Dra. Rosa Ma. del Angel Núñez de Cáceres

Nuestro grupo esta dedicado al análisis de los mecanismos y componentes celulares que usan los virus de la familia Flaviviridae como Dengue, Zika y el virus del Fiebre amarilla para entrar, replicarse, inhibir la respuesta inmune celular y salir de la célula. Este estudio nos ha permitido encontrar factores que favorecen y otros que evitar la multiplicación viral en las células infectadas.

Con esta información hemos identificado moléculas y componentes que son capaces de bloquear la infección por estos virus y estamos probando su utilidad como antivirales en sistemas de cultivos de células y en modelos animales.

Por otro lado, trabajamos en la identificación de mecanismos de comunicación celular como son los exosomas en las células de mosquito y su participación en la patogenia de la infección por Dengue.

2012

  • de la Cruz Hernandez, S.I., González Mateos, S., Flores Aguilar, H., López Martínez, I.,Alpuche Aranda, C., Ludert, J.E., del Angel, R.M. 2012. Evaluation of a novel comercial rapid test for dengue diagnosis base don specific IgA detection. Diagn Microbiol. Infect Dis. 72:150-155.

  • Puerta-Guardo, H. De la Cruz Hernández, S.I., Rosales, V.H., Ludert, J.E. and del Angel, R.M. 2012. The 1 alfa, 25-Dyhidroxy-Vitamin D3 reduces dengue virus infection in human myelomonocyte (U937) and hepatic (Huh-7) cell lines and cytokine production in the infected monocytes. Antiviral Res 94:57-61

2013

  • Juárez-Martínez, A.B., Salas-Benito, M., García-Espitia. M. De Nova-Ocampo, M. del Ángel, R.M. and Salas-Benito, J.S. 2013. Detection and sequencing of defective viral genomes in C6/36 cells persistently infected with dengue virus 2. Arch Virol. 158:583-599.

  • De la Cruz-Hernandez, S.I., Flores-Aguilar, H., Gonzalez-Mateos, S., Lopez-Martinez, I., Alpuche-Aranda, C., Ludert, J.E., del Angel, R.M. 2013. Determination of viral load and concentration of circulating NS1 protein in an open mexican population infected with dengue virus. Am. J. Trop. Med Hyg. 88:446-454.

  • Vega-Almeida TO, Salas-Benito M, De Nova-Ocampo MA, Del Angel RM, Salas-Benito JS.- 2013. Surface proteins of C6/36 cells involved in dengue virus 4 binding and entry.- Arch Virol. 158:1189-1207

  • Soto-Acosta R, Mosso C, Cervantes-Salazar M, Puerta-Guardo H, Medina F, Favari L, Ludert JE, Del Angel RM. 2013. The increase in cholesterol levels at early stages after dengue virus infection correlates with an augment in LDL particle uptake and HMG-CoA reductase activity. Virology.442:132-147.

  • Puerta-Guardo H, Sandino AR, González-Mariscal L, Rosales VH, Ayala-Dávila J, Chávez- Mungía B, Martínez-Fong D, Medina F, Ludert JE, Del Angel RM. 2013. The cytokine response of U937-derived macrophages infected through antibody dependent enhancent of dengue virus disrupts cell apical junctional complexes and increase vascular permeability. J Virol. 87:7486-7501

  • De La Cruz Hernández SI, Ortiz-Navarrete V, Ludert JE, Del Angel RM. 2013. Dengue specific IgM seropositivity correlates with severe clinical outcome J Clin Virol. 58:751.

  • De La Cruz Hernández SI, Flores-Aguilar H, González-Mateos S, López-Martínez I, Ortiz-Navarrete V, Ludert JE, Del Angel RM. 2013. Viral load in patients infected with dengue is modulated by the presence of anti-dengue IgM antibodies.- J Clin Virol. 58:258-61.

  • Del Angel RM, Reyes-del Valle J.- 2013. Dengue vaccines: strongly sought but not a reality just yet.- PLoS Pathog.;9(10):e1003551. doi: 10.1371/journal.ppat.1003551. PMID:24098108.

2014

  • Reyes-del Valle, J., Salas-Benito J., Soto-Acosta, R., and del Angel R.M. 2014. Dengue virus celular receptors and tropism. Current Trop. Med. Reports. 1:36-43.

  • Alcaraz-Estrada SL, Del Angel R, Padmanabhan R. 2014. Construction of self-replicating subgenomic dengue virus 4 (DENV4) replicon. Methods Mol Biol. 2014;1138:131-50.

  • De La Cruz Hernández SI, Puerta-Guardo H, Flores-Aguilar H, González-Mateos S, López- Martinez I, Ortiz-Navarrete V, Ludert JE, Del Angel RM. 2014. A strong interferon response correlates with a milder dengue clinical condition. J Clin Virol. 60:196-199.

  • Salazar MI, Del Angel RM, Lanz-Mendoza H, Ludert JE, Pando-Robles V. 2014. The role of cell proteins in dengue virus infection. J Proteomics. 111:6-15.

  • Soto-Acosta R, Bautista-Carbajal P, Syed GH, Siddiqui A, Del Angel RM. 2014. Nordihydroguaiaretic acid (NDGA) inhibits replication and viral morphogenesis of dengue virus. Antiviral Res. 109:132-140.

  • Cabrera-Romo, S., Recio-Totoro, B., Alcala , Ana C., Lanz, H., del Angel, R.M. Sanchez-Cordero, V., Rodriguez-Moreno, A. and Ludert, J.A. 2014. Experimental Inoculation of Artibeus jamaicensis Bats with Dengue Virus Serotypes 1 or 4 Showed No Evidence of Sustained Replication. Am J. Trop.Med & Hyg. 91:1227-1234.

  • Betancourt-Cravioto M, Kuri-Morales P, González-Roldán JF, Tapia-Conyer R; Mexican Dengue Expert Group. 2014. Introducing a dengue vaccine to Mexico: development of a system for evidence-based public policy recommendations. PLoS Negl Trop Dis. 31:e3009. doi: 10.1371/journal.pntd.0003009.

2015

  • De La Cruz Hernández, SI, Reyes-del Valle, J, Villegas-del Angel, E., Ludert JE and Del Angel RM. 2015. Dengue Laboratory Diagnosis: still some room for improvement . Future Virol. 10: 845-857

  • Cervantes-Salazar, M, Angel-Ambrocio, AH, Soto-Acosta, R, Bautista-Carbajal, P, Hurtado-Monzón, AM, Alcaraz-Estrada, SL, Ludert, JE, Del Angel, RM. 2015. Dengue virus NS1 protein interacts with the ribosomal protein RPL18: This interaction is required for viral translation and replication in Huh-7 cells. Virology 484: 113–126.

2016

  • Alcalá AC, Medina F, González-Robles A, Salazar-Villatoro L, Fragoso-Soriano RJ, Vásquez C, Cervantes-Salazar M, Del Angel RM, Ludert JE. 2016. The dengue virus non-structural protein 1 (NS1) is secreted efficiently from infected mosquito cells. Virology. 488:278-287.

  • de la Cruz Hernández SI, Puerta-Guardo HN, Flores Aguilar H, González Mateos S, López Martinez I, Ortiz-Navarrete V, Ludert JE, Del Angel RM. 2016. Primary dengue virus infections induce differential cytokine production in Mexican patients. Mem Inst Oswaldo Cruz 111: 161-167.

  • Cabrera-Romo S, Max Ramirez C, Recio-Tótoro B, Tolentino-Chi J, Lanz H, Del Ángel RM, Sánchez-Cordero V, Rodríguez-Moreno Á, Ludert JE. 2016. No Evidence of Dengue Virus Infections in Several Species of Bats Captured in Central and Southern Mexico. Zoonoses Public Health. 63:579-583.

2017

  • Bautista-Carbajal P, Soto-Acosta R, Angel-Ambrocio AH, Cervantes-Salazar M, Loranca-Vega CI, Herrera-Martínez M, Del Angel RM. 2017. The calmodulin antagonist W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride) inhibits DENV infection in Huh-7 cells. Virology 501:188-198.

  • Avila-Bonilla RG, Yocupicio-Monroy M, Marchat LA, De Nova-Ocampo MA, Del Ángel RM, Salas-Benito JS. 2017. Analysis of the miRNA profile in C6/36 cells persistently infected with dengue virus type 2. Virus Res. 232:139-151

  • Soto-Acosta, R., Bautista-Carbajal, P, Cervantes-Salazar, M, Angel Ambrocio, AH and del Angel R.M 2017. DENV Up-Regulates the HMG-CoA Reductase Activity through the Impairment of AMPK Phosphorylation: A Potential Antiviral Target. Plos Pathogen. 10.1371/journal.ppat.1006257.

  • Alcalá AC, Hernández-Bravo R, Medina F, Coll DS, Zambrano JL, Del Angel RM, Ludert JE. 2017. The dengue virus non-structural protein 1 (NS1) is secreted from infected mosquito cells via a non-classical caveolin-1-dependent pathway. J Gen Virol. 98:2088-2099.

  • Trujillo-Ocampo A, Cázares-Raga FE, Del Angel RM, Medina-Ramírez F, Santos-Argumedo L, Rodríguez MH, Hernández-Hernández FC. 2017. Participation of 14-3-3e and 14-3-3? proteins in the phagocytosis, component of cellular immune response, in Aedes mosquito cell lines. Parasit Vectors 10:362.

2018

  • Dionicio CL, Peña F, Constantino-Jonapa LA, Vazquez C, Yocupicio-Monroy M, Rosales R, Zambrano JL, Ruiz MC, Del Angel RM, Ludert JE. 2018. Dengue virus induced changes in Ca2+ homeostasis in human hepatic cells that favor the viral replicative cycle. Virus Res. 245:17-28.

  • Reyes-Ruiz JM, Osuna-Ramos JF, Cervantes-Salazar M, Lagunes Guillen AE, Chávez-Munguía B, Salas-Benito JS, Del Ángel RM. 2018. Strand-like structures and the nonstructural proteins 5, 3 and 1 are present in the nucleus of mosquito cells infected with dengue virus. Virology. 515:74-80.

  • Elizondo-Quiroga D, Medina-Sánchez A, Sánchez-González JM, Eckert KA, Villalobos-Sánchez E, Navarro-Zúñiga AR, Sánchez-Tejeda G, Correa-Morales F, González-Acosta C, Arias CF, López S, Del Ángel RM, Pando-Robles V, Elizondo-Quiroga AE. 2018. Zika Virus in Salivary Glands of Five Different Species of Wild-Caught Mosquitoes from Mexico. Scientific Rep. 8:809. doi: 10.1038/s41598-017-18682-3.

  • Osuna-Ramos JF, Rendón-Aguilar H, Reyes-Ruiz JM, Del Ángel RM, Romero-Utrilla A, Ríos-Burgueño ER, Velarde-Rodriguez I, Velarde-Félix JS. 2018. The correlation of TNF alpha levels with the lipid profile of dengue patients. J. Med Virol. 90:1160-1163.

  • Apodaca-Medina AI, Torres-Avendaño JI, Rendón-Maldonado JG, Torres-Montoya EH, Flores-López BA, Del Angel RM, Velarde-Félix JS, Salomón-Soto VM, Castillo-Ureta H. 2018. First Evidence of Vertical Infection of Dengue Virus 2 in Aedes aegypti Mosquitoes from Sinaloa, Mexico. Vector Borne Zoonotic Dis. 18:231-233.

  • Taboada B, Isa P, Gutiérrez-Escolano AL, Del Ángel RM, Ludert JE, Vázquez N, Tapia-Palacios MA, Chávez P, Garrido E, Espinosa AC, Eguiarte LE, López S, Souza V, Arias CF. 2018. The viral structure of the Cuatro Ciénegas Basin, a unique oasis in Northern Mexico, reveals a highly diverse population at a small geographic scale. Appl Environ Microbiol. AEM.00465-18. doi: 10.1128/AEM.00465-18.

  • Ramirez L, Betanzos A, Raya A, González-Mariscal L, Del Angel RM. 2018. Dengue virus enters and exits epithelial cells through both apical and basolateral surfaces and perturbs the apical junctional complex. Virus Res. 258:39-49. doi: 10.1016/j.virusres.2018.09.016.

  • Osuna-Ramos JF, Reyes-Ruiz JM, Bautista-Carbajal P, Cervantes-Salazar M, Farfan-Morales CN, De Jesús-González LA, Hurtado-Monzón AM, Del Ángel RM. 2018. Ezetimibe inhibits dengue virus infection in Huh-7 cells by blocking the cholesterol transporter Niemann-Pick C1-like 1 receptor. Antiviral Res. 160:151-164.

  • Osuna-Ramos JF, Reyes-Ruiz JM, Del Ángel RM. 2018. The Role of Host Cholesterol During Flavivirus Infection. Front Cell Infect Microbiol. 8:388. doi: 10.3389/fcimb.2018.00388.

  • Tammineni ER, Carrillo ED, Soto-Acosta R, Angel-Ambrocio AH, García MC, Bautista-Carbajal P, Del Angel RM, Sánchez JA. 2018. The ß4 subunit of Cav1.2 channels is required for an optimal interferon response in cardiac muscle cells. Sci Signal. 11(560). pii: eaaj1676. doi: 10.1126/scisignal.aaj1676.

2019

  • Reyes-Ruiz JM, Osuna-Ramos JF, Bautista-Carbajal P, Jaworski E, Soto-Acosta R, Cervantes-Salazar M, Angel-Ambrocio AH, Castillo-Munguía JP, Chávez-Munguía B, De Nova-Ocampo M, Routh A, Del Ángel RM, Salas-Benito JS. 2019. Mosquito cells persistently infected with dengue virus produce viral particles with host-dependent replication. Virology. 531:1-18. doi: 10.1016/j.virol.2019.02.018.

  • Reyes-Ruiz JM, Osuna-Ramos JF, De Jesús-González LA, Hurtado-Monzón AM, Farfan-Morales CN, Cervantes-Salazar M, Bolaños J, Cigarroa-Mayorga OE, Martín-Martínez ES, Medina F, Fragoso-Soriano RJ, Chávez-Munguía B, Salas-Benito JS, Del Angel RM. 2019. Isolation and characterization of exosomes released from mosquito cells infected with dengue virus. Virus Res. 266:1-14. doi: 10.1016/j.virusres.2019.03.015.

  • Pérez-Olais JH, Ruiz-Jiménez F, Calderón-Garcia EJ, De Jesús-González LA, Hernández-Rivas R, Del Angel RM. 2019. The Activity of Aurora Kinase B Is Required for Dengue Virus Release. Virus Res. 274:197777. doi: 10.1016/j.virusres.2019.197777.

2020

  • Hurtado-Monzón AM, Cordero-Rivera CD, Farfan-Morales CN, Osuna-Ramos JF, De Jesús-González LA, Reyes-Ruiz JM, Del Ángel RM. 2020. The Role of Anti-Flavivirus Humoral Immune Response in Protection and Pathogenesis. Rev. Med Virol. e2100. doi: 10.1002/rmv.2100.

  • De Jesús-González LA, Cervantes-Salazar M, Reyes-Ruiz JM, Osuna-Ramos JF, Farfán-Morales CN, Palacios-Rápalo SN, Pérez-Olais JH, Cordero-Rivera CD, Hurtado-Monzón AM, Ruíz-Jiménez F, Gutiérrez-Escolano AL, Del Ángel RM. 2020. The Nuclear Pore Complex: A Target for NS3 Protease of Dengue and Zika Viruses. Viruses 26;12(6):E583. doi: 10.3390/v12060583.

  • Avila-Bonilla RG, Yocupicio-Monroy M, Marchat LA, Pérez-Ishiwara DG, Cerecedo-Mercado DA, Del Ángel RM, Salas-Benito JS. 2020. miR-927 Has Pro-Viral Effects During Acute and Persistent Infection With Dengue Virus Type 2 in C6/36 Mosquito Cells. J Gen Virol. doi: 10.1099/jgv.0.001441.

  • Guzmán-Tellez P., Martíonez-Valencia D, Dsilva-Oliovares A, del Angel R.M., Serrano-Lunma, J, and Shibayama M. 2020. Naegleria fowleri and Naegleria gruberi 20S proteasome: identification and characterization. European Journal of Cell Biology DOI: 0.1016/j.ejcb.2020.151085

  • Reyes-Ruiz JM, Osuna-Ramos JF, De Jesús-González LA, Palacios-Rápalo SN, Cordero-Rivera CD, Farfan-Morales CN, Hurtado-Monzón AM, Gallardo-Flores CE, Alcaraz-Estrada SL, Salas-Benito JS, Del Ángel RM. 2020. The Regulation of Flavivirus Infection by Hijacking Exosome-Mediated Cell-Cell Communication: New Insights on Virus-Host Interactions. Viruses 12(7):E765. doi: 10.3390/v12070765

Doctorado 25

Mestría 42