Rosa Del Angel

Rosa Del Angel
Center for Research and Advanced Studies of the National Polytechnic Institute | Cinvestav · Departamento de Infectómica y Patogénesis Molecular

PhD

About

127
Publications
23,221
Reads
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3,138
Citations
Introduction
Our group is actually involved in the analysis of cellular mechanisms and components used by Flaviviridae family members such as Dengue, Zika and Yellow Fever virus to enter, replicate, inhibit the cellular immune response and exit the host cell. This study has allowed us to find cellular factors that favor and others that avoid viral multiplication in infected cells. With this information we have identified molecules and components that are capable to block viral infection
Additional affiliations
May 2015 - May 2019
Center for Research and Advanced Studies of the National Polytechnic Institute
Position
  • Head of Department
January 1990 - December 2012
Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional
Position
  • Dengue virus replication
Description
  • Investigation in Virology area, mainly focus on dengue virus entry, replication and pathogenesis
November 1987 - December 1999
Columbia University
Position
  • Attenuation in poliovirus
Description
  • During my PhD thesis I spent several months in Dr. Racaniello's lab.
Education
April 1988 - May 1990
August 1984 - March 1988
August 1979 - December 1983
Universidad La Salle México
Field of study
  • Química Farmacobióloga

Publications

Publications (127)
Article
Full-text available
The emergence and rapid increase of the B.1.1.7 (Alpha) lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout the world were due to its increased transmissibility. However, it did not displace cocirculating lineages in most of Mexico, particularly B.1.1.519, which dominated the country from February to May 2021.
Article
Full-text available
COVID-19 and dengue disease are challenging to tell apart because they have similarities in clinical and laboratory features during the acute phase of infection, leading to misdiagnosis and delayed treatment. The present study evaluated peripheral blood cell count accuracy to distinguish COVID-19 non-critical patients from non-severe dengue cases b...
Article
Full-text available
Since its appearance, the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), the causal agent of Coronavirus Disease 2019 (COVID-19), represents a global problem for human health that involves the host lipid homeostasis. Regarding, lipid rafts are functional membrane microdomains with highly and tightly packed lipid molecules. These region...
Article
Full-text available
Although Flaviviruses such as dengue (DENV) and zika (ZIKV) virus are important human pathogens, an effective vaccine or antiviral treatment against them is not available. Hence, the search for new strategies to control flavivirus infections is essential. Several studies have shown that the host lipid metabolism could be an antiviral target because...
Article
Full-text available
The risk of coronavirus disease 2019 (COVID-19) and dengue coinfection is increased in tropical countries; however, the extrapulmonary clinical manifestations have not been fully characterized. We report a 42-year-old woman whose clinical manifestations began with fever, diarrhea, headache, chest pain, myalgia, odynophagia, and arthralgia. Despite...
Article
The flavivirus are emerging and re-emerging arthropod-borne pathogens responsible for significant mortality and morbidity worldwide. The genus comprises more than 70 viruses, and despite genomic and structural similarities, infections by different flaviviruses result in different clinical presentations. In the absence of a safe and effective vaccin...
Article
Full-text available
The Dengue (DENV) and zika (ZIKV) virus infections are currently a public health concern. At present, there is no treatment or a safe and effective vaccine for these viruses. Hence, the development of new strategies as host-directed therapy is required. In this sense, Metformin (MET), an FDA-approved drug used for the treatment of type 2 diabetes,...
Article
Full-text available
Various viruses alter nuclear pore complex (NPC) integrity to access the nuclear content favoring their replication. Alteration of the nuclear pore complex has been observed not only in viruses that replicate in the nucleus but also in viruses with a cytoplasmic replicative cycle. In this last case, the alteration of the NPC can reduce the transpor...
Article
Full-text available
Although dengue virus (DENV) replication occurs in the cytoplasm, the nucleus plays an essential role during infection. Both the capsid protein (C) and non-structural protein 5 (NS5) are translocated into the infected cell nucleus to favor viral replication. Previously, our group reported the nuclear localization of the NS3 protein during DENV infe...
Article
Dengue virus (DENV) infection elevates intracellular Ca²⁺ concentration ([Ca²⁺]i), but it is unknown whether Ca²⁺ and calmodulin (CaM) are involved in DENV infection. We conducted immunofluorescence and western blot experiments and measured [Ca²⁺]i examining the effects of DENV infection and drugs that alter Ca²⁺/CaM functions on CaM translocation,...
Preprint
Full-text available
Background: COVID-19 has been recognized as an emerging and rapidly evolving health condition. For this reason, efforts to determine changes in laboratory parameters of COVID-19 patients as biomarkers are urgent. Lipids are essential components of the human body, and their modulation has been observed implicated in some viral infections. Methods: T...
Preprint
Full-text available
The recent epidemic of COVID-19 caused by SARS-CoV-2 was declared by the World Health Organization as a public health emergency of international concern. The absence of an approved vaccine or a specific antiviral drug has made bioinformatic tools crucial for the identification of potential therapeutic targets and drugs for its control. As in other...
Preprint
Full-text available
The recent epidemic of COVID-19 caused by SARS-CoV-2 was declared by the World Health Organization as a public health emergency of international concern. The absence of an approved vaccine or a specific antiviral drug has made bioinformatic tools crucial for the identification of potential therapeutic targets and drugs for its control. As in other...
Article
Full-text available
The arthropod-borne flaviviruses are important human pathogens, and a deeper understanding of the virus-host cell interaction is required to identify cellular targets that can be used as therapeutic candidates. It is well reported that the flaviviruses hijack several cellular functions, such as exosome-mediated cell communication during infection,...
Article
Dengue virus (DENV) is an important flavivirus that is transmitted to humans by Aedes mosquitoes, where it can establish a persistent infection underlying vertical and horizontal transmission. However, the exact mechanism of persistent DENV infection is not well understood. Recently miR-927 was found to be upregulated in C6/36-HT cells at 57 weeks...
Article
Full-text available
During flavivirus infection, some viral proteins move to the nucleus and cellular components are relocated from the nucleus to the cytoplasm. Thus, the integrity of the main regulator of the nuclear-cytoplasmic transport, the nuclear pore complex (NPC), was evaluated during infection with dengue virus (DENV) and Zika virus (ZIKV). We found that whi...
Article
The Naegleria are ubiquitous free-living amoebae and are characterized by the presence of three phases in their biological cycle: trophozoite, cyst and flagellate. Of this genus, only Naegleria fowleri has been reported as pathogenic to humans. The proteasome is a multi-catalytic complex and is considered to be the most important structure responsi...
Article
Flavivirus infections are a public health threat in the world that requires the development of safe and effective vaccines. Therefore, the understanding of the anti-flavivirus humoral immune response is fundamental to future studies on flavivirus pathogenesis and the design of anti flavivirus therapeutics. This review aims to provide an overview of...
Article
Flaviviruses, such as Dengue (DENV), Zika, Yellow Fever, Japanese Encephalitis and West Nile are important pathogens with high morbidity and mortality. The last estimation indicates that ∼390 millions of people are infected by DENV per year. The DENV replicative cycle occurs mainly in the cytoplasm of the infected cells and different cytoplasmic, n...
Article
Dengue viruses (DENV) are important arboviruses that can establish a persistent infection in its mosquito vector Aedes. Mosquitoes have a short lifetime in nature which makes trying to study the processes that take place during persistent viral infections in vivo. Therefore, C6/36 cells have been used to study this type of infection. C6/36 cells pe...
Chapter
The Cuatro Ciénegas Basin (CCB) is a biologically exceptional place. In general, CCB aquatic systems are extremely oligotrophic, but paradoxically they are extraordinarily biodiverse, and viruses are not an exception. Previous studies had shown that two stable ecosystems within CCB had very different virus; one of them, Pozas Azules, presented dive...
Article
Full-text available
The auxiliary β 4 subunit of the cardiac Ca v 1.2 channel plays a poorly understood role in gene transcription. Here, we characterized the regulatory effects of the β 4 subunit in H9c2 rat cardiac cells on the abundances of Ifnb mRNA [which encodes interferon-β (IFN-β)] and of the IFN-β–related genes Ddx58 , Ifitm3 , Irf7 , Stat2 , Ifih1 , and Mx1...
Article
Full-text available
In recent years the emergence and resurgence of arboviruses have generated a global health alert. Among arboviruses, Dengue (DENV), Zika (ZIKV), Yellow Fever (YFV) and West Nile (WNV) virus, belong to the genus Flavivirus, cause high viremia and occasionally fatal clinical disease in humans. Given the genetic austerity of the virus, they depend on...
Article
Despite the importance of Dengue virus (DENV) infection in human health, there is not a fully effective vaccine or antiviral treatment against the infection. Since lipids such as cholesterol are required during DENV infection, its uptake and synthesis are increased in infected cells. Ezetimibe is an FDA-approved drug that reduces cholesterol uptake...
Article
Dengue is the most relevant mosquito-borne viral disease in the world. It has been estimated that 390 million infections of dengue occur each year. Dengue virus (DENV) infection can be asymptomatic or can produce a self-limited febrile illness called dengue fever (DF) or a severe form of the infection called severe dengue. In some viruses, the entr...
Preprint
Full-text available
Despite the importance of Dengue virus (DENV) infection in human health, there is not a fully effective vaccine or antiviral treatment against the infection. Since lipids such as cholesterol are required during DENV infection, its uptake and synthesis are increased in infected cells. Ezetimibe is an FDA-approved drug that reduces cholesterol uptake...
Preprint
Full-text available
Viruses hijack cellular proteins and components to be replicated in the host cell and to evade the immune response. Although flaviviruses have a cytoplasmic replicative cycle, some viral proteins such as the capsid (C) and the RNA dependent RNA polymerase, NS5, can reach the nucleus of the infected cells. Considering the important roles of NS5 in v...
Article
Full-text available
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Article
Full-text available
The Cuatro Ciénegas Basin (CCB) is located in the Chihuahuan desert in the Mexican state of Coahuila; it has been characterized as a site with high biological diversity despite its extreme oligotrophic conditions. It has the greatest number of endemic species in North America, containing abundant living microbialites (including stromatolites and mi...
Article
Fourteen pools of Aedes aegypti larvae collected within the urban area of Culiacán, Sinaloa, were analyzed by RT-PCR. The results demonstrate, for the first time, the vertical infection of serotype-2 dengue virus (DENV-2) in Sinaloa, Mexico, suggesting that Ae. aegypti acts as a natural reservoir of DENV-2 in this region.
Article
Immunological factors, such as cytokines, have been proposed as a cause of changes in the lipid profile of dengue patients. We studied whether serum lipid levels and serum TNF-α levels are associated in a group of dengue patients from an endemic region in the northwest of Mexico. We found statistically important differences in the serum lipid profi...
Article
Dengue virus (DENV) is an arbovirus, which replicates in the endoplasmic reticulum. Although replicative cycle takes place in the cytoplasm, some viral proteins such as NS5 and C are translocated to the nucleus during infection in mosquitoes and mammalian cells. To localized viral proteins in DENV-infected C6/36 cells, an immunofluorescence (IF) an...
Article
Full-text available
Zika virus (ZIKV) is a mosquito-borne pathogen, and Aedes aegypti has been identified as the main vector of the disease. Other mosquito species in the Aedes and Culex genera have been suggested to have the potential for being competent vectors based on experimental exposition of mosquitoes to an infectious blood meal containing ZIKV. Here, we repor...
Conference Paper
Full-text available
Flaviviruses, such as Dengue (DENV), Zika, Yellow Fever, Japanese Encephalitis and West Nile are the causative pathogens of infections with high morbidity rates. The last estimation indicated that ~370 millions of people are infected by DENV per year and almost 90 million develop different clinic forms of the infection. The interaction between vira...
Conference Paper
Full-text available
Dengue is a systemic viral infection caused by the dengue virus (DENV), a member of the Flaviviridae family of the genus Flavivirus. The serocomplex of dengue virus (DENV 1 to DENV 4) is transmitted to humans by Aedes mosquitoes, causing more than 96 million infections per year in 100 countries around the world. Currently, there is not fully effect...
Article
Full-text available
Background Better knowledge of the innate immune system of insects will improve our understanding of mosquitoes as potential vectors of diverse pathogens. The ubiquitously expressed 14-3-3 protein family is evolutionarily conserved from yeast to mammals, and at least two isoforms of 14-3-3, the ε and ζ, have been identified in insects. These protei...
Article
Full-text available
Dengue virus NS1 is a glycoprotein of 46-50 kDa that is conserved among flaviviruses, associates as a dimer to cell membranes and is secreted as a hexamer to the extracellular milieu. Recent evidence showed that NS1 is secreted efficiently from infected mosquito cells. To explore the secretory route of NS1 in mosquito cells, infected cells were tre...
Chapter
Dengue is the mosquito-borne viral disease that is most important to humans. In the Americas, a region highly endemic for dengue, all four serotypes circulate. Accordingly, many researchers in the region have devoted their efforts to the study and control of this disease. Research carried out in the region has significantly helped in the understand...
Article
Full-text available
Dengue is the most common mosquito-borne viral disease in humans. Changes of lipid-related metabolites in endoplasmic reticulum of dengue virus (DENV) infected cells have been associated with replicative complexes formation. Previously, we reported that DENV infection inhibits HMGCR phosphorylation generating a cholesterol-enriched cellular environ...
Data
Intracellular distribution of HMGCR and NS4A viral protein during DENV infection using electron microscopy. The closeness between both proteins was corroborated by electron microscopy in DENV4 infected Huh7 cells using a goat anti-HMGCR antibody coupled to a 10 nm gold particle (Small dots, HMGCR), and a rabbit anti-NS4A antibody coupled to a 30 nm...
Data
HMGCR and NS3 protein distribution and colocalization. The distribution of HMGCR and components of viral replication complexes (NS3 and E viral proteins) was evaluated by confocal microscopy in Huh7 cells infected with DENV2 (MOI 3) and treated with DMSO 0.5% (vehicle), 10 mM Metformin or 50 μM lovastatin (HMGCR inhibitor) for 24h. The integrity of...
Data
Distribution of NS4A-eGFP in Huh7 cells in response to treatment with AMPK activators and lovastatin. Huh7 cells were transfected with a plasmid encoding NS4A-eGFP [46] and 24 hours after transfection, cells were treated with DMSO 0.5% (VEH), 10 mM metformin (MET) 100 μM TMPA, 120 μM A769662 and 50 μM lovastatin for 24 h. Distribution of NS4A-eGFP...
Data
Antiviral effect of AMPK activators and lovastatin. Huh7 cells were infected with DENV2 at a MOI 3 and treated for 24 h with metformin (MET 1 mM, 5 mM and 10 mM), TMPA (25, 50, 100 μM), A-769662 (30, 60, 120 μM) and lovastatin (LOV 12.5, 25, 50 mM). Percentage of infected cells was analyzed by flow cytometry (A) and histograms (B) depicting the mea...
Data
Double strand RNA (dsRNA) analysis in infected cells treated with metformin. Huh7 cells were infected with DENV2 and treated with metformin10 mM or vehicle, and 24 hpi cells were fixed and stained for double strand RNA (antibody) and analyzed by flow cytometry. Graph represents the dsRNA mean fluorescence intensity from 3 experiments, Histograms ar...
Data
Huh7 cell viability after metformin, TMPA, A- 769662, compound C, lovastain and okadaic acid treatment. Cell viability was evaluated in Huh7 cells treated with drugs and concentrations indicated in the graph for 24 h using the cell proliferation assay CellTiter 96 AQueous (Promega). (TIF)
Data
AMPK inhibition induced by compound C encourages DENV infection. In A, The infection increase was evaluated by FACS using a mouse anti-E monoclonal antibody-4G2 to detect the E viral protein in Huh7 cells infected with Mock or DENV 2/4 (MOI 0.3), and treated with 10μM compound C (CC) or DMSO 0.5% (vehicle) for 24h. Upper histograms display the fluo...
Data
Distribution of eGFP in Huh7 cells in response to treatment with AMPK activators and lovastatin. Huh7 cells were transfected with a plasmid codifying just eGFP [46] and 24 hours after, transfected cells were treated with DMSO 0.5% (VEH), 10 mM metformin (MET) 100 μM TMPA, 120 μM A-769662 and 50 μM lovastatin for 24 h. Distribution of eGFP (green) w...
Article
Dengue virus (DENV) is the most important arbovirus in the world; DENV is transmitted by the Aedes genus of mosquitoes and can establish a life-long persistent infection in mosquitoes. However, the exact mechanism by which persistent infection is established remains unknown. In this study the differential expression of miRNAs was analysed by deep s...
Article
Dengue virus (DENV) replicative cycle occurs in the endoplasmic reticulum where calcium ions play an important role in cell signaling. Calmodulin (CaM) is the primary sensor of intracellular Ca²⁺ levels in eukaryotic cells. In this paper, the effect of the calmodulin antagonist W-7 in DENV infection in Huh-7 cells was evaluated. W7 inhibited viral...
Article
Bats are reservoirs for viruses with zoonotic potential in the Americas, and scattered evidence exists suggesting that bats may act as reservoirs for dengue virus (DENV). To explore further the role of bats as part of DENV sylvatic cycles, 240 bats of 18 species were captured in 2 states of Mexico with contrasting ecological characteristics but con...
Conference Paper
Full-text available
Dengue is the most important mosquito-borne viral disease in the world. The infection with any of the 4 dengue virus serotypes (DENV) produces a wide range of clinical conditions ranging from the mild form called dengue fever to the more severe form known as dengue hemorrhagic fever that may progress into dengue shock syndrome. During DENV infectio...
Article
Full-text available
Severe dengue pathogenesis is not fully understood, but high levels of proinflammatory cytokines have been associated with dengue disease severity. In this study, the cytokine levels in 171 sera from Mexican patients with primary dengue fever (DF) and dengue haemorrhagic fever (DHF) from dengue virus (DENV) 1 (n = 116) or 2 (n = 55) were compared....
Article
L-type voltage gated Ca2+ channels play a critical role in E-C coupling in cardiac muscle. α1C is associated with β auxiliary subunits (β1-β4), which regulate cardiac Ca2+ channel gating properties. Here we report a novel role of β4 subunit in heart. We observed that β4 subunit is located in the nuclei of H9c2 cells and that overexpression of β4 su...
Article
Dengue virus NS1 is a glycoprotein of 46-50kDa which associates as a dimer to internal and cytoplasmic membranes and is also secreted, as a hexamer, to the extracellular milieu. However, the notion exist that NS1 is secreted only from infected vertebrate and not mosquito cells. In this work, evidence is presented showing that NS1 is secreted effici...
Article
Dengue is the most important and widely distributed arthropod-borne viral disease affecting humans. The number of dengue virus infections has steadily grown and more than 100 countries survey dengue incidence every year. Due to the lack of an approved antiviral treatment or licensed preventative vaccine, accurate and opportune diagnosis is commende...
Article
Given dengue virus (DENV) genome austerity, it uses cellular molecules and structures for virion entry, translation and replication of the genome. NS1 is a multifunctional protein key to viral replication and pathogenesis. Identification of cellular proteins that interact with NS1 may help in further understanding the functions of NS1. In this pape...