Browsing by Author "Pino, Karla"
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- ItemA cis-Acting Element Present within the gag Open Reading Frame Negatively Impacts on the Activity of the HIV-1 IRES(2013) Valiente Echeverria, Fernando; Vallejos, Maricarmen; Monette, Anne; Pino, Karla; Letelier, Alejandro; Huidobro Toro, J. Pablo; Mouland, Andrew J.; López Lastra, Marcelo Andrés
- ItemAndes Virus Antigens Are Shed in Urine of Patients with Acute Hantavirus Cardiopulmonary Syndrome(AMER SOC MICROBIOLOGY, 2009) Godoy, Paula; Marsac, Delphine; Stefas, Elias; Ferrer, Pablo; Tischler, Nicole D.; Pino, Karla; Ramdohr, Pablo; Vial, Pablo; Valenzuela, Pablo D. T.; Ferres, Marcela; Veas, Francisco; Lopez Lastra, MarceloHantavirus cardiopulmonary syndrome (HCPS) is a highly pathogenic emerging disease (40% case fatality rate) caused by New World hantaviruses. Hantavirus infections are transmitted to humans mainly by inhalation of virus-contaminated aerosol particles of rodent excreta and secretions. At present, there are no antiviral drugs or immunotherapeutic agents available for the treatment of hantaviral infection, and the survival rates for infected patients hinge largely on early virus recognition and hospital admission and aggressive pulmonary and hemodynamic support. In this study, we show that Andes virus (ANDV) interacts with human apolipoprotein H (ApoH) and that ApoH-coated magnetic beads or ApoH-coated enzyme-linked immunosorbent assay plates can be used to capture and concentrate the virus from complex biological mixtures, such as serum and urine, allowing it to be detected by both immunological and molecular approaches. In addition, we report that ANDV-antigens and infectious virus are shed in urine of HCPS patients.
- ItemAssociation of single-nucleotide polymorphisms in IL28B, but not TNF-alpha, with severity of disease caused by andes virus(2015) Angulo, Jenniffer; Pino, Karla; Echeverria-Chagas, Natalia; Marco, Claudia; Martinez-Valdebenito, Constanza; Galeno, Héctor; Villagra, Eliecer; Vera, Lilian; Lagos, Natalia; Miquel P., Juan Francisco
- ItemDetection of high biliary and fecal viral loads in patients with chronic hepatitis C virus infection(2017) Monrroy Bravo, Hugo Alfonso; Angulo, J.; Pino, Karla; Labbé, P.; Miquel P., Juan Francisco; López Lastra, Marcelo Andrés; Soza, Alejandro
- ItemEffect of ezetimibe in HCV viral load after liver transplantation(2016) Monrroy Bravo, Hugo Alfonso; Angulo, J.; Pino, Karla; Labbé, P.; López Lastra, Marcelo Andrés; Soza, Alejandro
- ItemFunctional and Structural Analysis of the Internal Ribosome Entry Site Present in the mRNA of Natural Variants of the HIV-1(PUBLIC LIBRARY SCIENCE, 2012) Vallejos, Maricarmen; Carvajal, Felipe; Pino, Karla; Navarrete, Camilo; Ferres, Marcela; Pablo Huidobro Toro, Juan; Sargueil, Bruno; Lopez Lastra, MarceloThe 5'untranslated regions (UTR) of the full length mRNA of the HIV-1 proviral clones pNL4.3 and pLAI, harbor an internal ribosomal entry site (IRES). In this study we extend this finding by demonstrating that the mRNA 5'UTRs of natural variants of HIV-1 also exhibit IRES-activity. Cap-independent translational activity was demonstrated using bicistronic mRNAs in HeLa cells and in Xenopus laevis oocytes. The possibility that expression of the downstream cistron in these constructs was due to alternative splicing or to cryptic promoter activity was ruled out. The HIV-1 variants exhibited significant 5'UTR nucleotide diversity with respect to the control sequence recovered from pNL4.3. Interestingly, translational activity from the 5'UTR of some of the HIV-1 variants was enhanced relative to that observed for the 5'UTR of pNL4.3. In an attempt to explain these findings we probed the secondary structure of the variant HIV-1 5'UTRs using enzymatic and chemical approaches. Yet subsequent structural analyses did not reveal significant variations when compared to the pNL4.3-5'UTR. Thus, the increased IRES-activity observed for some of the HIV-1 variants cannot be ascribed to a specific structural modification. A model to explain these findings is proposed.
- ItemGenetic variations in host IL28B links to the detection of peripheral blood mononuclear cells-associated hepatitis C virus RNA in chronically infected patients(2013) Angulo, Jenniffer; Pino, Karla; Pavez, C.; Biel, F.; Labbé, Pilar; Miquel P., Juan Francisco; Soza, Alejandro; López Lastra, Marcelo Andrés
- ItemInfection of human monocyte-derived dendritic cells by ANDES Hantavirus enhances pro-inflammatory state, the secretion of active MMP-9 and indirectly enhances endothelial permeability(2011) Marsac, Delphine; García, Stephanie; Pino, Karla; Ferrés Garrido, Marcela Viviana; López Lastra, Marcelo Andrés; Kalergis Parra, Alexis Mikes; Fournet, Alexandra; Aguirre, Adam; Veas, FranciscoAbstract Background Andes virus (ANDV), a rodent-borne Hantavirus, is the major etiological agent of Hantavirus cardiopulmonary syndrome (HCPS) in South America, which is mainly characterized by a vascular leakage with high rate of fatal outcomes for infected patients. Currently, neither specific therapy nor vaccines are available against this pathogen. ANDV infects both dendritic and epithelial cells, but in despite that the severity of the disease directly correlates with the viral RNA load, considerable evidence suggests that immune mechanisms rather than direct viral cytopathology are responsible for plasma leakage in HCPS. Here, we assessed the possible effect of soluble factors, induced in viral-activated DCs, on endothelial permeability. Activated immune cells, including DC, secrete gelatinolytic matrix metalloproteases (gMMP-2 and -9) that modulate the vascular permeability for their trafficking. Methods A clinical ANDES isolate was used to infect DC derived from primary PBMC. Maturation and pro-inflammatory phenotypes of ANDES-infected DC were assessed by studying the expression of receptors, cytokines and active gMMP-9, as well as some of their functional status. The ANDES-infected DC supernatants were assessed for their capacity to enhance a monolayer endothelial permeability using primary human vascular endothelial cells (HUVEC). Results Here, we show that in vitro primary DCs infected by a clinical isolate of ANDV shed virus RNA and proteins, suggesting a competent viral replication in these cells. Moreover, this infection induces an enhanced expression of soluble pro-inflammatory factors, including TNF-α and the active gMMP-9, as well as a decreased expression of anti-inflammatory cytokines, such as IL-10 and TGF-β. These viral activated cells are less sensitive to apoptosis. Moreover, supernatants from ANDV-infected DCs were able to indirectly enhance the permeability of a monolayer of primary HUVEC. Conclusions Primary human DCs, that are primarily targeted by hantaviruses can productively be infected by ANDV and subsequently induce direct effects favoring a proinflammatory phenotype of infected DCs. Finally, based on our observations, we hypothesize that soluble factors secreted in ANDV-infected DC supernatants, importantly contribute to the endothelial permeability enhancement that characterize the HCPS.
- ItemNon-canonical translation initiation of the spliced mRNA encoding the human T-cell leukemia virus type 1 basic leucine zipper protein(2018) Cáceres, C. Joaquín; Angulo, Jenniffer; Lowy de la Torre, Fernando; Contreras, Nataly; Walters, Beth; Olivares, Eduardo; Allouche, Delphine; Merviel, Anne; Pino, Karla; Sargueil, Bruno; Thompson, Sunnie R.; López Lastra, Marcelo Andrés
- ItemPolypyrimidine tract-binding protein binds to the 5' untranslated region of the mouse mammary tumor virus mRNA. and stimulates cap-independent translation initiation(2016) Cáceres, Carlos J.; Contreras, Nataly; Angulo, Jenniffer; Vera Otarola, Jorge; Pino Ajenjo, Constanza; Llorian, Miriam; Ameur, Melissa; Lisboa, Francisco; Pino, Karla; López Lastra, Marcelo Andrés; Lowy de la Torre, Fernando; Sargueil, Bruno
- ItemStructural domains within the HIV-1 mRNA. and the ribosomal protein S25 influence cap-independent translation initiation(2016) Carvajal, Felipe; Vallejos, Maricarmen; Walters, Beth; Contreras, Nataly; Hertz, Marla I.; Olivares, Eduardo; Cáceres, Carlos J.; Pino, Karla; Letelier, Alejandro; López Lastra, Marcelo Andrés; Thompson, Sunnie R.
- ItemTargeting deoxyhypusine hydroxylase activity impairs cap-independent translation initiation driven by the 5'untranslated region of the HIV-1, HTLV-1, and MMTV mRNAs(2016) Cáceres, C. Joaquín; Angulo, Jenniffer; Contreras, Nataly; Pino, Karla; Vera Otarola, Jorge; López Lastra, Marcelo Andrés
- ItemThe Andes Hantavirus NSs Protein Is Expressed from the Viral Small mRNA by a Leaky Scanning Mechanism(AMER SOC MICROBIOLOGY, 2012) Vera Otarola, Jorge; Solis, Loretto; Soto Rifo, Ricardo; Ricci, Emiliano P.; Pino, Karla; Tischler, Nicole D.; Ohlmann, Theophile; Darlix, Jean Luc; Lopez Lastra, MarceloThe small mRNA (SmRNA) of all Bunyaviridae encodes the nucleocapsid (N) protein. In 4 out of 5 genera in the Bunyaviridae, the smRNA encodes an additional nonstructural protein denominated NSs. In this study, we show that Andes hantavirus (ANDV) SmRNA encodes an NSs protein. Data show that the NSs protein is expressed in the context of an ANDV infection. Additionally, our results suggest that translation initiation from the NSs initiation codon is mediated by ribosomal subunits that have bypassed the upstream N protein initiation codon through a leaky scanning mechanism.
- ItemThe Elav-like protein HuR exerts translational control of viral internal ribosome entry sites(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2009) Rivas Aravena, Andrea; Ramdohr, Pablo; Vallejos, Maricarmen; Valiente Echeverria, Fernando; Dormoy Raclet, Virginie; Rodriguez, Felipe; Pino, Karla; Holzmann, Cristian; Huidobro Toro, J. Pablo; Gallouzi, Imed Eddine; Lopez Lastra, MarceloThe human embryonic-lethal abnormal vision (ELAV)-like protein. HuR, has been recently found to be involved in the regulation of protein synthesis. In this study we show that HuR participates in the translational control of the HIV-1 and HCV IRES elements. HuR functions as a repressor of HIV-1]RES activity and acts as an activator of the HCV]RES. The effect of HuR was evaluated in three independent experimental systems, rabbit reticulocyte lysate, HeLa cells, and Xenopus laevis oocytes, using both overexpression and knockdown approaches. Furthermore, results suggest that HuR mediated regulation of HIV-1 and HCV IRESes does not require direct binding of the protein to the RNA nor does it need the nuclear translocation of the IRES-containing RNAs. Finally, we show that HuR has a negative impact on post-integration steps of the HIV-1 replication cycle. Thus, our observations yield novel insights into the role of HuR in the post-transcriptional regulation of HCV and HIV-1 gene expression. (C) 2009 Elsevier Inc. All rights reserved.
- ItemUrinary leukotriene and Bcl I polymorphism of glucocorticoid receptor gene in preschoolers with recurrent wheezing and high risk of asthma(2016) Morales, M.; Flores, C.; Pino, Karla; Angulo, J.; López Lastra, Marcelo Andrés; Castro Rodríguez, José Antonio