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HIV INFECTION AND ANTIRETROVIRAL THERAPY LEAD TO UNFOLDED PROTEIN RESPONSE ACTIVATION
Síndrome de Imunodeficiência Adquirida
Estresse do Retículo Endoplasmático
Terapia Antirretroviral de Alta Atividade
Author
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
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.
DeCS
HIVSíndrome de Imunodeficiência Adquirida
Estresse do Retículo Endoplasmático
Terapia Antirretroviral de Alta Atividade
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