Browsing by Author "Pardo-Roa, Catalina"

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    Assessment of Mutations Associated With Genomic Variants of SARS-CoV-2: RT-qPCR as a Rapid and Affordable Tool to Monitoring Known Circulating Variants in Chile, 2021
    (SPRINGER INTERNATIONAL PUBLISHING AG, 2022) Angulo, Jenniffer; Martinez-Valdebenito, Constanza; Pardo-Roa, Catalina; Almonacid, Leonardo I. I.; Fuentes-Luppichini, Eugenia; Contreras, Ana Maria; Maldonado, Constanza; Le Corre, Nicole; Melo, Francisco; Medina, Rafael A. A.; Ferres, Marcela
    Since the first report of SARS-CoV-2 infection in humans, the virus has mutated to develop new viral variants with higher infection rates and more resistance to neutralization by antibodies elicited after natural SARS-CoV-2 infection or by vaccines. Therefore, rapid identification of viral variants circulating in the population is crucial for epidemiological assessment and efforts to contain the resurgence of the pandemic. Between January and November 2021, we performed a large variant RT-qPCR-based screening of mutations in the spike protein of 1851 SARS-CoV-2-positive samples derived from outpatients from the UC-Christus Health Network in Chile. In a portion of samples (n = 636), we validated our RT-qPCR-pipeline by WGS, obtaining a 99.2% concordance. Our results indicate that from January to March 2021 there was a dominance of non-identifiable variants by the RT-qPCR-based screening; however, throughout WGS we were able to identify the Lambda (C.37) variant of interest (VOI). From March to July, we observed the rapid emergence of mutations associated with the Gamma variant (P.1), which was quickly replaced by the appearance of a combination of samples harboring mutations associated with the Delta variant (B.1.617.2), which predominated until the end of the study. Our results highlight the applicability of cost-effective RT-qPCR-based screening of mutations associated with known variants of concern (VOC), VOI and variants under monitoring (VUM) of SARS-CoV-2, being a rapid and reliable tool that complements WGS-based surveillance.
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    Emergence and rapid dissemination of highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b in wild birds, Chile.
    (SPRINGER INTERNATIONAL PUBLISHING AG, 2023) Ariyama, Naomi; Pardo-Roa, Catalina; Munoz, Gabriela; Aguayo, Carolina; Avila, Claudia; Mathieu, Christian; Brito, Barbara; Medina, Rafael; Johow, Magdalena; Neira, Victor
    In December 2022, HPAI H5N1 clade 2.3.4.4b emerged in Chile. We detected the virus in 93 wild bird samples and sequenced the whole genome of nine Chilean strains from pelicans and gulls. Phylogenetic analysis suggests at least two different HPAI viral clusters in South America.
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    First report and genetic characterization of Seneca Valley virus (SVV) in Chile
    (SPRINGER INTERNATIONAL PUBLISHING AG, 2022) Bennett, Benjamin; Urzua-Encina, Constanza; Pardo-Roa, Catalina; Ariyama, Naomi; Lecocq, Claudio; Rivera, Carlos; Badia, Catalina; Suarez, Paulina; Agredo, Michel; Aguayo, Carolina; Avila, Claudia; Araya, Hugo; Perez, Patricio; Berrios, Felipe; Aguero, Belen; Mendieta, Vanessa; Pituco, Edviges Maristela; de Almeida, Iassudara Garcia; Medina, Rafael; Brito, Barbara; Johow, Magdalena; Neira Ramirez, Victor
    Seneca Valley virus (SVV) is a non-enveloped RNA virus and the only member of the Senecavirus A (SVA) species, in the Senecavirus genus, Picornaviridae family. SVV infection causes vesicular lesions in the oral cavity, snout and hooves of pigs. This infection is clinically indistinguishable from trade-restrictions-related diseases such as foot-and-mouth disease. Other clinical manifestations include diarrhoea, anorexia, lethargy, neurological signs and mortality in piglets during their first week of age. Before this study, Chile was considered free of vesicular diseases of swine, including SVV. In April 2022, a suspected case of vesicular disease in a swine farm was reported in Chile. The SVV was confirmed and other vesicular diseases were ruled out. An epidemiological investigation and phylogenetic analyses were performed to identify the origin and extent of the outbreak. Three hundred ninety-five samples from 44 swine farms were collected, including faeces (208), oral fluid (28), processing fluid (14), fresh semen (61), environmental samples (80) and tissue from lesions (4) for real-time RT-PCR detection. Until June 2022, the SVV has been detected in 16 out of 44 farms, all epidemiologically related to the index farm. The closest phylogenetic relationship of the Chilean SVV strain is with viruses collected from swine in California in 2017. The direct cause of the SVV introduction has not yet been identified; however, the phylogenetic analyses suggest the USA as the most likely source. Since the virus remains active in the environment, transmission by fomites such as contaminated feed cannot be discarded. Further studies are needed to determine the risk of the introduction of novel SVV and other transboundary swine pathogens to Chile.
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    Induction of SARS-CoV-2 neutralizing antibodies by CoronaVac and BNT162b2 vaccines in naive and previously infected individuals
    (2022) Muena, Nicolas A.; Garcia-Salum, Tamara; Pardo-Roa, Catalina; Jose Avendano, Maria; Serrano, Eileen F.; Levican, Jorge; Almonacid, Leonardo, I; Valenzuela, Gonzalo; Poblete, Estefany; Strohmeier, Shirin; Salinas, Erick; Munoz, Andres; Haslwanter, Denise; Dieterle, Maria Eugenia; Jangra, Rohit K.; Chandran, Kartik; Gonzalez, Claudia; Riquelme, Arnoldo; Krammer, Florian; Tischler, Nicole D.; Medina, Rafael A.
    Interpretation The decay of nAbs titres in previously infected individuals over time indicates that vaccination is needed to boost humoral memory responses. Immunization of naydve individuals with two doses of CoronaVac induced nAbs titres that were significantly lower to that of convalescent patients, and similar to vaccination with one dose of BTN162b2. The real life effectiveness for CoronaVac in Chile was higher than estimated; indicating that lower titres and additional cellular immune responses induced by CoronaVac might afford protection in a highly immunized population. Nevertheless, the lower nAb titre induced by two doses of CoronaVac as compared to the BTN162b2 vaccine in naydve individuals, highlights the need of booster immunizations over time to maintain protec-tive levels of antibody, particularly with the emergence of new SARS-CoV-2 variants. Funding FONDECYT 1161971, 1212023, 1181799, FONDECYT Postdoctorado 3190706 and 3190648, ANID Becas/ Doctorado Nacional 21212258, PIA ACT 1408, CONICYT REDES180170, Centro Ciencia & Vida, FB210008, Finan-ciamiento Basal para Centros Cient?ficos y Tecnol?ogicos de Excelencia grants from the Agencia Nacional de Inves-tigaci?on y Desarrollo (ANID) of Chile; NIH-NIAD grants U19AI135972, R01AI132633 and contracts HHSN272201400008C and 75N93019C00051; the JPB Foundation, the Open Philanthropy Project grant 2020-215611 (5384); and by anonymous donors. The funders had no role in study design, data collection and analysis, deci-sion to publish, or preparation of the manuscript. Copyright (c) 2022 The Authors. Published by Elsevier B.V. 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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    Limited Heme Oxygenase Contribution to Modulating the Severity of Salmonella enterica serovar Typhimurium Infection
    (SPRINGER INTERNATIONAL PUBLISHING AG, 2022) Sebastian, Valentina P.; Moreno-Tapia, Daniela; Melo-Gonzalez, Felipe; Hernandez-Caceres, Maria P.; Salazar, Geraldyne A.; Pardo-Roa, Catalina; Farias, Monica A.; Vallejos, Omar P.; Schultz, Barbara M.; Morselli, Eugenia; Alvarez-Lobos, Manuel M.; Gonzalez, Pablo A.; Kalergis, Alexis M.; Bueno, Susan M.
    An important virulence trait of Salmonella enterica serovar Typhimurium (S. Typhimurium) is the ability to avoid the host immune response, generating systemic and persistent infections. Host cells play a crucial role in bacterial clearance by expressing the enzyme heme oxygenase 1 (Hmox1), which catalyzes the degradation of heme groups into Fe2+, biliverdin, and carbon monoxide (CO). The role of Hmox1 activity during S. Typhimurium infection is not clear and previous studies have shown contradictory results. We evaluated the effect of pharmacologic modulation of Hmox1 in a mouse model of acute and persistent S. Typhimurium infection by administering the Hmox1 activity inductor cobalt protoporphyrin-IX (CoPP) or inhibitor tin protoporphyrin-IX (SnPP) before infection. To evaluate the molecular mechanism involved, we measured the colocalization of S. Typhimurium and autophagosome and lysosomal markers in macrophages. Administering CoPP reduced the bacterial burden in organs of mice 5 days post-infection, while SnPP-treated mice showed bacterial loads similar to vehicle-treated mice. Furthermore, CoPP reduced bacterial loads when administered after infection in macrophages in vitro and in a persistent infection model of S. Typhimurium in vivo, while tin protoporphyrin-IX (SnPP) treatment resulted in a bacterial burden similar to vehicle-treated controls. However, we did not observe significant differences in co-localization of green fluorescent protein (GFP)-labeled S. Typhimurium with the autophagic vesicles marker microtubule-associated protein 1A/1B-light chain 3 (LC3) and the lysosomal marker lysosomal-associated membrane protein 1 (LAMP-1) in macrophages treated with CoPP. Our results suggest that CoPP can enhance antimicrobial activity in response to Salmonella infection, reducing bacterial dissemination and persistence in mice, in a CO and autophagy- independent manner.
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    Omicron variant Spike-specific antibody binding and Fc activity are preserved in recipients of mRNA or inactivated COVID-19 vaccines
    (2022) Bartsch, Yannic C.; Tong, Xin; Kang, Jaewon; Avendano, Maria Jose; Serrano, Eileen F.; Garcia-Salum, Tamara; Pardo-Roa, Catalina; Riquelme, Arnoldo; Cai, Yongfei; Renzi, Isabella; Stewart-Jones, Guillaume; Chen, Bing; Medina, Rafael A.; Alter, Galit
    The Omicron variant of SARS-CoV-2 has been shown to evade neutralizing antibodies elicited by vaccination or infection. Despite the global spread of the Omicron variant, even among highly vaccinated populations, death rates have not increased concomitantly. These data suggest that immune mechanisms beyond antibody-mediated virus neutralization may protect against severe disease. In addition to neutralizing pathogens, antibodies contribute to control and clearance of infections through Fc effector mechanisms. Here, we probed the ability of vaccine-induced antibodies to drive Fc effector activity against the Omicron variant using samples from individuals receiving one of three SARS-CoV-2 vaccines. Despite a substantial loss of IgM, IgA, and IgG binding to the Omicron variant receptor binding domain (RBD) in samples from individuals receiving BNT162b2, mRNA-1273, and CoronaVac vaccines, stable binding was maintained against the full-length Omicron Spike protein. Compromised RBD binding IgG was accompanied by a loss of RBD-specific antibody Fc gamma receptor (Fe gamma R) binding in samples from individuals who received the CoronaVac vaccine, but RBD-specific Fc gamma R2a and Fc gamma R3a binding was preserved in recipients of mRNA vaccines. Conversely, Spike protein-specific antibodies exhibited persistent but reduced binding to Fc gamma Rs across all three vaccines, although higher binding was observed in samples from recipients of mRNA vaccines. This was associated with preservation of Fc gamma R2a and Fc gamma R3a binding antibodies and maintenance of Spike protein-specific antibody-dependent natural killer cell activation. Thus, despite the loss of Omicron neutralization, vaccine-induced Spike protein-specific antibodies continue to drive Fc effector functions, suggesting a capacity for extraneutralizing antibodies to contribute to disease control.