Repositorio Institucional Académico. Universidad Andrés Bello. Chile

Examinando por Autor "Duarte, Luisa F."

Mostrando 1 - 11 de 11

Asymptomatic herpes simplex virus brain infection elicits cellular senescence phenotypes in the central nervous system of mice suffering multiple sclerosis-like disease
(Communications Biology, Volume 7, Issue 1 December 2024, Article number 81, 2024-12) Duarte, Luisa F.; Villalobos, Verónica; Farías, Mónica A.; Rangel-Ramírez, Ma. Andreina; González-Madrid, Enrique; Navarro, Areli J.; Carbone-Schellman, Javier; Domínguez, Angélica; Alvarez, Alejandra; Riedel, Claudia A.; Bueno, Susan M.; Kalergis, Alexis M.
Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease affecting the central nervous system (CNS) in animals that parallels several clinical and molecular traits of multiple sclerosis in humans. Herpes simplex virus type 1 (HSV-1) infection mainly causes cold sores and eye diseases, yet eventually, it can also reach the CNS, leading to acute encephalitis. Notably, a significant proportion of healthy individuals are likely to have asymptomatic HSV-1 brain infection with chronic brain inflammation due to persistent latent infection in neurons. Because cellular senescence is suggested as a potential factor contributing to the development of various neurodegenerative disorders, including multiple sclerosis, and viral infections may induce a premature senescence state in the CNS, potentially increasing susceptibility to such disorders, here we examine the presence of senescence-related markers in the brains and spinal cords of mice with asymptomatic HSV-1 brain infection, EAE, and both conditions. Across all scenarios, we find a significant increases of senescence biomarkers in the CNS with some differences depending on the analyzed group. Notably, some senescence biomarkers are exclusively observed in mice with the combined conditions. These results indicate that asymptomatic HSV-1 brain infection and EAE associate with a significant expression of senescence biomarkers in the CNS. © The Author(s) 2024.
Asymptomatic Herpes Simplex Virus Type 1 Infection Causes an Earlier Onset and More Severe Experimental Autoimmune Encephalomyelitis
(Frontiers Media S.A., 2021-02) Duarte, Luisa F.; Altamirano Lagos, María J.; Tabares Guevara, Jorge H.; Opazo, Ma. Cecilia; Díaz, Máximo; Navarrete, Romina; Muza, Catalina; Vallejos, Omar P.; Riedel, Claudia A.; Bueno, Susan M.; Kalergis, Alexis M.; González, Pablo A.
Multiple sclerosis (MS) is an increasingly prevalent progressive autoimmune and debilitating chronic disease that involves the detrimental recognition of central nervous system (CNS) antigens by the immune system. Although significant progress has been made in the last decades on the biology of MS and the identification of novel therapies to treat its symptoms, the etiology of this disease remains unknown. However, recent studies have suggested that viral infections may contribute to disease onset. Interestingly, a potential association between herpes simplex virus type 1 (HSV-1) infection and MS has been reported, yet a direct relationship among both has not been conclusively demonstrated. Experimental autoimmune encephalomyelitis (EAE) recapitulates several aspects of MS in humans and is widely used to study this disease. Here, we evaluated the effect of asymptomatic brain infection by HSV-1 on the onset and severity of EAE in C57BL/6 mice. We also evaluated the effect of infection with an HSV-1-mutant that is attenuated in neurovirulence and does not cause encephalitis. Importantly, we observed more severe EAE in mice previously infected either, with the wild-type (WT) or the mutant HSV-1, as compared to uninfected control mice. Also, earlier EAE onset was seen after WT virus inoculation. These findings support the notion that a previous exposure to HSV-1 can accelerate and enhance EAE, which suggests a potential contribution of asymptomatic HSV-1 to the onset and severity of MS. © Copyright © 2021 Duarte, Altamirano-Lagos, Tabares-Guevara, Opazo, Díaz, Navarrete, Muza, Vallejos, Riedel, Bueno, Kalergis and González.
Contribution of viral and bacterial infections to senescence and immunosenescence
(Frontiers Media SA, 2023) Reyes, Antonia; Ortiz, Gerardo; Duarte, Luisa F.; Fernández, Christian; Hernández-Armengol, Rosario; Palacios, Pablo A.; Prado, Yolanda; Andrade, Catalina A.; Rodriguez-Guilarte, Linmar; Kalergis, Alexis M.; Simon, Felipe; Carreño, Leandro J.; Riedel, Claudia A.; Cáceres, Mónica; González, Pablo A.
Cellular senescence is a key biological process characterized by irreversible cell cycle arrest. The accumulation of senescent cells creates a pro-inflammatory environment that can negatively affect tissue functions and may promote the development of aging-related diseases. Typical biomarkers related to senescence include senescence-associated β-galactosidase activity, histone H2A.X phosphorylation at serine139 (γH2A.X), and senescence-associated heterochromatin foci (SAHF) with heterochromatin protein 1γ (HP-1γ protein) Moreover, immune cells undergoing senescence, which is known as immunosenescence, can affect innate and adaptative immune functions and may elicit detrimental effects over the host’s susceptibility to infectious diseases. Although associations between senescence and pathogens have been reported, clear links between both, and the related molecular mechanisms involved remain to be determined. Furthermore, it remains to be determined whether infections effectively induce senescence, the impact of senescence and immunosenescence over infections, or if both events coincidently share common molecular markers, such as γH2A.X and p53. Here, we review and discuss the most recent reports that describe cellular hallmarks and biomarkers related to senescence in immune and non-immune cells in the context of infections, seeking to better understand their relationships. Related literature was searched in Pubmed and Google Scholar databases with search terms related to the sections and subsections of this review. Copyright © 2023 Reyes, Ortiz, Duarte, Fernández, Hernández-Armengol, Palacios, Prado, Andrade, Rodriguez-Guilarte, Kalergis, Simon, Carreño, Riedel, Cáceres and González.
Differences in the immune response elicited by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial
(eLife Sciences Publications Ltd, 2022) Gálvez, Nicolás M. S.; Pacheco, Gaspar A.; Schultz, Bárbara M.; Melo-González, Felipe; Soto, Jorge A.; Duarte, Luisa F.; González, Liliana A.; Rivera-Pérez, Daniela; Ríos, Mariana; Berrios, Roslye V.; Vázquez, Yaneisi; Moreno-Tapia, Daniela; Vallejos, Omar P.; Andrade, Catalina A.; Hoppe-Elsholz, Guillermo; Iturriaga, Carolina; Urzua, Marcela; Navarrete, María S.; Rojas, Álvaro; Fasce, Rodrigo; Fernández, Jorge; Mora, Judith; Ramírez, Eugenio; Gaete-Argel, Aracelly; Acevedo, Mónica L.; Valiente-Echeverría, Fernando; Soto-Rifo, Ricardo; Weiskopf, Daniela; Grifoni, Alba; Sette, Alessandro; Zeng, Gang; Meng, Weining; González-Aramundiz, José V.; Johnson, Marina; Goldblatt, David; González, Pablo A.; Abarca, Katia; Bueno, Susan M.; Kalergis, Alexis M.
Background: The development of vaccines to control the coronavirus disease 2019 (COVID-19) pandemic progression is a worldwide priority. CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine approved for emergency use with robust efficacy and immunogenicity data reported in trials in China, Brazil, Indonesia, Turkey, and Chile. Methods: This study is a randomized, multicenter, and controlled phase 3 trial in healthy Chilean adults aged ≥18 years. Volunteers received two doses of CoronaVac separated by 2 (0–14 schedule) or 4 weeks (0–28 schedule); 2302 volunteers were enrolled, 440 were part of the immunogenicity arm, and blood samples were obtained at different times. Samples from a single center are reported. Humoral immune responses were evaluated by measuring the neutralizing capacities of circulating antibodies. Cellular immune responses were assessed by ELISPOT and flow cytometry. Correlation matrixes were performed to evaluate correlations in the data measured. Results: Both schedules exhibited robust neutralizing capacities with the response induced by the 0–28 schedule being better. No differences were found in the concentration of antibodies against the virus and different variants of concern (VOCs) between schedules. Stimulation of peripheral blood mononuclear cells (PBMCs) with Mega pools of Peptides (MPs) induced the secretion of interferon (IFN)-γ and the expression of activation induced markers in CD4+ T cells for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-γ secretion. Conclusions: Immunization with CoronaVac in Chilean adults promotes robust cellular and humoral immune responses. The 0–28 schedule induced a stronger humoral immune response than the 0–14 schedule. © Gálvez, Pacheco, Schultz et al.
Differential Severe Acute Respiratory Syndrome Coronavirus 2-Specific Humoral Response in Inactivated Virus-Vaccinated, Convalescent, and Breakthrough-Infected Subjects
(Oxford University Press, 2023-10-01) Duarte, Luisa F.; Vázquez, Yaneisi; Diethelm-Varela, Benjamín; Pavez, Valentina; Berríos-Rojas, Roslye; Méndez, Constanza; Riedel, Claudia A.; White, Jessica A.; Kalergis, Alexis M.; Bueno, Susan M.; González, Pablo A.
Background: We sought to identify potential antigens for discerning between humoral responses elicited after vaccination with CoronaVac (a severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] inactivated vaccine), natural infection, or breakthrough infection. Methods: Serum samples obtained from volunteers immunized with CoronaVac (2 and 3 doses), breakthrough case patients, and from convalescent individuals were analyzed to determine the immunoglobulin (Ig) G responses against 3 structural and 8 nonstructural SARS-CoV-2 antigens. Results: Immunization with CoronaVac induced higher levels of antibodies against the viral membrane (M) protein compared with convalescent subjects both after primary vaccination and after a booster dose. Individuals receiving a booster dose displayed equivalent levels of IgG antibodies against the nucleocapsid (N) protein, similar to convalescent subjects. Breakthrough case patients produced the highest antibody levels against the N and M proteins. Antibodies against nonstructural viral proteins were present in >50% of the convalescent subjects. Conclusions: Vaccinated individuals elicited a different humoral response compared to convalescent subjects. The analysis of particular SARS-CoV-2 antigens could be used as biomarkers for determining infection in subjects previously vaccinated with CoronaVac. © 2023 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America.
Heme Oxygenase-1 Expression in Dendritic Cells Contributes to Protective Immunity against Herpes Simplex Virus Skin Infection
(MDPI, 2023-05) Tognarelli, Eduardo I.; Duarte, Luisa F.; Farías, Mónica A.; Cancino, Felipe A.; Corrales, Nicolás; Ibáñez, Francisco J.; Riedel, Claudia A.; Bueno, Susan M.; Kalergis, Alexis M.; González, Pablo A.
Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections are highly prevalent in the human population and produce mild to life-threatening diseases. These viruses interfere with the function and viability of dendritic cells (DCs), which are professional antigen-presenting cells that initiate and regulate the host’s antiviral immune responses. Heme oxygenase-1 (HO-1) is an inducible host enzyme with reported antiviral activity against HSVs in epithelial cells and neurons. Here, we sought to assess whether HO-1 modulates the function and viability of DCs upon infection with HSV-1 or HSV-2. We found that the stimulation of HO-1 expression in HSV-inoculated DCs significantly recovered the viability of these cells and hampered viral egress. Furthermore, HSV-infected DCs stimulated to express HO-1 promoted the expression of anti-inflammatory molecules, such as PDL-1 and IL-10, and the activation of virus-specific CD4+ T cells with regulatory (Treg), Th17 and Treg/Th17 phenotypes. Moreover, HSV-infected DCs stimulated to express HO-1 and then transferred into mice, promoted the activation of virus-specific T cells and improved the outcome of HSV-1 skin infection. These findings suggest that stimulation of HO-1 expression in DCs limits the deleterious effects of HSVs over these cells and induces a favorable virus-specific immune response in the skin against HSV-1. © 2023 by the authors.
Humoral and cellular response induced by a second booster of an inactivated SARS-CoV-2 vaccine in adults
(Elsevier B.V., 2023-05) Méndez, Constanza; Peñaloza, Hernán F.; Schultz, Bárbara M.; Piña-Iturbe, Alejandro; Ríos, Mariana; Moreno-Tapia, Daniela; Pereira-Sánchez, Patricia; Leighton, Diane; Orellana, Claudia; Covarrubias, Consuelo; Gálvez, Nicolás M.S.; Soto, Jorge A.; Duarte, Luisa F.; Rivera-Pérez, Daniela; Vázquez, Yaneisi; Cabrera, Alex; Bustos, Sergio; Iturriaga, Carolina; Urzua, Marcela; Navarrete, María S.; Rojas, Álvaro; Fasce, Rodrigo A.; Fernández, Jorge; Mora, Judith; Ramírez, Eugenio; Gaete-Argel, Aracelly; Acevedo, Mónica; Valiente-Echeverría, Fernando; Soto-Rifo, Ricardo; Weiskopf, Daniela; Grifoni, Alba; Sette, Alessandro; Zeng, Gang; Meng, Weining; Del Río, Constanza; Del Pino, Dinely; Aguirre, Natalia; Salinas, Grecia; Vega, Franco; Salgado, Acsa; Quinteros, Thomas; Ortiz, Marlene; Puente, Marcela; Muñoz, Alma; Astudillo, Patricio; Le Corre, Nicole; Potin, Marcela; Catalán, Juan; Peralta, Melan; Zamanillo, Consuelo; Keller, Nicole; Fernández, Rocío; Aljaro, Sofía; López, Sofía; González, José Tomás; Weil, Tania; Opazo, Luz; Muñoz, Paula; Estay, Inés; Cantillana, Miguel; Carrera, Liliana; Masalleras, Matías; Guzmán, Paula; Aguirre, Francisca; Cortés, Aarón; Bátiz, Luis Federico; Pérez, Javiera; Apablaza, Karen; Yates, Lorena; Valdés, María de los Ángeles; Hurtado, Bernardita; Venteneul, Veronique; Astorga, Constanza; Muñoz-Venturelli, Paula; Vial, Pablo A.; Schilling, Andrea; Pavez, Daniela; Pérez, Inia; Riviotta, Amy; González, Francisca; Urrutia, Francisca; Del Río, Alejandra; Asenjo, Claudia; Vargas, Bárbara; Castro, Francisca; Acuña, Alejandra; Guzmán, Javiera; Astudillo, Camila; Pérez, Carlos M.; Espinoza, Pilar; Martínez, Andrea; Arancibia, Marcela; Romero, Harold; Bustamante, Cecilia; Pérez, María Loreto; Uribe, Natalia; Silva, Viviana; Morice, Bernardita; Pérez, Marco; González, Marcela; Jensen, Werner; Pasten, Claudia; Aguilera, M. Fernanda; Martínez, Nataly; Molina, Camila; Arrieta, Sebastián; López, Begoña; Ortiz, Claudia; Escobar, Macarena; Bustamante, Camila; Espinoza, Marcia; Pardo, Angela; Carrasco, Alison; Montes, Miguel; Saldías, Macarena; Gutiérrez, Natalia; Sánchez, Juliette; Fuentes, Daniela; Calvo, Yolanda; Cepeda, Mariela; Lemus, Rosario; Suárez, Muriel; Armijo, Mercedes; Monsalves, Shirley; Marucich, Constance; Cornejo, Cecilia; Acosta, Ángela; Prado, Xaviera; Yáñez, Francisca; Barroeta, Marisol; López, Claudia; Donato, Paulina; Lasso, Martin; Iturrieta, María; Giraldo, Juan; Gutiérrez, Francisco; Acuña, María; Cascone, Ada; Rojas, Raymundo; Sepúlveda, Camila; Contreras, Mario; Campisto, Yessica; González, Pablo A.; Quizhpi, Zoila; López, Mariella; Pizzeghello, Vania; Silva, Stephannie; González-Aramundiz, José V.; Abarca, Katia; Melo-González, Felipe; Bueno, Susan M.; Kalergis, Alexis M.
Background: The Omicron variant has challenged the control of the COVID-19 pandemic due to its immuno-evasive properties. The administration of a booster dose of a SARS-CoV-2 vaccine showed positive effects in the immunogenicity against SARS-CoV-2, effect that is even enhanced after the administration of a second booster. Methods: During a phase-3 clinical trial, we evaluated the effect of a second booster of CoronaVac®, an inactivated vaccine administered 6 months after the first booster, in the neutralization of SARS-CoV-2 (n = 87). In parallel, cellular immunity (n = 45) was analyzed in stimulated peripheral mononuclear cells by flow cytometry and ELISPOT. Findings: Although a 2.5-fold increase in neutralization of the ancestral SARS-CoV-2 was observed after the second booster when compared with prior its administration (Geometric mean units p < 0.0001; Geometric mean titer p = 0.0002), a poor neutralization against the Omicron variant was detected. Additionally, the activation of specific CD4+ T lymphocytes remained stable after the second booster and, importantly, equivalent activation of CD4+ T lymphocytes against the Omicron variant and the ancestral SARS-CoV-2 were found. Interpretation: Although the neutralizing response against the Omicron variant after the second booster of CoronaVac® was slightly increased, these levels are far from those observed against the ancestral SARS-CoV-2 and could most likely fail to neutralize the virus. In contrast, a robust CD4+T cell response may confer protection against the Omicron variant. Funding: The Ministry of Health, Government of Chile, the Confederation of Production and Commerce, Chile and SINOVAC Biotech. NIH NIAID. The Millennium Institute on Immunology and Immunotherapy. © 2023 The Author(s)
IL-10-Dependent Amelioration of Chronic Inflammatory Disease by Microdose Subcutaneous Delivery of a Prototypic Immunoregulatory Small Molecule
(Frontiers Media S.A., 2021-07) Tabares Guevara, Jorge H.; Jaramillo, Julio C.; Ospina Quintero, Laura; Piedrahíta Ochoa, Christian A.; García Valencia, Natalia; Bautista Erazo, David E.; Caro Gómez, Erika; Covián, Camila; Retamal Díaz, Angello; Duarte, Luisa F.; González, Pablo A.; Bueno, Susan M.; Riedel, Claudia A.; Kalergis, Alexis M.; Ramírez Pineda, José R.
One of the interventional strategies to reestablish the immune effector/regulatory balance, that is typically altered in chronic inflammatory diseases (CID), is the reinforcement of endogenous immunomodulatory pathways as the one triggered by interleukin (IL)-10. In a recent work, we demonstrated that the subcutaneous (sc) administration of an IL-10/Treg-inducing small molecule-based formulation, using a repetitive microdose (REMID) treatment strategy to preferentially direct the effects to the regional immune system, delays the progression of atherosclerosis. Here we investigated whether the same approach using other IL-10-inducing small molecule, such as the safe, inexpensive, and widely available polyphenol curcumin, could induce a similar protective effect in two different CID models. We found that, in apolipoprotein E deficient mice, sc treatment with curcumin following the REMID strategy induced atheroprotection that was not consequence of its direct systemic lipid-modifying or antioxidant activity, but instead paralleled immunomodulatory effects, such as reduced proatherogenic IFNγ/TNFα-producing cells and increased atheroprotective FOXP3+ Tregs and IL-10-producing dendritic and B cells. Remarkably, when a similar strategy was used in the neuroinflammatory model of experimental autoimmune encephalomyelitis (EAE), significant clinical and histopathological protective effects were evidenced, and these were related to an improved effector/regulatory cytokine balance in restimulated splenocytes. The essential role of curcumin-induced IL-10 for neuroprotection was confirmed by the complete abrogation of the clinical effects in IL-10-deficient mice. Finally, the translational therapeutic prospection of this strategy was evidenced by the neuroprotection observed in mice starting the treatment one week after disease triggering. Collectively, results demonstrate the power of a simple natural IL-10-inducing small molecule to tackle chronic inflammation, when its classical systemic and direct pharmacological view is shifted towards the targeting of regional immune cells, in order to rationally harness its immunopharmacological potential. This shift implies that many well-known IL-10-inducing small molecules could be easily reformulated and repurposed to develop safe, innovative, and accessible immune-based interventions for CID. © Copyright © 2021 Tabares-Guevara, Jaramillo, Ospina-Quintero, Piedrahíta-Ochoa, García-Valencia, Bautista-Erazo, Caro-Gómez, Covián, Retamal-Díaz, Duarte, González, Bueno, Riedel, Kalergis and Ramírez-Pineda.
Inactivated Vaccine-Induced SARS-CoV-2 Variant-Specific Immunity in Children
(American Society for Microbiology, 2022-12) Soto, Jorge A.; Melo González, Felipe; Gutierrez Vera, Cristián; Schultz, Bárbara M.; Berríos Rojas, Roslye V.; Rivera Pérez, Daniela; Piña Iturbe, Alejandro; Hoppe Elsholz, Guillermo; Duarte, Luisa F.; Vázquez, Yaneisi; Moreno Tapia, Daniela; Ríos, Mariana; Palacios, Pablo A.; Garcia Betancourt, Richard; Santibañez, Álvaro; Pacheco, Gaspar A.; Mendez, Constanza; Andrade, Catalina A.; Silva, Pedro H.; Diethelm Varela, Benjamín; Astudillo, Patricio; Calvo, Mario; Cárdenas, Antonio; González, Marcela; Goldsack, Macarena; Gutiérrez, Valentina; Potin, Marcela; Schilling, Andrea; Tapia, Lorena I.; Twele, Loreto; Villena, Rodolfo; Grifoni, Albar; Sette, Alessandro; Weiskopf, Daniela; Fasce, Rodrigo A.; Fernández, Jorge; Mora, Judith; Ramírez, Eugenio; Gaete Argel, Aracelly; Acevedo, Mónica L.; Valiente Echeverría, Fernando; Soto Rifo, Ricardo; Retamal Díaz, Angello; Muñoz Jofré, Nathalia; Meng, Xing; Xin, Qianqian; Alarcón Bustamante, Eduardo; González Aramundiz, José V.; Le Corre, Nicole; Álvarez Figueroa, María Javiera; González, Pablo A.; Abarca, Katia; Perret, Cecilia; Carreño, Leandro J.; Bueno, Susan M.; Kalergis, Alexis M.
Multiple vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been evaluated in clinical trials. However, trials addressing the immune response in the pediatric population are scarce. The inactivated vaccine CoronaVac has been shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. Here, we report interim safety and immunogenicity results of a phase 3 clinical trial for CoronaVac in healthy children and adolescents in Chile. Participants 3 to 17 years old received two doses of CoronaVac in a 4-week interval until 31 December 2021. Local and systemic adverse reactions were registered for volunteers who received one or two doses of CoronaVac. Whole-blood samples were collected from a subgroup of 148 participants for humoral and cellular immunity analyses. The main adverse reaction reported after the first and second doses was pain at the injection site. Four weeks after the second dose, an increase in neutralizing antibody titer was observed in subjects relative to their baseline visit. Similar results were found for activation of specific CD41 T cells. Neutralizing antibodies were identified against the Delta and Omicron variants. However, these titers were lower than those for the D614G strain. Importantly, comparable CD41 T cell responses were detected against these variants of concern. Therefore, CoronaVac is safe and immunogenic in subjects 3 to 17 years old, inducing neutralizing antibody secretion and activating CD41 T cells against SARS-CoV-2 and its variants. (This study has been registered at ClinicalTrials .gov under no. NCT04992260.) IMPORTANCE This work evaluated the immune response induced by two doses of CoronaVac separated by 4 weeks in healthy children and adolescents in Chile. To date, few studies have described the effects of CoronaVac in the pediatric population. Therefore, it is essential to generate knowledge regarding the protection of vaccines in this population. Along these lines, we reported the anti-S humoral response and cellular immune response to several SARS-CoV-2 proteins that have been published and recently studied. Here, we show that a vaccination schedule consisting of two doses separated by 4 weeks induces the secretion of neutralizing antibodies against SARS-CoV-2. Furthermore, CoronaVac induces the activation of CD41 T cells upon stimulation with peptides from the proteome of SARS-CoV-2. These results indicate that, even though the neutralizing antibody response induced by vaccination decreases against the Delta and Omicron variants, the cellular response against these variants is comparable to the response against the ancestral strain D614G, even being significantly higher against Omicron. Copyright © 2022 Soto et al.
Is there a role for herpes simplex virus type 1 in multiple sclerosis?
(Elsevier Masson s.r.l., 2023-06) Duarte, Luisa F.; Gatica, Sebastian; Castillo, Almendra; Kalergis, Alexis M.; Bueno, Susan M.; Riedel, Claudia A.; González, Pablo A.
Numerous studies relate the onset and severity of multiple sclerosis (MS) with viral infections. Herpes simplex virus type 1 (HSV-1), which is neurotropic and highly prevalent in the brain of healthy in dividuals, has been proposed to relate to MS. Here, we review and discuss the reported connections between HSV-1 and MS. © 2022 The Author(s). Published by Elsevier Masson SAS on behalf of Institut Pasteur. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Pharmacological Inhibition of IRE-1 Alpha Activity in Herpes Simplex Virus Type 1 and Type 2-Infected Dendritic Cells Enhances T Cell Activation
(Frontiers Media S.A. Original language, 2022-01) Tognarelli, Eduardo I.; Retamal Díaz, Angello; Farías, Mónica A.; Duarte, Luisa F.; Palomino, Tomás F.; Ibañez, Francisco J.; Riedel, Claudia A.; Kalergis, Alexis M.; Bueno, Susan M.; González, Pablo A.
Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections are life-long and highly prevalent in the human population. These viruses persist in the host, eliciting either symptomatic or asymptomatic infections that may occur sporadically or in a recurrent manner through viral reactivations. Clinical manifestations due to symptomatic infection may be mild such as orofacial lesions, but may also translate into more severe diseases, such as ocular infections that may lead to blindness and life-threatening encephalitis. A key feature of herpes simplex viruses (HSVs) is that they have evolved molecular determinants that hamper numerous components of the host’s antiviral innate and adaptive immune system. Importantly, HSVs infect and negatively modulate the function of dendritic cells (DCs), by inhibiting their T cell-activating capacity and eliciting their apoptosis after infection. Previously, we reported that HSV-2 activates the splicing of the mRNA of XBP1, which is related to the activity of the unfolded protein response (UPR) factor Inositol-Requiring Enzyme 1 alpha (IRE-1α). Here, we sought to evaluate if the activation of the IRE-1α pathway in DCs upon HSV infection may be related to impaired DC function after infection with HSV-1 or HSV-2. Interestingly, the pharmacological inhibition of the endonuclease activity of IRE-1α in HSV-1- and HSV-2-infected DCs significantly reduced apoptosis in these cells and enhanced their capacity to migrate to lymph nodes and activate virus-specific CD4+ and CD8+ T cells. These findings suggest that the activation of the IRE-1α-dependent UPR pathway in HSV-infected DCs may play a significant role in the negative effects that these viruses exert over these cells and that the modulation of this signaling pathway may be relevant for enhancing the function of DCs upon infection with HSVs. Copyright © 2022 Tognarelli, Retamal-Díaz, Farías, Duarte, Palomino, Ibañez, Riedel, Kalergis, Bueno and González.

Examinando por Autor "Duarte, Luisa F."

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