Browsing by Author "Angulo, Jenniffer"
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Item A Single-Nucleotide Polymorphism of αVβ3 Integrin Is Associated with the Andes Virus Infection Susceptibility(2019) Martínez-Valdebenito, Constanza; Angulo, Jenniffer; Corre, Nicole Le; Marco, Claudia; Vial, Cecilia; Miquel, Juan Francisco; Cerda, Jaime; Mertz, Gregory; Vial, Pablo; Lopez-Lastra, Marcelo; Ferrés, MarcelaThe Andes Orthohantavirus (ANDV), which causes the hantavirus cardiopulmonary syndrome, enters cells via integrins, and a change from leucine to proline at residue 33 in the PSI domain (L33P), impairs ANDV recognition. We assessed the association between this human polymorphism and ANDV infection. We defined susceptible and protective genotypes as “TT” (coding leucine) and “CC” (coding proline), respectively. TT was present at a rate of 89.2% (66/74) among the first cohort of ANDV cases and at 60% (63/105) among exposed close-household contacts, who remained uninfected (p < 0.05). The protective genotype (CC) was absent in all 85 ANDV cases, in both cohorts, and was present at 11.4% of the exposed close-household contacts who remained uninfected. Logistic regression modeling for risk of infection had an OR of 6.2–12.6 (p < 0.05) in the presence of TT and well-known ANDV risk activities. Moreover, an OR of 7.3 was obtained when the TT condition was analyzed for two groups exposed to the same environmental risk. Host genetic background was found to have an important role in ANDV infection susceptibility, in the studied population.Item Molecular Description of a Novel Orientia Species Causing Scrub Typhus in Chile(2020-09) Abarca, Katia; Martínez-Valdebenito, Constanza; Angulo, Jenniffer; Jiang, Ju; Farris, Christina M.; Richards, Allen L.; Acosta-Jamett, Gerardo; Weitzel, ThomasScrub typhus is a potentially fatal rickettsiosis caused by Orientia species intracellular bacteria of the genus Orientia. Although considered to be restricted to the Asia Pacific region, scrub typhus has recently been discovered in southern Chile. We analyzed Orientia gene sequences of 16S rRNA (rrs) and 47-kDa (htrA) from 18 scrub typhus patients from Chile. Sequences were ≥99.7% identical among the samples for both amplified genes. Their diversity was 3.1%–3.5% for rrs and 11.2%–11.8% for htrA compared with O. tsusugamushi and 3.0% for rrs and 14.8% for htrA compared with Candidatus Orientia chuto. Phylogenetic analyses of both genes grouped the specimens from Chile in a different clade from other Orientia species. Our results indicate that Orientia isolates from Chile constitute a novel species, which, until they are cultivated and fully characterized, we propose to designate as Candidatus Orientia chiloensis, after the Chiloé Archipelago where the pathogen was identified.Item Mother-to-Child Transmission of Andes Virus through Breast Milk, Chile(2020-08) Ferrés, Marcela; Martínez-Valdebenito, Constanza; Angulo, Jenniffer; Henríquez, Carolina; Vera-Otaróla, Jorge; Vergara, María José; Pérez, Javier; Fernández, Jorge; Sotomayor, Viviana; Valdés, María Francisca; González-Candia, Diego; Tischler, Nicole D.; Vial, Cecilia; Vial, Pablo; Mertz, Gregory; Le Corre, NicoleAndes virus (ANDV) is the only hantavirus transmitted between humans through close contact. We detected the genome and proteins of ANDV in breast milk cells from an infected mother in Chile who transmitted the virus to her child, suggesting gastrointestinal infection through breast milk as a route of ANDV person-to-person transmission.Publication SARS-CoV-2 infectivity and antigenic evasion: spotlight on isolated Omicron sub-lineages(2024) Barrera, Aldo; Martínez, Constanza; Angulo, Jenniffer; Palma, Carlos; Hormazabal, Juan; Vial Cox, María Cecilia; Aguilera, Ximena; Castillo, Pablo; Pardo, Catalina; Balcells, María; Nervi, Bruno; Le Corre, Nicole; Ferrés, MarcelaSince 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.