigos de Periódicos

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