Browsing by Author "Barrera, Aldo"

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    Kinetic of humoral response induced by SARS-CoV-2 infection in convalescent plasma receptors and donors
    (WILEY, 2021) Barrera, Aldo; Martinez Valdebenito, Constanza; Rojas Orellana, Luis; Vizcaya Altamirano, Cecilia; Elena Ceballos, Maria; Pereira, Jaime; Chang, Mayling; Mondaca, Sebastian; Sarmiento, Mauricio; Ross, Patricio; Henriquez, Carolina; Nervi, Bruno; Ferres, Marcela; Balcells, Elvira; Le Corre, Nicole
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    LDL particle size and antioxidant HDL function improve after sustained virological response in patients with chronic HCV
    (2022) Ignacio Vargas, Jose; Rivera, Katherine; Arrese, Marco; Benitez, Carlos; Barrera, Francisco; Hugo, Monrroy; Pablo Arab, Juan; Pino, Karla; Barrera, Aldo; Lopez-Lastra, Marcelo; Rigotti, Attilio; Soza, Alejandro
    HCV infection is associated with an increased incidence of cardiovascular (CV) events. Mechanisms underlying this association remain unknown. In our study, twenty HCV patients (median age 60.5 years, 65% male and 80% with cirrhosis) were evaluated prior, during and after direct-acting antiviral treatment. Ninety percent of patients achieved sustained virological response (SVR). Significant changes were observed in LDL particle size index, measured by LDL-C/apoB ratio, which increased after treatment (p = 0.023). In addition, HDL antioxidant capacity improved gradually from 34.4% at baseline to 42.4% at 4 weeks (p = 0.011), 65.9% at end of treatment EOT (p = 0.002) and remained elevated at 12-week (p = 0.001) after EOT compared to baseline values. Our findings suggest that a shift to a less atherogenic lipid profile may be a possible mechanism associated with CV risk reduction in patients with HCV infection achieving SVR. (c) 2021 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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    Post-translational modifications of hnRNP A1 differentially modulate retroviral IRES-mediated translation initiation
    (2020) Barrera, Aldo; Ramos, Hade; Vera-Otarola, Jorge; Fernandez-Garcia, Leandro; Angulo, Jenniffer; Olguin, Valeria; Pino, Karla; Mouland, Andrew J.; Lopez-Lastra, Marcelo
    The full-length mRNAs of the human immunodeficiency virus type-1 (HIV-1), the human T-cell lymphotropic virus type-1 (HTLV-1), and the mouse mammary tumor virus (MMTV) harbor IRESs. The activity of the retroviral-IRESs requires IRES-transacting factors (ITAFs), being hnRNP A1, a known ITAF for the HIV-1 IRES. In this study, we show that hnRNP A1 is also an ITAF for the HTLV-1 and MMTV IRESs. The MMTV IRES proved to be more responsive to hnRNP A1 than either the HTLV-1 or the HIV-1 IRESs. The impact of post-translational modifications of hnRNP A1 on HIV-1, HTLV-1 and MMTV IRES activity was also assessed. Results show that the HIV-1 and HTLV-1 IRESs were equally responsive to hnRNP A1 and its phosphorylation mutants S4A/S6A, S4D/S6D and S199A/D. However, the S4D/S6D mutant stimulated the activity from the MMTV-IRES to levels significantly higher than the wild type hnRNP A1. PRMT5-induced symmetrical di-methylation of arginine residues of hnRNP A1 enabled the ITAF to stimulate the HIV-1 and HTLV-1 IRESs while reducing the stimulatory ability of the ITAF over the MMTV IRES. We conclude that retroviral IRES activity is not only dependent on the recruited ITAFs but also relies on how these proteins are modified at the post-translational level.
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    SARS-CoV-2 infectivity and antigenic evasion: spotlight on isolated Omicron sub-lineages
    (2024) Barrera, Aldo; Martinez-Valdebenito, Constanza; Angulo, Jenniffer; Palma, Carlos; Hormazabal, Juan; Vial, Cecilia; Aguilera, Ximena; Castillo-Torres, Pablo; Pardo-Roa, Catalina; Balcells, Maria Elvira; Nervi, Bruno; Le Corre, Nicole; Ferres, Marcela
    Since the SARS-CoV-2 outbreak in 2019, a diversity of viral genomic variants has emerged and spread globally due to increased transmissibility, pathogenicity, and immune evasion. By the first trimester of 2023 in Chile, as in most countries, BQ and XBB were the predominant circulating sub-lineages of Omicron. The molecular and antigenic characteristics of these variants have been mainly determined using non-authentic spike pseudoviruses, which is often described as a limitation. Additionally, few comparative studies using isolates from recent Omicron sub-lineages have been conducted. In this study, we isolated SARS-CoV-2 variants from clinical samples, including the ancestral B.1.1, Delta, Omicron BA.1, and sub-lineages of BA.2 and BA.5. We assessed their infectivity through cell culture infections and their antibody evasion using neutralization assays. We observed variations in viral plaque size, cell morphology, and cytotoxicity upon infection in Vero E6-TMPRSS2 cells for each variant compared to the ancestral B.1.1 virus. BA.2-derived sub-variants, such as XBB.1.5, showed attenuated viral replication, while BA.5-derived variants, such as BQ.1.1, exhibited replication rates similar to the ancestral SARS-CoV-2 virus. Similar trends were observed in intestinal Caco-2 cells, except for Delta. Antibody neutralization experiments using sera from individuals infected during the first COVID-19 wave (FWI) showed a consistent but moderate reduction in neutralization against Omicron sub-lineages. Interestingly, despite being less prevalent, BQ.1.1 showed a 6.1-fold greater escape from neutralization than XBB.1.5. Neutralization patterns were similar when tested against sera from individuals vaccinated with 3xBNT162b2 (PPP) or Coronavac-Coronavac-BNT162b2 (CCP) schedules. However, CCP sera showed 2.3-fold higher neutralization against XBB.1.5 than FWI and PPP sera. This study provides new insights into the differences between BA.2 and BA.5-derived variants, leading to their eventual outcompetition. Our analysis offers important evidence regarding the balance between infectivity and antigenic escape that drives the evolution of second-generation SARS-CoV-2 variants in the population.
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    The double-stranded RNA-binding protein, Staufen1 is an IRES-transacting factor regulating HIV-1 cap-independent translation initiation
    (2022) Ramos, Hade; Monette, Anne; Niu, Meijuan; Barrera, Aldo; Lopez-Ulloa, Brenda; Fuentes, Yazmin; Guizar, Paola; Pino, Karla; DesGroseillers, Luc; Mouland, Andrew J.; Lopez-Lastra, Marcelo
    Translation initiation of the viral genomic mRNA (vRNA) of human immunodeficiency virus-type 1 (HIV-1) can be mediated by a cap- or an internal ribosome entry site (IRES)-dependent mechanism. A previous report shows that Staufen1, a cellular double-stranded (ds) RNA-binding protein (RBP), binds to the 5'untranslated region (5'UTR) of the HIV-1 vRNA and promotes its cap-dependent translation. In this study, we now evaluate the role of Staufen1 as an HIV-1 IRES-transacting factor (ITAF). We first confirm that Staufen1 associates with both the HIV-1 vRNA and the Gag protein during HIV-1 replication. We found that in HIV-1-expressing cells, siRNA-mediated depletion of Staufen1 reduces HIV-1 vRNA translation. Using dual-luciferase bicistronic mRNAs, we show that the siRNA-mediated depletion and cDNA-mediated overexpression of Staufen1 acutely regulates HIV-1 IRES activity. Furthermore, we show that Staufenl-vRNA interaction is required for the enhancement of HIV-1 IRES activity. Interestingly, we find that only Staufen1 harboring an intact dsRNA-binding domain 3 (dsRBD3) rescues HIV-1 IRES activity in Staufen1 CRISPR-Cas9 gene edited cells. Finally, we show that the expression of Staufen1-dsRBD3 alone enhances HIV-1 IRES activity. This study provides evidence of a novel role for Staufen1 as an ITAF promoting HIV-1 vRNA IRES activity.
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    The Internal Ribosome Entry Site of Dengue Virus mRNA Is Active When Cap-Dependent Translation Initiation Is Inhibited
    (2021) Fernandez-Garcia, Leandro; Angulo, Jenniffer; Ramos, Hade; Barrera, Aldo; Pino, Karla; Vera-Otarola, Jorge; Lopez-Lastra, Marcelo
    Dengue virus (DENV) is an enveloped, positive-sense, single-stranded RNA virus belonging to the Flaviviridae family. Translation initiation of DENV mRNA can occur by a cap-dependent or a cap-independent mechanism. Two non-mutually exclusive cap-independent mechanisms of translation initiation have been described for DENV mRNA. The first corresponds to a 5'-end-dependent, internal ribosome entry site (IRES)-independent mechanism, while the second relies on IRES-dependent initiation. In this report, we study the recently discovered DENV IRES. The results show that the DENV IRES is functional in the rabbit reticulocyte lysate (RRL). In accordance, the activity of the DENV IRES was resistant to the cleavage of eukaryotic initiation factor 4G (eIF4G) by the Foot-and-mouth disease virus leader protease in RRL In cells, the DENV IRES exhibited only marginal activity under standard culture conditions. The DENV IRES showed weak activity in HEK 293T cells; however, DEW IRES activity was significantly enhanced in HEK 293T cells expressing Human rhinovirus 2A protease. These findings suggest that the DENV IRES enables viral protein synthesis under conditions that suppress canonical translation initiation.
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    Viral shedding and viraemia of Andes virus during acute hantavirus infection: a prospective study
    (2024) Ferres, Marcela; Martinez-Valdebenito, Constanza; Henriquez, Carolina; Marco, Claudia; Angulo, Jenniffer; Barrera, Aldo; Palma, Carlos; Pinto, Gonzalo Barriga; Cuiza, Analia; Ferreira, Leonila; Rioseco, Maria Luisa; Calvo, Mario; Fritz, Ricardo; Bravo, Sebastian; Bruhn, Alejandro; Graf, Jeronimo; Llancaqueo, Alvaro; Rivera, Gonzalo; Cerda, Carolina; Tischler, Nicole; Valdivieso, Francisca; Vial, Pablo; Mertz, Gregory; Vial, Cecilia; Le Corre, Nicole
    Background Andes virus (ANDV) is a zoonotic Orthohantavirus leading to hantavirus cardiopulmonary syndrome. Although most transmissions occur through environmental exposure to rodent faeces and urine, rare person -toperson transmission has been documented, mainly for close contacts. This study investigates the presence and infectivity of ANDV in body fluids from confirmed cases and the duration of viraemia. Methods In this prospective study, 131 participants with confirmed ANDV infection were enrolled in Chile in a prospective study between 2008 and 2022. Clinical samples (buffy coat, plasma, gingival crevicular fluid [GCF], saliva, nasopharyngeal swabs [NPS], and urine) were collected weekly for 3 weeks together with clinical and epidemiological data. Samples were categorised as acute or convalescent (up to and after 16 days following onset of symptoms). Infectivity of positive fluids was assessed after the culture of samples on Vero E6 cells and use of flow cytometry assays to determine the production of ANDV nucleoprotein. Findings ANDV RNA was detected in 100% of buffy coats during acute phase, declining to 95% by day 17, and to 93% between days 23-29. ANDV RNA in GCF and saliva decreased from 30% and 12%, respectively, during the acute phase, to 12% and 11% during the convalescent phase. Successful infectivity assays of RT-qPCR-positive fluids, including GCF, saliva, NPS, and urine, were observed in 18 (42%) of 43 samples obtained during the acute phase of infection. After re -culture, the capacity to infect Vero E6 cells was maintained in 16 (89%) of 18 samples. Severity was associated with the presence of ANDV RNA in one or more fluids besides blood (odds ratio 258 [95% CI 142-518]). Interpretation ANDV infection is a systemic and viraemic infection, that affects various organs. The presence of infectious particles in body fluids contributes to our understanding of potential mechanisms for person -to -person transmission, supporting the development of preventive strategies. Detection of ANDV RNA in additional fluids at hospital admission is a predictor of disease severity. Funding National Institutes of Health and Agencia de Investigaci & oacute;n y Desarrollo. Copyright (c) 2024 Elsevier Ltd. All rights reserved.