Cargando…
HIV infection and antiretroviral therapy lead to unfolded protein response activation
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:...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455982/ https://www.ncbi.nlm.nih.gov/pubmed/25976933 http://dx.doi.org/10.1186/s12985-015-0298-0 |
_version_ | 1782374791805665280 |
---|---|
author | Borsa, Mariana Ferreira, Pedro L. C. Petry, Andrea Ferreira, Luiz G. E. Camargo, Maristela M. Bou-Habib, Dumith Chequer Pinto, Aguinaldo R. |
author_facet | Borsa, Mariana Ferreira, Pedro L. C. Petry, Andrea Ferreira, Luiz G. E. Camargo, Maristela M. Bou-Habib, Dumith Chequer Pinto, Aguinaldo R. |
author_sort | Borsa, Mariana |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0298-0) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4455982 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44559822015-06-05 HIV infection and antiretroviral therapy lead to unfolded protein response activation Borsa, Mariana Ferreira, Pedro L. C. Petry, Andrea Ferreira, Luiz G. E. Camargo, Maristela M. Bou-Habib, Dumith Chequer Pinto, Aguinaldo R. Virol J Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0298-0) contains supplementary material, which is available to authorized users. BioMed Central 2015-05-15 /pmc/articles/PMC4455982/ /pubmed/25976933 http://dx.doi.org/10.1186/s12985-015-0298-0 Text en © Borsa et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Borsa, Mariana Ferreira, Pedro L. C. Petry, Andrea Ferreira, Luiz G. E. Camargo, Maristela M. Bou-Habib, Dumith Chequer Pinto, Aguinaldo R. HIV infection and antiretroviral therapy lead to unfolded protein response activation |
title | HIV infection and antiretroviral therapy lead to unfolded protein response activation |
title_full | HIV infection and antiretroviral therapy lead to unfolded protein response activation |
title_fullStr | HIV infection and antiretroviral therapy lead to unfolded protein response activation |
title_full_unstemmed | HIV infection and antiretroviral therapy lead to unfolded protein response activation |
title_short | HIV infection and antiretroviral therapy lead to unfolded protein response activation |
title_sort | hiv infection and antiretroviral therapy lead to unfolded protein response activation |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455982/ https://www.ncbi.nlm.nih.gov/pubmed/25976933 http://dx.doi.org/10.1186/s12985-015-0298-0 |
work_keys_str_mv | AT borsamariana hivinfectionandantiretroviraltherapyleadtounfoldedproteinresponseactivation AT ferreirapedrolc hivinfectionandantiretroviraltherapyleadtounfoldedproteinresponseactivation AT petryandrea hivinfectionandantiretroviraltherapyleadtounfoldedproteinresponseactivation AT ferreiraluizge hivinfectionandantiretroviraltherapyleadtounfoldedproteinresponseactivation AT camargomaristelam hivinfectionandantiretroviraltherapyleadtounfoldedproteinresponseactivation AT bouhabibdumithchequer hivinfectionandantiretroviraltherapyleadtounfoldedproteinresponseactivation AT pintoaguinaldor hivinfectionandantiretroviraltherapyleadtounfoldedproteinresponseactivation |