Browsing by Author "Duarte Peñaloza, Luisa Fernanda"
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- ItemAnti-herpetic Activity ofMacrocystis pyriferaandDurvillaea antarcticaAlgae Extracts Against HSV-1 and HSV-2(2020) Castillo, E.; Duarte Peñaloza, Luisa Fernanda; Corrales, N.; Álvarez Espejo, Diana Claudia Marcela; Farías León, Mónica Andrea; Henríquez, A.; Smith Ferrer, Patricio; Agurto Muñoz, C.; González Muñoz, Pablo Alberto
- ItemAsymptomatic Herpes Simplex Virus Type 1 Infection Causes an Earlier Onset and More Severe Experimental Autoimmune Encephalomyelitis(2021) Duarte Peñaloza, Luisa Fernanda; Altamirano Lagos, María J.; Tabares Guevara, Jorge H.; Opazo, María Cecilia; Díaz, Máximo; Navarrete, Romina; Muza, Catalina; Vallejos Galvez, Omar Patricio; Riedel Soria, Claudia; Bueno Ramírez, Susan; Kalergis Parra, Alexis Mikes; González Muñoz, Pablo AlbertoMultiple 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.
- ItemCrosstalk Between Epithelial Cells, Neurons and Immune Mediators in HSV-1 Skin Infection(2021) Duarte Peñaloza, Luisa Fernanda; Reyes Muñoz, Antonia; Farías León, Mónica; Riedel Soria, Claudia; Bueno Ramírez, Susan; Kalergis Parra, Alexis; González Adonis, Pablo AndrésHerpes simplex virus type 1 (HSV-1) infection is highly prevalent in humans, with approximately two-thirds of the world population living with this virus. However, only a fraction of those carrying HSV-1, which elicits lifelong infections, are symptomatic. HSV-1 mainly causes lesions in the skin and mucosae but reaches the termini of sensory neurons innervating these tissues and travels in a retrograde manner to the neuron cell body where it establishes persistent infection and remains in a latent state until reactivated by different stimuli. When productive reactivations occur, the virus travels back along axons to the primary infection site, where new rounds of replication are initiated in the skin, in recurrent or secondary infections. During this process, new neuron infections occur. Noteworthy, the mechanisms underlying viral reactivations and the exit of latency are somewhat poorly understood and may be regulated by a crosstalk between the infected neurons and components of the immune system. Here, we review and discuss the immune responses that occur at the skin during primary and recurrent infections by HSV-1, as well as at the interphase of latently-infected neurons. Moreover, we discuss the implications of neuronal signals over the priming and migration of immune cells in the context of HSV-1 infection.
- ItemDifferential Sars-cov-2 antigen specificity of the humoral response inactivated virus-vaccinated, convalescent, and breakthrough subjects(2022) Duarte Peñaloza, Luisa Fernanda; Vázquez Hernández, Yaneisi; Diethelm Varela, Benjamin Manuel; Pávez Carrasco, Valentina Ignacia; Berrios Rojas, Roslye; White, Jessica A.; Kalergis Parra, Alexis Mikes; Bueno Ramírez, Susan Marcela; Gonzalez Munoz, Pablo AlbertoAnalytical methods for the differential determination between natural infection with SARS- CoV-2 vs. immunity elicited by vaccination or infection after immunization (breakthrough cases) represent attractive new research venues in the context of the ongoing COVID-19 pandemic caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). Herein, we set out to compare humoral responses against several SARS-CoV-2 structural and non-structural proteins in infected unvaccinated (convalescent), vaccinated, as well as vaccinated and infected (breakthrough) individuals. Our results indicate that immunization with an inactivated SARS-CoV-2 vaccine (CoronaVac) induces significantly higher levels of IgG antibodies against the membrane (M) protein of SARS-CoV-2 as compared to convalescent subjects both, after the primary vaccination schedule and after a booster dose. Moreover, we found that CoronaVac-immunized individuals, after receiving a third vaccine shot, display equivalent levels of N-specific IgG antibodies as convalescents subjects. Regarding non-structural viral proteins, for the two viral proteins ORF3a and NSP8, IgG antibodies were produced in more than 50% of the convalescent subjects. Finally, a logistic regression model and a receiver operating characteristic (ROC) analysis show that combined detection of M and N proteins may be useful as a biomarker to differentiate breakthrough cases from vaccinated and convalescent individuals that did not receive prior vaccination. Taken together, these results suggest that multiple SARS-CoV-2 antigens may be used as differential biomarkers for distinguishing natural infection from vaccination.
- ItemDifferential Severe Acute Respiratory Syndrome Coronavirus 2-Specific Humoral Response in Inactivated Virus-Vaccinated, Convalescent, and Breakthrough-Infected Subjects(OXFORD UNIV PRESS INC, 2023) Duarte Peñaloza, Luisa Fernanda; Vazquez Hernandez Yaneisi; Diethelm Varela, Benjamin Manuel; Pavez, Valentina; Berrios-Rojas, Roslye; Riedel, Claudia A.; Mendez, Constanza; White, Jessica A.; Kalergis Parra, Alexis Mikes; Bueno Ramírez, Susan Marcela; González Muñoz, Pablo AlbertoBackground. 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.
- ItemEvaluating the impact of asymptomatic herpes simplex virus type 1 infection on multiple sclerosis disease in a mouse model(2020) Duarte Peñaloza, Luisa Fernanda; González Muñoz, Pablo Alberto; Pontificia Universidad Católica de Chile. Facultad de Ciencias BiológicasLa esclerosis múltiple es una enfermedad autoinmune desmielinizante del sistema nervioso central (SNC) que perjudica severamente las funciones sensoriales y motoras del individuo. Hoy en día, la causa o causas de esta enfermedad son desconocidas y el tratamiento disponible solo disminuye la frecuencia de las recaídas inflamatorias, pero no previene del daño crónico y el declive neurológico. Existe evidencia que sugiere que los virus pueden tener un papel importante en el inicio y la patogénesis de la esclerosis múltiple por actuar como gatillantes ambientales. Notablemente, virus que pertenecen a la familia Herpesviridae, los cuales son adquiridos en etapas tempranas de la vida y causan infecciones latentes de por vida, han sido definidos como principales candidatos para iniciar o exacerbar esta enfermedad. Actualmente, pocos estudios han evaluado el potencial papel de los virus del herpes simple en esclerosis múltiple. Cabe resaltar, que el virus del herpes simple tipo 1 (VHS-1) se ha detectado en líquido cefalorraquídeo y en sangre periférica de pacientes con esclerosis múltiple durante recaídas inflamatorias, así como también en mayor frecuencia en muestras de cerebro post muerte de individuos con esclerosis múltiple que en individuos sanos. Además, las infecciones producidas por VHS-1 son principalmente asintomáticas y este virus podría alcanzar el cerebro a lo largo de la vida sin síntomas clínicos evidentes. Además, datos acumulados sugieren que la infección persistente con VHS-1 en el cerebro produce prolongada neuroinflamación debido a continuas reactivaciones subclínicas que conduce a desordenes neurodegenerativos en personas susceptibles. El objetivo de esta tesis fue determinar si la infección asintomática con VHS-1 favorece el inicio de la esclerosis múltiple y su severidad. Nosotros abordamos esta pregunta usando animales que recapitulan varios aspectos relacionados con la enfermedad de la esclerosis múltiple y la infección con VHS-1 en humanos. Primero, infectamos ratones con una dosis no letal de VHS-1, esperamos a la recuperación de la infección aguda, al menos 30 días, y luego inducimos la enfermedad de encefalomielitis autoinmune experimental (EAE), la cual es el principal modelo animal usado para estudiar la enfermedad de esclerosis múltiple. El inicio y severidad de síntomas de esclerosis múltiple en el modelo murino de EAE fue comparado con animales no infectados. Determinamos las poblaciones de células inmunes infiltrando SNC de ratones después de la infección con VHS-1 e inducción de EAE, así como también las citoquinas producidas en este tejido luego del inicio de la autoinmunidad. También evaluamos la permeabilidad de la barrera hemato-encefálica 30 días post infección con VHS-1. Nuestros resultados muestran que una infección previa con VHS-1 acelera el inicio de EAE y aumenta la severidad de la enfermedad en el modelo murino. Además, animales previamente infectados con VHS-1 e inducidos a desarrollar EAE padecen una mayor inflamación de SNC que los animales no infectados, lo cual se caracterizó por prolongada activación de microglía, una elevada infiltración de células T CD4+ en el cerebro y neutrófilos en la médula espinal, y niveles de expresión significativos de mRNA de las citoquinas IL-6 e IL-1β en estos tejidos. Notablemente, también encontramos que después de la infección asintomática con VHS-1, la barrera hematoencefálica permanece alterada hasta por 30 días cuando no son detectados viriones. Esperamos que este estudio ayude a definir mejor la posible contribución de la infección por VHS-1 en la enfermedad de la esclerosis múltiple y a garantizar futuros estudios y ensayos con intervenciones antivirales como un potencial tratamiento de esta enfermedad para retardar su progresión.
- ItemExperimental Dissection of the Lytic Replication Cycles of Herpes Simplex Viruses in vitro(2018) Ibáñez Irribarra, Francisco Javier; Farías León, Mónica Andrea; González Troncoso Mp; Corrales N.; Duarte Peñaloza, Luisa Fernanda; Retamal Díaz, Angello Ricardo; González Muñoz, Pablo Alberto
- ItemHeme Oxygenase-1 Expression in Dendritic Cells Contributes to Protective Immunity against Herpes Simplex Virus Skin Infection(MDPI, 2023) Tognarelli Torres, Eduardo Ignacio; Duarte Peñaloza, Luisa Fernanda; Farías León, Mónica Andrea; Cancino Prado, Felipe Andrés; Corrales Bonilla, Nicolas; Ibañez Irribarra, Francisco Javier; Riedel Soria, Claudia; Bueno Ramírez, Susan; Kalergis Parra,Alexis Mikes; González Muñoz, Pablo AlbertoHerpes 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.
- ItemHerpes Simplex Virus Type 1 Infection of the Central Nervous System : Insights Into Proposed Interrelationships With Neurodegenerative Disorders(2019) Duarte Peñaloza, Luisa Fernanda; Farías León, Mónica Andrea; Álvarez Espejo, Diana Claudia Marcela; Bueno Ramírez, Susan; Riedel Soria, Claudia; González Muñoz, Pablo Alberto; Gonzalez-Dunia, DanielHerpes simplex virus type 1 (HSV-1) is highly prevalent in humans and can reach the brain without evident clinical symptoms. Once in the central nervous system (CNS), the virus can either reside in a quiescent latent state in this tissue, or eventually actively lead to severe acute necrotizing encephalitis, which is characterized by exacerbated neuroinflammation and prolonged neuroimmune activation producing a life-threatening disease. Although HSV-1 encephalitis can be treated with antivirals that limit virus replication, neurological sequelae are common and the virus will nevertheless remain for life in the neural tissue. Importantly, there is accumulating evidence that suggests that HSV-1 infection of the brain both, in symptomatic and asymptomatic individuals could lead to neuronal damage and eventually, neurodegenerative disorders. Here, we review and discuss acute and chronic infection of particular brain regions by HSV-1 and how this may affect neuron and cognitive functions in the host. We review potential cellular and molecular mechanisms leading to neurodegeneration, such as protein aggregation, dysregulation of autophagy, oxidative cell damage and apoptosis, among others. Furthermore, we discuss the impact of HSV-1 infection on brain inflammation and its potential relationship with neurodegenerative diseases.
- ItemInterim report: Safety and immunogenicity of an inactivated vaccine against SARS-CoV-2 in healthy chilean adults in a phase 3 clinical trial(2021) Bueno Ramírez, Susan; Abarca Villaseca, Katia; González Adonis, Pablo Andrés; Gálvez Arriagada, Nicolás Marcelo Salvador; Soto Ramírez, Jorge Andrés; Duarte Peñaloza, Luisa Fernanda; Schultz Lombardic, Bárbara M.; Pacheco, Gaspar A.; González Carreño, Liliana Andrea; Vázquez, Yaneisi; Ríos Raggio, Mariana; Melo González, Felipe; Rivera Pérez, Daniela; Iturriaga, Carolina; Urzúa Acevedo, Marcela del Pilar; Domínguez De Landa, María Angélica; Andrade Parra, Catalina Andrea; Berríos Rojas, Roslye; Canedo Marroquín, Giselda; Covián, CamilaThe ongoing COVID-19 pandemic has had a significant impact worldwide, with an incommensurable social and economic burden. The rapid development of safe and protective vaccines against this disease is a global priority. CoronaVac is a vaccine prototype based on inactivated SARS-CoV-2, which has shown promising safety and immunogenicity profiles in pre-clinical studies and phase 1/2 trials in China. To this day, four phase 3 clinical trials are ongoing with CoronaVac in Brazil, Indonesia, Turkey, and Chile. This article reports the safety and immunogenicity results obtained in a subgroup of participants aged 18 years and older enrolled in the phase 3 Clinical Trial held in Chile.