Marcelo López‐Lastra

ORCID: 0000-0002-7936-8478
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About
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Research Areas
  • Viral Infections and Immunology Research
  • RNA and protein synthesis mechanisms
  • Hepatitis C virus research
  • RNA Research and Splicing
  • Viral Infections and Vectors
  • HIV Research and Treatment
  • Liver Disease Diagnosis and Treatment
  • Mosquito-borne diseases and control
  • Viral Infections and Outbreaks Research
  • Virus-based gene therapy research
  • RNA regulation and disease
  • Hepatitis B Virus Studies
  • T-cell and Retrovirus Studies
  • RNA Interference and Gene Delivery
  • CRISPR and Genetic Engineering
  • Viral gastroenteritis research and epidemiology
  • Plant Virus Research Studies
  • Systemic Lupus Erythematosus Research
  • Fire effects on ecosystems
  • Animal Disease Management and Epidemiology
  • RNA modifications and cancer
  • Vector-Borne Animal Diseases
  • Cytokine Signaling Pathways and Interactions
  • HIV/AIDS drug development and treatment
  • Animal Virus Infections Studies

Pontificia Universidad Católica de Chile
2014-2024

Millennium Institute on Immunology and Immunotherapy
2011-2017

Instituto de Hematología e Inmunología
2015

Medicina
2014

Centro de Investigaciones Cardiovasculares
2014

University of Colorado Denver
2011

Universidad Andrés Bello
2009

University of Chile
1994-2008

McGill University
2002-2003

Inserm
1997-2001

ABSTRACT The 5′ leader of the human immunodeficiency virus type 1 (HIV-1) genomic RNA contains highly structured domains involved in key steps viral life cycle. These inhibit cap-dependent protein synthesis. Here we report that HIV-1 harbors an internal ribosome entry site (IRES) capable driving synthesis during G 2 /M cell cycle phase which initiation is inhibited. IRES was delineated with bicistronic mRNAs vitro and ex vivo assays. spans nucleotides 104 to 336 partially overlaps major...

10.1128/jvi.77.7.3939-3949.2003 article EN Journal of Virology 2003-03-12

Human immunodeficiency virus type 1 (HIV-1) co-opts host proteins and cellular machineries to its advantage at every step of the replication cycle. Here we show that HIV-1 enhances heterogeneous nuclear ribonucleoprotein (hnRNP) A1 expression promotes relocalization hnRNP cytoplasm. The latter was dependent on export unspliced viral genomic RNA (vRNA) alterations in abundance localization FG-repeat pore glycoprotein p62. vRNA remain colocalized cytoplasm supporting a post-nuclear function...

10.1074/jbc.m109.048736 article EN cc-by Journal of Biological Chemistry 2009-09-09

Abstract Translation initiation of the human immunodeficiency virus-type 1 (HIV-1) genomic mRNA (vRNA) is cap-dependent or mediated by an internal ribosome entry site (IRES). The HIV-1 IRES requires IRES-transacting factors (ITAFs) for function. In this study, we evaluated role heterogeneous nuclear ribonucleoprotein K (hnRNPK) as a potential ITAF IRES. HIV-1-expressing cells, depletion hnRNPK reduced vRNA translation. Furthermore, both and overexpression modulated activity. Phosphorylations...

10.1093/nar/gkad1221 article EN cc-by Nucleic Acids Research 2024-01-02

The 5′ leader of the human immunodeficiency virus type 1 (HIV-1) genomic RNA harbors an internal ribosome entry site (IRES) that is functional during G2/M phase cell cycle. Here we show translation initiation mediated by HIV-1 IRES requires participation trans-acting cellular factors other than canonical translational machinery. We used 'standard' chemical and enzymatic probes 'RNA SHAPE' analysis to model structure show, means a footprinting assay, extracts provide protections regions...

10.1093/nar/gkr189 article EN cc-by-nc Nucleic Acids Research 2011-04-10

A hepatitis outbreak has occurred in Chile since November 2016. Men are predominantly affected, with a large proportion of men who have sex (MSM). We describe 12 consecutive unrelated confirmed cases presented at our healthcare institution Santiago Metropolitan Area. Nine were men, all reporting having had men. Ten viral sequences, genotyped as IA, clustered the V16-25801 strain causing outbreaks mostly MSM Europe mid-2016.

10.2807/1560-7917.es.2018.23.9.18-00060 article EN cc-by Eurosurveillance 2018-03-01

The small mRNA (SmRNA) of all Bunyaviridae encodes the nucleocapsid (N) protein. In 4 out 5 genera in Bunyaviridae, smRNA an additional nonstructural protein denominated NSs. this study, we show that Andes hantavirus (ANDV) SmRNA NSs Data is expressed context ANDV infection. Additionally, our results suggest translation initiation from codon mediated by ribosomal subunits have bypassed upstream N through a leaky scanning mechanism.

10.1128/jvi.06223-11 article EN Journal of Virology 2011-12-08

The precursor group-specific antigen (pr55Gag) is central to HIV-1 assembly. Its expression alone sufficient assemble into virus-like particles. It also selects the genomic RNA for encapsidation and involved in several important virus-host interactions viral assembly restriction, making its synthesis essential aspects of replication. Here, we show that initiation translation mediated through both a cap-dependent an internal ribosome entry site (IRES)-mediated mechanisms. In support this...

10.1371/journal.pone.0068108 article EN cc-by PLoS ONE 2013-07-05

The retroviral genomic RNA is the messenger for synthesis of group-specific antigen (gag) and polymerase precursors major structural proteins enzymes virion. 5′-untranslated leader simian immunodeficiency virus (SIV) formed highly structured domains involved in key steps viral life cycle. Thus, presence stable structures between 5′-cap gag start codon are thought to strongly inhibit scanning a 43 S preinitiation ribosomal complex. This prompted us look an alternative canonical ribosome...

10.1074/jbc.275.16.11899 article EN cc-by Journal of Biological Chemistry 2000-04-01

The murine leukemia virus (MLV)-related type C viruses constitute a major class of retroviruses that includes numerous endogenous and exogenous mammalian the related avian spleen necrosis (SNV). MLV-related possess long multifunctional 5′ untranslated leader involved in key steps viral life cycle—splicing, translation, RNA dimerization, encapsidation, reverse transcription. Recent studies have shown Friend Moloney can direct cap independent translation gag precursor proteins (Berlioz et al.,...

10.1089/hum.1997.8.16-1855 article EN Human Gene Therapy 1997-11-01

The HCV internal ribosome entry site (IRES) spans a region of ∼340 nt that encompasses most the 5′ untranslated (5′UTR) viral mRNA and first 24–40 core-coding region. To investigate implication altering primary sequence 5′UTR on IRES activity, naturally occurring variants were isolated from clinical samples analyzed. impact identified mutations translation was evaluated in context RLuc/FLuc bicistronic RNAs. Results show depending their location within RNA structure, these cause range...

10.1093/nar/gkn1022 article EN cc-by-nc Nucleic Acids Research 2008-12-23

Abstract Background The human immunodeficiency virus type 1 (HIV-1) Tat protein is a major viral transactivator required for HIV-1 replication. In the nucleus greatly stimulates synthesis of full-length transcripts from promoter by causing efficient transcriptional elongation. induces elongation directly interacting with bulge transactivation response (TAR) RNA, hairpin-loop located at 5'-end all nascent transcripts, and recruiting cellular co-activators. cytoplasm, thought to act as...

10.1186/1742-4690-6-74 article EN cc-by Retrovirology 2009-08-11

ABSTRACT Hantavirus cardiopulmonary syndrome (HCPS) is a highly pathogenic emerging disease (40% case fatality rate) caused by New World hantaviruses. infections are transmitted to humans mainly inhalation of virus-contaminated aerosol particles rodent excreta and secretions. At present, there no antiviral drugs or immunotherapeutic agents available for the treatment hantaviral infection, survival rates infected patients hinge largely on early virus recognition hospital admission aggressive...

10.1128/jvi.02409-08 article EN Journal of Virology 2009-03-12

The 5′untranslated regions (UTR) of the full length mRNA HIV-1 proviral clones pNL4.3 and pLAI, harbor an internal ribosomal entry site (IRES). In this study we extend finding by demonstrating that 5′UTRs natural variants also exhibit IRES-activity. Cap-independent translational activity was demonstrated using bicistronic mRNAs in HeLa cells Xenopus laevis oocytes. possibility expression downstream cistron these constructs due to alternative splicing or cryptic promoter ruled out. exhibited...

10.1371/journal.pone.0035031 article EN cc-by PLoS ONE 2012-04-04

Abstract Background Andes virus (ANDV), a rodent-borne Hantavirus, is the major etiological agent of Hantavirus cardiopulmonary syndrome (HCPS) in South America, which mainly characterized by vascular leakage with high rate fatal outcomes for infected patients. Currently, neither specific therapy nor vaccines are available against this pathogen. ANDV infects both dendritic and epithelial cells, but despite that severity disease directly correlates viral RNA load, considerable evidence...

10.1186/1743-422x-8-223 article EN cc-by Virology Journal 2011-05-13

Andes virus (ANDV) is the etiological agent of hantavirus cardiopulmonary syndrome in Chile. In this study, we evaluated profile pro-inflammatory cytokines IL-1β, IL-12p70, IL-21, TNF-α, IFN-γ, IL-10 and IL-6 serum samples ANDV-infected patients at time hospitalization. The mean levels circulating were determined by a Bead-Based Multiplex assay coupled with Luminex detection technology, order to compare 43 healthy controls that had been categorized according severity disease. When compared...

10.1371/journal.pntd.0005757 article EN cc-by PLoS neglected tropical diseases 2017-07-14

As obligatory intracellular parasites, viruses rely on cellular machines to complete their life cycle, and most importantly they recruit the host ribosomes translate mRNA. The Hepatitis C viral mRNA initiates translation by directly binding 40S ribosomal subunit in such a way that initiation codon is correctly positioned P site of ribosome. Such property likely be central for many viruses, therefore description host-pathogen interaction at molecular level instrumental provide new therapeutic...

10.1093/nar/gkv1325 article EN cc-by Nucleic Acids Research 2015-11-30

The 5' leader of the HIV-1 genomic RNA is a multifunctional region that folds into secondary/tertiary structures regulate multiple processes during viral replication including translation initiation. In this work, we examine internal ribosome entry site (IRES) located in drives initiation Gag protein under conditions hinder cap-dependent We show activity IRES relies on ribosomal S25 (eS25). Additionally, mechanistic and mutational analysis revealed modular nature once 40S subunit recruited...

10.1111/febs.13756 article EN FEBS Journal 2016-05-18

ABSTRACT The human T-cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that causes adult T cell and of HTLV-associated myelopathy/tropical spastic paraparesis. mRNA some retroviruses, including the simian immunodeficiency viruses (HIV SIV), can initiate translation using canonical cap-dependent mechanism or through an internal ribosome entry site (IRES). In this study, we present strong evidence showing like HIV-1 SIV, 5′-untranslated region (5′UTR) HTLV-1 full-length harbors IRES....

10.1128/jvi.00279-14 article EN Journal of Virology 2014-03-13

Abstract Background Vitamin D deficiency and single nucleotide polymorphisms ( SNP ) in the gene encoding vitamin receptor VDR have been associated with asthma. Objective To compare 25‐hydroxyvitamin (25 OHD levels frequency of 3 s between asthmatic healthy children. Methods In persistent control children, 25 were measured using radioimmunoassay (FokI, ApaI, TaqI) analyzed by a PCR ‐ RFLP assay. Relevant medical history was collected. Results About 75 (median age: 9.1 years) 227 children...

10.1111/pai.12409 article EN Pediatric Allergy and Immunology 2015-05-22
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