Role of RNPs and ACDs in HIV-1 replication
Following HIV-1 infection, the host cell responds by mounting a robust, anti-viral immune response in order to create an inhospitable environment for viral replication. During a stress response, cells initiate both the shut-off of protein synthesis and the assembly of stress granules (SG). SG are translationally silent ribonucleoproteins (RNPs) and serve as storage sites of mRNAs and proteins. Importantly, many viruses counter this innate immune response using a variety of strategies. Recent work has revealed that eEF2 depletion impaired the SG blockade mediated by HIV-1 and resulted in decreased virus production and infectivity, we propose that anticancer drugs (ACDs) that promote SG assembly in HIV-1 expressing cells represent an innovative avenue of anti-viral therapeutics
Awakening HIV-1: Reactivation of HIV-1 latency
One of the major challenges for the cure of HIV-1 infection is the persistence of proviral genomes in CD4 + T lymphocytes. Specific approaches are being sought to reverse latency and use immunological mechanisms to eradicate persistent infection. HIV-1 Latency Reversing Agents (LRAs) are small molecules capable of modulating the pathways that control HIV-1 latency and are the first target molecules in this effort. Isoflavonoids represent a class of potentially useful components to counteract HIV-1 infection.
RNAstasis during HIV-1 replication
mRNPs are assembled immediately after the nascent transcript emerges following transcription of DNA and are remodeled by co-transcriptional RNA-processing reactions. After a cellular mRNA reaches the translation machinery, it will undergo degradation as a way of turnover by the mRNA decay machinery. Indeed, it is suggested that mRNA degradation is tightly dependent on translation. As such, mRNA turnover rates also depend on the specific composition of the given mRNPs, cis-acting elements in mRNA and trans-acting factors that contribute to mRNA regulation decay. However, the history is quite different for viruses, which use the same RNA molecule first as mRNA and then as the packaged genome. Thus, it is not surprising that all viruses in general, have evolved different mechanisms aimed to modulate host RNAstasis with a direct impact in the assembly of different RNA granules while counteracting mRNA decay machineries
Current Research Support
Fondo Nacional de Desarrollo Científico y Tecnológico FONDECYT
2023-2027: Fondecyt 1231275
“Unwinding the replicative cycle of the respiratory syncytial virus”
Co-Investigator / PI: M. Acevedo
2023-2027 Fondecyt 1230102
“To be or not to be (sensed): A tale of RNA modifications, RNA-binding proteins, and inflammation during HIV-1 replication in the central nervous system”
Co-Investigator / PI: Ricardo Soto
2021-2025: Fondecyt 1211547
“Understanding Liquid-liquid Phase Separation during the retroviral life cycle”
Principal Investigator
2020-2023: Fondecyt Postdoctorado 3200556
“Indetifying host cell factors that control HIV-1 Latency in different types of latente reservoirs”
Co-Investigator / PI: Chantal Márquez
Anillos de Investigación en Ciencia y/o Tecnología: Regular y Áreas Temáticas
2022-2025: Anillo ATE220016
Anillo inflammattion in HIV/AIDS (InflammAIDS)
Associate Investigator / Director: Ricardo Soto-Rifo (UCHILE)
2022-2025: Anillo ATE220034
Integrated multi-omic immune profiling of human RNA respiratory viruses: current and future pandemics
Principal Investigator / Director: María Inés Barría (USS)
2022-2025: Anillo ATE220007
Integrative approaches to assess the microbiome in the built environment MicroBE in the Covid era: the school-microbe initiative
Associate Investigator / Director: Claudia Saavedra (UNAB)
Proyectos de investigación y desarrollo en salud FONIS
2021-2024: Fonis SA21I0078
“Seguimiento y monitoreo clínico-molecular de pacientes reumatológicos inoculados con vacunas para SARS-CoV-2 en la región de Atacama”
Associate Investigator / PI: María José Gallardo (UDA)
Internacionales
2023-2025: Fomento Vinculación Internacional para Instituciones de Investigación Regionales FOVI230163
Fortalecimiento de la vinculación internacional en el área de enfermedades infecciosas virales en el sur de Chile, ciencia fundamental y aplicaciones traslacionales
Associate Investigator / PI: María Inés Barria (Panamá)
2022-2024: Convocatoria Pública de Fomento a I+D (FID) 2022 – SENACYT FID22-079
Respuesta inmune a largo plazo en pacientes recuperados de COVID19 y vacunados anti-SARS-CoV-2 en Panamá
Associate Investigator / PI: Sandra López (Panamá)
2023-2026: Consejo Nacional de Ciencia y Tecnología CONACYT -Paraguay
Desarrollo de un sistema pseudoviral para el virus chikungunya con aplicación en la busqueda de antivirales y la evaluación de anticuerpos neutralizantes
Associate Investigator / PI: Pablo Sotelo (Paraguay)
SpinOff Viral Tools & Diagnostics
2024-2025: Start-Up Ciencia 2024 SUC240103
FluggY Forte suplemento inmunoprotector contra el virus influenza A de alta patogenicidad H5N1 y sus variantes de impacto en la industria de carnes blancas.
Director: Daniel Henríquez
2024-2025: Crea y Valida 23CVC2-251437
FluggY suplemento inmunoprotector contra Virus de Influenza Aviar de alta patogenicidad H5N1
Director: Daniel Henríquez
2023-2025: Fundación para la Innovación Agraria (FIA) PYT-2023-0575
Desarrollo de suplemento inmunoprotector contra Influenza Aviar de alta patogenicidad H5N1 para aves de industria avicola
Director: Daniel Henríquez
2022-2023: Start-Up Ciencia 2022 SUC220121
ViralNeutra Plex – Plataforma de detección de anticuerpos neutralizantes contra SARS-CoV-2 y sus variantes.
Director: Daniel Henríquez
Past Research Support
2019-2023: Fondecyt 1190156
“m6A switches as drivers of retroviral genomic RNA selection for packaging”
Co-Investigator / PI: Ricardo Soto-Rifo
2019-2020: Proyecto de Internacionalización UCH-1566
“Estudio de resistencia y variamtes del VIH en pacientes con fracaso virológico en Chile”
Co-Investigador / PI: Carolina Beltrán
2018-2021: Fondecyt 1180798
“RNAstasis during HIV-1 replication”
Principal Investigator
2016-2019: Fondecyt 11160176
“HIV gene expression in the RNA epigenetics era”
Co- Investigator
2016-2018: U-Genoma – Universidad de Chile
Red de Investigación y Docencia en Genética y Genómica
Associate Investigator
2017-2019: Fondef 16I10017
“Development of a HTS system for the identification of HIV-1 gene expression inhibitors”
Deputy Director
2014-2017 Fondecyt Initiation in Research Grant 11140502
“Role of ribonucleoprotein (RNP) Granules and anticancer drugs (ACDs) in HIV-1 replication”
Principal Investigator
2013-2016: Conicyt USA2013-0005
“The atlas of the HIV-1 genomic messenger ribonucleoprotein (mRNP) complex”
Co-Principal Investigator