RETROVIROLOGIA I ESTUDIS CLíNICS (GREC)

Investigador Principal: Javier Martínez-Picado

Presentació

El nostre grup centra el seu interès en estudis translacionals de la infecció pel VIH-1 i en la recerca de noves estratègies terapèutiques contra el VIH/sida mitjançant la combinació de recerca bàsica i aplicada. Amb aquest objectiu, treballem en estreta col·laboració amb la unitat clínica de VIH de l’Hospital Universitari Germans Trias i Pujol, que atén més de 2.000 persones amb aquesta infecció. Els seus programes de recerca se centren en quatre àrees prioritàries:

1) Eradicació del VIH. Avaluem la persistència de la replicació en presència d’un tractament antiretroviral efectiu, estudiem la localització dels reservoris virals i les seves conseqüències, i treballem en estudis clínics enfocats al desenvolupament d’intervencions terapèutiques destinades a la reducció d’aquests reservoris i a l’eradicació de la malaltia. A més, el nostre grup lidera el primer consorci de trasplantament al·logènic amb cèl·lules mare en pacients amb VIH (IciStem), opció que pot implicar un gran avenç en aquest àmbit.

2) Patogènesi del VIH mitjançada per cèl·lules dendrítiques. Ens basem en el nostre descobriment de l’eix de reconeixement entre gangliòsids virals i el seu receptor SIGLEC-1, com també en el seu paper en la transinfecció i en el disseny d’estratègies terapèutiques que puguin aprofitar aquest mecanisme.

3) Fenotips extrems de la infecció per VIH (progressió ràpida, controladors espontanis, virèmics no progressors i exposats no infectats). Avaluem les característiques immunovirològiques implicades en aquests perfils que puguin contribuir al coneixement de la patogènesi de la infecció i la seva aplicació en noves estratègies terapèutiques, diagnòstiques i de seguiment personalitzat dels pacients.

4) Noves estratègies terapèutiques. Ens centrem especialment en tractaments antiretrovirals i immunoteràpies, els mecanismes d’emergència de resistències a aquests i les seves repercussions en el fitness viral.

Llegeix més

Paraules clau: immunopatogènesi, cura/eradicació, persistència viral, reservori, cèl·lules mieloides, transinfecció, progressió

Investigador Principal

Javier Martínez-Picado

Javier Martínez-Picado és investigador de l’Institut Català de Recerca i Estudis Avançats (ICREA) a IrsiCaixa i professor associat de la Universitat de Vic (UVic). Es va doctorar a la Universitat de Barcelona, on posteriorment va esdevenir professor associat i impartia...

Currículum

Línies estratègiques

Línies de recerca

Eradicació del VIH
Patogènesi del VIH-1 mitjançada per cèl·lules mieloides
Fenotips extrems de la infecció per VIH

Projectes

Allogeneic Stem Cell Transplantation in HIV-1 Infected Individuals (IciStem)

Data: 01/10/2015 - 28/02/2017 Investigadors/es principals: Javier Martínez-Picado, Annemarie Wensing (University Medical Center Utrecht)

HIV Reservoir Dynamics After Switching to Dolutegravir in Patients on a PI/r Based Regimen. A Phase IV Open Randomized Trial

Data: 01/01/2015 - 31/12/2017 Investigadors/es principals: Javier Martínez-Picado, Manel Crespo (Hospital Universitari de la Vall d’Hebron)

Novel therapeutic agents to block interactions between enveloped viruses and myeloid cells: combating the settlement of infections (BLOCKER-PRO)

Data: 01/01/2017 – 31/12/2019 Investigadors/es principals: Javier Martínez-Picado, Nuria Izquierdo-Useros

New genetic engineering tools for the treatment of AIDS "STOP-AIDS"

Data: 01/04/2016 – 31/12/2019 Investigadors/es principals: Javier Martínez-Picado

DURVAST: A phase II exploratory study of durvalumab (MEDI4736) in HIV-1 patients with advanced solid tumors

Data: 01/01/2017 – 31/12/2019 Investigadors/es principals: Javier Martínez-Picado

Non-invasive viral reservoir characterization in Lymph Nodes through Fine Needle Biopsies in patients with distinct HIV progression profiles

Data: 01/01/2017 – 31/12/2019 Investigadors/es principals: Javier Martínez-Picado

Low Viral Reservoir in treated Subjects (LoViReT). Predictors of Extremely Low HIV-1 DNA Reservoir in Subjects Initiating cART during Chronic Infection

Data: 01/09/2016 – 30/08/2017 Investigadors/es principals: Javier Martínez-Picado

Glicoingeniería de nanovehículos para eliminar los reservorios virales; saf2017-91767-exp

Data: Gener 2019 - Gener 2021 Investigadors/es principals: Nuria Izquierdo-Useros

Allogeneic stem cell transplantation in HIV-1 infected individuals and 1st ITATI strategy

Data: 2018 - 2020 Investigadors/es principals: Javier Martínez-Picado

Treatment with immunological checkpoint inhibitors of HIV-infected subjects with cancer

Data: 2018 - 2023 Investigadors/es principals: Javier Martínez-Picado

Characterisation of single molecule dynamics within HIV-1 reservoirs as a target for interference with virus persistence and immune evasion

Data: a:6:{s:16:"ckeditor_default";s:1:"t";s:20:"ckeditor_show_toggle";s:1:"t";s:14:"ckeditor_width";s:4:"100%";s:13:"ckeditor_lang";s:2:"en";s:18:"ckeditor_auto_lang";s:1:"t";s:7:"contact";i:1;} Investigadors/es principals: Javier Martínez-Picado, Jakub Chojnacki

SIGTECH - New technologies mimicking virus-cell interaction to fight infectious diseases

Data: 2018 - 2023 Investigadors/es principals: Javier Martínez-Picado, Nuria Izquierdo-Useros

VIROCURE - Cutting edge strategies on HIV cure

Data: 2018 - 2023 Investigadors/es principals: Javier Martínez-Picado

Exploratory, open-label, randomized clinical trial to assess the efficacy of first-line dual vs. triple antiretroviral therapy in HIV-1 reservoir and in peripheral compartments in HIV-infected patients

Data: 01/07/2019 - 30/06/2021 Investigadors/es principals: Javier Martínez-Picado, José Moltó

Glycoengineering nanovehicles to purge viral reservoirs

Data: 1/2018 – 11/2020 Investigadors/es principals: Nuria Izquierdo-Useros

Publicacions

Methylation regulation of antiviral host factors, Interferon Stimulated Genes (ISGs) and T-cell responses associated with natural HIV control

Revista: PLOS Pathogens Any: 2020

HIVconsv vaccines and romidepsin in early-treated HIV-1-infected individuals: safety, immunogenicity and effect on the viral reservoir (Study BCN02)

Revista: Frontiers in Immunology Any: 2020

Vulnerability to reservoir reseeding due to high immune activation after allogeneic hematopoietic stem cell transplantation in individuals with HIV-1

Revista: Science Translational Medicine Any: 2020

A minor population of macrophage-tropic HIV-1 variants is identified in recrudescing viremia following analytic treatment interruptio

Revista: PNAS Any: 2020

Sex-specific innate immune selection of HIV-1in utero is associated with increased femalesusceptibility to infection

Revista: Nature Communications Any: 2020

When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses

Revista: Viruses Any: 2019

Enhancement of antiviral CD8+ T-cell responses and complete remission of metastatic melanoma in an HIV-1-infected subject treated with pembrolizumab

Revista: Journal of Clinical Medicine Any: 2019

Switching from a protease inhibitor-based regimen to a dolutegravir-based regimen: a randomized clinical trial to determine the effect on peripheral blood and ileum biopsies from ART-suppressed HIV-infected individuals

Revista: Clinical Infectious Diseases Any: 2019

Therapeutic Vaccine in Chronically HIV-1-Infected Patients: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Trial with HTI-TriMix

Revista: Vaccines Any: 2019

HIV-1 Gag specifically restricts PI(4,5)P2 and cholesterol mobility in living cells creating a nanodomain platform for virus assembly

Revista: Science Advances Any: 2019

Dasatinib protects humanized mice from acute HIV-1 infection

Any: 2019

Increasing diagnostic uncertainties in children with in utero HIV infection

Revista: The Pediatric Infectious Disease Journal Any: 2019

Therapeutic Vaccination Refocuses T-cell Responses Towards Conserved Regions of HIV-1 in Early Treated Individuals

Revista: EClinicalMedicine Any: 2019

Anti-Siglec-1 antibodies block Ebola viral uptake and decrease cytoplasmic viral entry

Revista: Nature Microbiology Any: 2019

Dendritic cells from the cervical mucosa capture and transfer HIV-1 via Siglec-1

Revista: Frontiers in Immunology Any: 2019

Recommendations for analytical antiretroviral treatment interruptions in HIV research trials-report of a consensus meeting

Revista: Lancet HIV Any: 2019

HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation

Revista: Nature Any: 2019

Detailed Characterization of Early HIV-1 Replication Dynamics in Primary Human Macrophages

Revista: Viruses Any: 2018

Cancer immunotherapy of patients with HIV infection

Revista: Clinical and Translational Oncology Any: 2018

Phase I clinical trial of an intranodally administered mRNA based therapeutic vaccine against HIV-1 infection

Revista: AIDS Any: 2018

Mechanisms That Contribute to a Profound Reduction of the HIV-1 Reservoir After Allogeneic Stem Cell Transplant

Revista: Annals of Internal Medicine Any: 2018

. Long-term remission despite clonal expansion of replication-competent HIV-1 isolates

Revista: JCI Insight Any: 2018

Proteomics study of human cord blood reticulocyte-derived exosomes

Revista: Scientific Reports Any: 2018

The Mathilde Krim effect as a way to overcome the Matilda effect

Revista: AIDS Research and Human Retroviruses Any: 2018

Plasma EBV-load as an early biomarker and prognostic factor of HIV-related lymphomas

Revista: Clinical Infectious Diseases Any: 2018

CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells

Revista: Science Translational Medicine Any: 2018

Impact of intensification with raltegravir on HIV-1-infected individuals receiving monotherapy with boosted PIs

Revista: Journal of Antimicrobial Chemotherapy Any: 2018

Control of HIV-1 pathogenesis in viremic nonprogressors is independent of Gag-specific CTL responses

Revista: Journal of Virology Any: 2018

Episomal HIV‑1 DNA and its relationship to other markers of HIV‑1 persistence

Revista: Retrovirology Any: 2018

Differential immunodominance hierarchy of CD8+ T cell responses in HLA-B27:05 and B27:02-mediated control of HIV-1 infection

Revista: Journal of Virology Any: 2017

Retroviruses As Myeloid Cell Riders: What Natural Human Siglec-1 “Knockouts” Tell Us About Pathogenesis

Revista: Frontiers in Immunology Any: 2017

Virological and immunological outcome of treatment interruption in HIV-1-infected subjects vaccinated with MVA-B

Revista: PLOS ONE Any: 2017

Identification of Interleukin-27 (IL-27)/IL-27 Receptor Subunit Alpha as a Critical Immune Axis for In Vivo HIV Control

Revista: Journal of Virology Any: 2017

Gag-protease coevolution analyses define novel structural surfaces in the HIV-1 matrix and capsid involved in resistance to Protease Inhibitors

Revista: Scientific Reports Any: 2017

Identification of IL-27/IL-27RA as a critical immune axis for in vivo HIV control

Revista: Journal of Virology Any: 2017

Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects

Revista: Journal of the International AIDS Society Any: 2017

Sensitive Quantification of the HIV-1 Reservoir in Gut-Associated Lymphoid Tissue

Revista: PLOS ONE Any: 2017

Response to "Tenofovir Disoproxil Fumarate Is Not an Inhibitor of Human Organic Cation Transporter 1"

Revista: The Journal of Pharmacology and Experimental Therapeutics Any: 2017

Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif

Revista: Scientific Reports Any: 2017

Relationship between CCR5(Δ32/WT) Heterozygosity and HIV-1 Reservoir Size in Adolescents and Young Adults with Perinatally Acquired HIV-1 Infection

Revista: Clinical Microbiology and Infection Any: 2016

Identification of Siglec-1 null individuals infected with HIV-1

Revista: Nature Communications Any: 2016

Lack of concordance between residual viremia and viral variants driving de novo infection of CD4(+) T cells on ART

Revista: Retrovirology Any: 2016

Non-human TRIM5 variants enhance recognition of HIV-1-infected cells by CD8+ T cells

Revista: Journal of Virology Any: 2016

Persistent HIV-1 replication during antiretroviral therapy

Revista: Current Opinion in HIV and AIDS Any: 2016

Long-Term Spontaneous Control of HIV-1 Is Related to Low Frequency of Infected Cells and Inefficient Viral Reactivation

Revista: Journal of Virology Any: 2016

Epstein-Barr viral loads and serum free light chains levels are potential follow-up markers of HIV-related lymphomas

Revista: Leukemia & Lymphoma Any: 2016

Short-term Treatment With Interferon Alfa Diminishes Expression of HIV-1 and Reduces CD4+ T-Cell Activation in P

Revista: Journal of Infectious Diseases Any: 2016

Does rapid HIV disease progression prior to combination antiretroviral therapy hinder optimal CD4+ T-cell recovery once HIV-1 suppression is achieved?

Revista: AIDS Any: 2015

Establishment and replenishment of the viral reservoir in perinatally HIV-1-infected children initiating very early antiretroviral therapy

Revista: Clinical Infectious Diseases Any: 2015

Mouse Siglec-1 mediates trans-infection of surface-bound murine leukemia virus in a sialic acid N-acyl side chain-dependent manner

Revista: Journal of Biological Chemistry Any: 2015

CCR5 Δ32 homozygous cord blod allogeneic transplantation in a patient with HIV: a case report

Revista: Lancet HIV Any: 2015

HIV-1 immune activation induces Siglec-1 expression and enhances viral trans-infection in blood and tissue myeloid cells

Revista: Retrovirology Any: 2015

Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load

Revista: PNAS Any: 2015

Safety and immunogenicity of a modified vaccinia Ankara-based HIV-1 vaccine (MVA-B) in HIV-1-infected patients alone or in combination with a drug to reactivate latent HIV-1

Revista: Journal of Antimicrobial Chemotherapy Any: 2015

Different Plasma Markers of Inflammation Are Influenced by Immune Recovery and cART Composition or Intensification in Treated HIV Infected Individuals

Revista: PLOS ONE Any: 2014

Highly pathogenic adapted HIV-1 strains limit host immunity and dictate rapid disease progression

Revista: AIDS Any: 2014

HIV-1 Capture and Transmission by Dendritic Cells: The Role of Viral Glycolipids and the Cellular Receptor Siglec-1

Revista: PLOS Pathogens Any: 2014

Intensification of a raltegravir-based regimen with maraviroc in early HIV-1 infection

Revista: AIDS Any: 2014

Effect of lithium on HIV-1 expression and proviral reservoir size in the CD4+ T cells of antiretroviral therapy suppressed patients

Revista: AIDS Any: 2014

Actin-binding protein drebrin regulates HIV-1-triggered actin polymerization and viral infection

Revista: The Journal of Biological Chemistry Any: 2013

The infectious synapse formed between mature dendritic cells and CD4(+) T cells is independent of the presence of the HIV-1 envelope glycoprotein

Revista: Retrovirology Any: 2013

A dendritic cell-based vaccine elicits T-cell responses associated with a significant control of HIV-1 replication

Revista: Science Translational Medicine Any: 2013

Assessing main death pathways in T lymphocytes from HIV infected individuals

Revista: Cytometry Part A Any: 2013

A non-infectious cell-based phenotypic assay for the assessment of HIV-1 susceptibility to protease inhibitors

Revista: Journal of Antimicrobial Chemotherapy Any: 2012

Dynamic Imaging of Cell-Free and Cell-Associated Viral Capture in Mature Dendritic Cells

Revista: Traffic Any: 2012

Novel two-round phenotypic assay for protease inhibitor susceptibility testing in recombinant and primary HIV-1 isolates

Revista: Journal of Clinical Microbiology Any: 2012

HIV-1 capture and antigen presentation by dendritic cells: enhanced viral capture does not correlate with better T-cell activation

Revista: The Journal of Immunology Any: 2012

The PDZ-adaptor protein syntenin-1 regulates HIV-1 entry

Revista: Molecular Biology of the Cell Any: 2012

Sialyllactose in Viral Membrane Gangliosides Is a Novel Molecular Recognition Pattern for Mature Dendritic Cell Capture of HIV-1

Revista: PLOS Biology Any: 2012

In-depth characterization of viral isolates from plasma and cells compared with plasma circulating quasispecies in early HIV-1 infection

Revista: PLOS One Any: 2012

Capture of cell-derived microvesicles (exosomes and apoptotic bodies) by human plasmacytoid dendritic cells

Revista: Journal of Leukocyte Biology Any: 2012

Siglec-1 Is a Novel Dendritic Cell Receptor That Mediates HIV-1 Trans-Infection Through Recognition of Viral Membrane Gangliosides

Revista: PLOS Biology Any: 2012

Definition of the viral targets of protective HIV-1-specific T cell responses

Revista: Journal of Translational Medicine Any: 2011

Deep Molecular Characterization of HIV-1 Dynamics under Suppressive HAART

Revista: PLOS Pathogens Any: 2011

Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque

Revista: The Journal of Clinical Investigation Any: 2011

Exosomes and retroviruses: the chicken or the egg?

Revista: Cellular Microbiology Any: 2010

Dihydrosphingomyelin impairs HIV-1 infection by rigidifying liquid-ordered membrane domains

Revista: Chemistry & Biology Any: 2010

HIV and Mature Dendritic Cells: Trojan Exosomes Riding the Trojan Horse?

Revista: PLOS Pathogens Any: 2010

HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects

Revista: Nature Medicine Any: 2010

The HIV-1 integrase genotype strongly predicts raltegravir susceptibility but not viral fitness of primary virus isolates.

Revista: AIDS Any: 2010

HIV-1 and Mature Dendritic cells: Trojan exosomes riding the Trojan horse?

Revista: PLOS Pathogens Any: 2010

Capture and transfer of HIV-1 particles by mature dendritic cells converges with the exosome-dissemination pathway

Revista: Blood Any: 2009

Contribution of immunological and virological factors to extremely severe primary HIV type 1 infection.

Revista: Clinical Infectious Diseases Any: 2009

HIV transfer between CD4 T cells does not require LFA-1 binding to ICAM-1 and is governed by the interaction of HIV envelope glycoprotein with CD4

Revista: Retrovirology Any: 2008

A multidisciplinary approach for the identification of novel HIV-1 non-nucleoside reverse transcriptase inhibitors: S-DABOCs and DAVPs.

Revista: ChemMedChem Any: 2008

Expression and functionality of anti-human immunodeficiency virus and anticancer drug uptake transporters in immune cells

Revista: The Journal of Pharmacology and Experimental Therapeutics Any: 2007

Maturation of blood-derived dendritic cells enhances human immunodeficiency virus type 1 capture and transmission

Revista: Journal of Virology Any: 2007

AM3 modulates dendritic cell pathogen recognition capabilities by targeting DC-SIGN

Revista: Antimicrobial Agents and Chemotherapy Any: 2007

Evidence for preferential genotyping of a minority human immunodeficiency virus population due to primer-template mismatching during PCR-based amplification

Revista: Journal of Clinical Microbiology Any: 2005

Leukocyte Reduction Filters: an alternative source of Peripheral Blood Mononuclear Cells

Revista: Inmunología Any: 2003

Viral evolution during structured treatment interruptions in chronically human immunodeficiency virus-infected individuals

Esdeveniments

Col·laboració amb recerca clínica

Estudi obert de fase I per avaluar la seguretat i l’eficàcia de les vacunes HIVconsv administrades en combinació amb romidepsina en el control viral després de la interrupció del tractament antiretroviral en persones VIH positives tractades precoçment | BCN02-Romi

L’assaig clínic BCN02-Romi és un estudi d’eradicació que avaluarà l’eficàcia d’una estratègia de Kick & kill amb la utilització de les vacunes terapèutiques que s’han demostrat més immunogèniques fins ara (HIVconsv) en combina...

Estudi clínic observacional, per avaluar l’efecte dels trasplantaments al·logènics en pacients VIH-positius amb malalties hematològiques malignes | IciStem

Amb l’objectiu d’estudiar l’efecte dels transplantaments al·logènics en pacients infectats pel VIH que pateixen malalties hematològiques malignes, s’ha creat un consorci europeu co-liderat per IrsiCaixa. A dia d’avui s’han reclutat 17 ...

Estudi clínic observacional per avaluar els factors predictors de reservori viral extremadament baix | LoViReT

Estudi clínic observacional en què s’ha realitzat un screening de més de 400 pacients a nivell de DNA proviral a les seves cèl·lules amb l’objectiu de crear una cohort de 20-30 pacients amb un reservori extremadament baix. Un cop seleccionat...

Assaig clínic per avaluar l’efecte del durvalumab (MEDI4736) en pacients VIH-positius amb tumors sòlids avançats | Durvast

Assaig clínic en fase II per avaluar l’efecte del durvalumab (MEDI4736) en pacients VIH-positius amb tumors sòlids avançats. ...

An Open-Label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of ABX464 in HIV-1 Seronegative and Seropositive Adults | AbiVax 005

Clinical trial to evaluate the distribution of ABX464 and its main metabolite (N-Glu) in various compartments in HIV-1 Seronegative and Seropositive adult subjects. ...

Análisis de la presencia de virus infecciosos en la sangre de pacientes no progresores controladores de élite | LT-EC

Estudi clínic que pretén estudiar les característiques tant de l’hoste com del virus en pacients controladors d’èlit durant més de 10 anys, el qual ens pot permetre conèixer els mecanismes de control espontani de la infecció i profunditzar...

HIV adult and pediatric viremic non-progression: clues from immune preservation for the CURE | VNP

Estudi clínic que pretén estudiar els factors que contribueixen al fenotip dels virèmics no progressors, que mantenen un estat immunològic i general saludables, tot i tenir una elevada càrrega viral. ...