Browsing by Author "Soto Rifo, Ricardo"

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    Early versus deferred anti-SARS-CoV-2 convalescent plasma in patients admitted for COVID-19: A randomized phase II clinical trial
    (2021) Balcells Marty, Maria Elvira; Rojas Orellana, Luis Esteban; Martínez Valdebenito, Constanza Pamela; Ceballos Valdivielso, María Elena Andrea; Ferrés Garrido, Marcela Viviana; Chang Rathkamp, Mayling Raquel; Vizcaya Altamirano, María Cecilia; Mondaca Contreras, Sebastián Patricio; Huete Garín, Isidro Álvaro; Castro López, Ricardo Adolfo; Sarmiento Maldonado, Mauricio; Villarroel Del Pino, Luis Antonio; Pizarro Ibáñez, Alejandra Valentina; Ross Pérez, Patricio Daniel; Santander Toro, Jaime Andrés; Lara Hernández, Bárbara Alejandra; Ferrada Koch, Marcela Patricia; Vargas Salas, Sergio Sebastián; Beltrán Pávez, Carolina; Soto Rifo, Ricardo; Valiente Echeverria, Fernando Andrés; Caglevic, Christian; Mahave, Mauricio; Selman Bravo, Carolina Antoniett; Gazitúa, Raimundo; Briones, José Luis; Villarroel Espíndola, Franz; Balmaceda Araque, Carlos Felipe; Espinoza Sepúlveda, Manuel Antonio; Pereira Garces, Jaime; Nervi Nattero, Bruno; Le Corre Perez, Monique Nicole
    Background: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression.", "Methods and findings", "The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32-2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19-2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion.", "Conclusions", "In the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration.
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    Immune responses during COVID-19 breakthrough cases in vaccinated children and adolescents
    (Frontiers Media SA, 2024) Rivera Pérez, Daniela; Méndez Vejar, Constanza Soledad; Diethelm Varela, Benjamín Manuel; Melo González, Felipe Andrés; Vázquez Hernández, Yaneisi; Meng, Xing; Xin, Qianqian; Fasce, Rodrigo A.; Fernández, Jorge; Mora, Judith; Ramírez, Eugenio; Acevedo, Mónica L.; Valiente Echeverria, Fernando; Soto Rifo, Ricardo; Grifoni, Alba; Weiskopf, Daniela; Sette, Alessandro; Astudillo Paredes, Patricio Andrés; Le Corre Pérez, Monique Nicole; Abarca Villaseca, Katia; Perret Pérez, Cecilia; González Muñoz, Pablo Alberto; Soto Ramírez, Jorge Andrés; Bueno Ramírez, Susan; Kalergis, Alexis M.
    Background: Vaccine effectiveness against SARS-CoV-2 infection has been somewhat limited due to the widespread dissemination of the Omicron variant, its subvariants, and the immune response dynamics of the naturally infected with the virus. Methods: Twelve subjects between 3-17 years old (yo), vaccinated with two doses of CoronaVac®, were followed and diagnosed as breakthrough cases starting 14 days after receiving the second dose. Total IgGs against different SARS-CoV-2 proteins and the neutralizing capacity of these antibodies after infection were measured in plasma. The activation of CD4+ and CD8+ T cells was evaluated in peripheral blood mononuclear cells stimulated with peptides derived from the proteins from the wild-type (WT) virus and Omicron subvariants by flow cytometry, as well as different cytokines secretion by a Multiplex assay. Results: 2 to 8 weeks post-infection, compared to 4 weeks after 2nd dose of vaccine, there was a 146.5-fold increase in neutralizing antibody titers against Omicron and a 38.7-fold increase against WT SARS-CoV-2. Subjects showed an increase in total IgG levels against the S1, N, M, and NSP8 proteins of the WT virus. Activated CD4+ T cells showed a significant increase in response to the BA.2 subvariant (p<0.001). Finally, the secretion of IL-2 and IFN-γ cytokines showed a discreet decrease trend after infection in some subjects. Conclusion: SARS-CoV-2 infection in the pediatric population vaccinated with an inactivated SARS-CoV-2 vaccine produced an increase in neutralizing antibodies against Omicron and increased specific IgG antibodies for different SARS-CoV-2 proteins. CD4+ T cell activation was also increased, suggesting a conserved cellular response against the Omicron subvariants, whereas Th1-type cytokine secretion tended to decrease. Clinical Trial Registration: clinicaltrials.gov #NCT04992260
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    Insights into neutralizing antibody responses in individuals exposed to SARS-CoV-2 in Chile
    (2021) Beltrán Pavez, Carolina; Riquelme Barrios, Sebastián; Oyarzún Arrau, Aarón; Gaete Argel, Aracelly; González Stegmaier, Roxana; Cereceda Solis, Karina; Aguirre, Adam; Travisany, Dante; Palma Vejares, Ricardo; Barriga, Gonzalo P.; Gaggero, Aldo; Martínez Valdebenito, Constanza; Le Corre Pérez, Monique Nicole; Ferrés, Marcela; Balcells Marty, María Elvira; Fernández, Jorge; Ramírez, Eugenio; Villarroel, Franz; Valiente Echeverría, Fernando; Soto Rifo, Ricardo
    Chile has one of the worst numbers worldwide in terms of SARS-CoV-2 positive cases and COVID-19-related deaths per million inhabitants; thus, characterization of neutralizing antibody (NAb) responses in the general population is critical to understanding of immunity at the local level. Given our inability to perform massive classical neutralization assays due to the scarce availability of BSL-3 facilities in the country, we developed and fully characterized an HIV-based SARS-CoV-2 pseudotype, which was used in a 96-well plate format to investigate NAb responses in samples from individuals exposed to SARS-CoV-2 or treated with convalescent plasma. We also identified samples with decreased or enhanced neutralization activity against the D614G spike variant compared with the wild type, indicating the relevance of this variant in host immunity. The data presented here represent the first insights into NAb responses in individuals from Chile, serving as a guide for future studies in the country.
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    Mechanism of HIV-1 Tat RNA translation and its activation by the Tat protein
    (2009) Charnay, Nicolas; López Lastra, Marcelo Andrés; Ivanyi-Nagy, Roland; Soto Rifo, Ricardo; Ohlmann, Théophile; Darlix, Jean-Luc
    Abstract Background The human immunodeficiency virus type 1 (HIV-1) Tat protein is a major viral transactivator required for HIV-1 replication. In the nucleus Tat greatly stimulates the synthesis of full-length transcripts from the HIV-1 promoter by causing efficient transcriptional elongation. Tat induces elongation by directly interacting with the bulge of the transactivation response (TAR) RNA, a hairpin-loop located at the 5'-end of all nascent viral transcripts, and by recruiting cellular transcriptional co-activators. In the cytoplasm, Tat is thought to act as a translational activator of HIV-1 mRNAs. Thus, Tat plays a central role in the regulation of HIV-1 gene expression both at the level of mRNA and protein synthesis. The requirement of Tat in these processes poses an essential question on how sufficient amounts of Tat can be made early on in HIV-1 infected cells to sustain its own synthesis. To address this issue we studied translation of the Tat mRNA in vitro and in human cells using recombinant monocistronic and dicistronic RNAs containing the 5' untranslated region (5'-UTR) of Tat RNA. Results This study shows that the Tat mRNA can be efficiently translated both in vitro and in cells. Furthermore, our data suggest that translation initiation from the Tat mRNA probably occurs by a internal ribosome entry site (IRES) mechanism. Finally, we show that Tat protein can strongly stimulate translation from its cognate mRNA in a TAR dependent fashion. Conclusion These results indicate that Tat mRNA translation is efficient and benefits from a feedback stimulation by the Tat protein. This translational control mechanism would ensure that minute amounts of Tat mRNA are sufficient to generate enough Tat protein required to stimulate HIV-1 replication.
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    The 3 ' Untranslated Region of the Andes Hantavirus Small mRNA Functionally Replaces the Poly(A) Tail and Stimulates Cap-Dependent Translation Initiation from the Viral mRNA
    (AMER SOC MICROBIOLOGY, 2010) Vera Otarola, Jorge; Soto Rifo, Ricardo; Ricci, Emiliano P.; Ohlmann, Theophile; Darlix, Jean Luc; Lopez Lastra, Marcelo
    In the process of translation of eukaryotic mRNAs, the 5' cap and the 3' poly(A) tail interact synergistically to stimulate protein synthesis. Unlike its cellular counterparts, the small mRNA (SmRNA) of Andes hantavirus (ANDV), a member of the Bunyaviridae, lacks a 3' poly(A) tail. Here we report that the 3' untranslated region (3'UTR) of the ANDV SmRNA functionally replaces a poly(A) tail and synergistically stimulates cap-dependent translation initiation from the viral mRNA. Stimulation of translation by the 3'UTR of the ANDV SmRNA was found to be independent of viral proteins and of host poly(A)-binding protein.
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    The Andes Hantavirus NSs Protein Is Expressed from the Viral Small mRNA by a Leaky Scanning Mechanism
    (AMER SOC MICROBIOLOGY, 2012) Vera Otarola, Jorge; Solis, Loretto; Soto Rifo, Ricardo; Ricci, Emiliano P.; Pino, Karla; Tischler, Nicole D.; Ohlmann, Theophile; Darlix, Jean Luc; Lopez Lastra, Marcelo
    The small mRNA (SmRNA) of all Bunyaviridae encodes the nucleocapsid (N) protein. In 4 out of 5 genera in the Bunyaviridae, the smRNA encodes an additional nonstructural protein denominated NSs. In this study, we show that Andes hantavirus (ANDV) SmRNA encodes an NSs protein. Data show that the NSs protein is expressed in the context of an ANDV infection. Additionally, our results suggest that translation initiation from the NSs initiation codon is mediated by ribosomal subunits that have bypassed the upstream N protein initiation codon through a leaky scanning mechanism.
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    Tobacco smoke activates human papillomavirus 16 p97 promoter and cooperates with High-Risk E6/E7 for oxidative DNA damage in lung cells
    (2015) Peña, Nelson; Carrillo, Diego; Muñoz, Juan P.; Chnaiderman, Jonás; Urzúa, Ulises; León, Oscar; Tornesello, María L.; Corvalán R., Alejandro; Soto Rifo, Ricardo; Aguayo González, Francisco
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    Translation initiation is driven by different mechanisms on the HIV-1 and HIV-2 genomic RNAs
    (2013) Breyne, Sylvainde; Soto Rifo, Ricardo; López Lastra, Marcelo Andrés; Ohlmann, Théophile