- HIV Research and Treatment
- Finance, Taxation, and Governance
- HIV/AIDS drug development and treatment
- Taxation and Legal Issues
- HIV/AIDS Research and Interventions
- Corporate Taxation and Avoidance
- Archaeological and Historical Studies
- Hepatitis C virus research
- Medieval Architecture and Archaeology
- Urbanism, Landscape, and Tourism Studies
- Historical Art and Architecture Studies
- Immune Cell Function and Interaction
- Historical Studies of Medieval Iberia
- Administrative Law and Governance
- Comparative International Legal Studies
- HIV-related health complications and treatments
- T-cell and Retrovirus Studies
- Medieval Iberian Studies
- Libraries, Manuscripts, and Books
- Medieval European Literature and History
- Blood groups and transfusion
- Spanish Literature and Culture Studies
- Social Sciences and Policies
- Latin American Legal and Economic Studies
- Medieval and Early Modern Iberia
Instituto de Salud Carlos III
2015-2024
Centro Nacional de Microbiologia
2012-2022
Hospital Universitario Fundación Jiménez Díaz
2018
Universidad Autónoma de Madrid
2018
Hospital Universitario de Getafe
2013
Hospital Universitario Puerta de Hierro Majadahonda
2012
Comunidad de Madrid
2000
Hospital Universitario Ramón y Cajal
1990
HIV-1 sequence diversity is affected by selection pressures arising from host genomic factors. Using paired human and viral data 1071 individuals, we ran >3000 genome-wide scans, testing for associations between DNA polymorphisms, variation plasma load (VL), while considering population structure. We observed significant SNP to a total of 48 amino acid variants (p<2.4 × 10(-12)). All associated SNPs mapped the HLA class I region. Clinical relevance pathogen was assessed using VL results....
ABSTRACT Muller’s ratchet predicts fitness losses in small populations of asexual organisms because the irreversible accumulation deleterious mutations and genetic drift. This effect should be enhanced if population bottlenecks intervene fixation is not compensated by recombination. To study whether could operate a retrovirus, 10 biological clones were derived from human immunodeficiency virus type 1 (HIV-1) field isolate MT-4 plaque assay. Each clone was subjected to 15 plaque-to-plaque...
Background Various patterns of HIV-1 disease progression are described in clinical practice and research. There is a need to assess the specificity commonly used definitions long term non-progressor (LTNP) elite controllers (LTNP-EC), viremic (LTNP-VC), non (LTNP-NC), as well chronic progressors (P) rapid (RP). Methodology Principal Findings We re-evaluated definitions, summarized Table 1, using information provided by selected number host genetic markers viral factors. continuous decrease...
ABSTRACT HIV-1 elite controllers (EC) maintain undetectable viral loads (VL) in the absence of antiretroviral treatment. However, these subjects have heterogeneous clinical outcomes, including a proportion that loses control over time. In this work, we compared, longitudinal design, transient EC, analyzed before and after loss virological control, with persistent EC. The aim was to identify factors leading natural infection retrospective study design. Gag-specific T-cell responses were...
Abstract Elite controllers (EC) represent a small subset of HIV-1-infected people that spontaneously control viral replication. However, natural virological suppression and absence immune dysfunction are not always long-term sustained. We define exceptional EC (EEC) as HIV-1 subjects who maintain the characteristics without disease progression for more than 25 years. analyzed three EEC, diagnosed between 1988 1992, never showed signs clinical in any antiretroviral treatment. A comprehensive...
A small group of HIV-1-infected individuals, called long-term nonprogressors (LTNPs), and in particular a subgroup LTNPs, elite controllers (LTNP-ECs), display permanent control viral replication lack clinical progression. This is the result complex interaction host, immune, factors. We identified, by phylogenetic analysis, cluster LTNP-ECs infected with very similar low-replication HIV-1 viruses, suggesting contribution common features to LTNP-EC phenotype. envelope (Env) glycoprotein...
Summary: To analyze superinfection in an HIV-1-infected patient showing high-risk practices, viral quasispecies were analyzed pol and env genes several plasma samples. Phylogenetic analysis the reverse transcriptase fragment gene identified a single virus first 3 samples analyzed, but 12 years after primoinfection, different strains detected quasispecies. This result suggests with 2 HIV-1 strains, one of which showed T215Y + M184V resistance mutations. The confirmed existence population,...
Although HIV-1 CRF12_BF and CRF38_BF are two epidemiologically important recombinant lineages circulating in Argentina Uruguay, little is known about their population dynamics. A total of 120 "CRF12_BF-like" 20 "CRF38_BF-like" pol sequences collected Uruguay from 1997 to 2009 were subjected phylogenetic Bayesian coalescent-based analyses estimate evolutionary demographic parameters. Phylogenetic revealed that viruses constitute a single epidemic with multiple genetic exchanges among...
Human immunodeficiency virus 1 (HIV-1) dual infections are considered important because they have been related to AIDS progression. We identified in 2 patients with long-term, nonprogressive HIV-1 disease; the first patient was diagnosed as being already coinfected, on basis of sample analyzed, but a previous superinfection could not be excluded; second having superinfection, 9-year difference between viral dating strains. Dual occur disease, no immediate clinical manifestations. Such...
Nevirapine-resistant variants were generated by serial passages in MT-2 cells the presence of increasing drug concentrations. In passage 5, mutations V106A, Y181C and G190A detected global population, associated with a 100-fold susceptibility decrease. Sequence analysis biological clones obtained from 5 subsequent showed that single mutants, first passages, progressively replaced 15 double correlating 500-fold increase phenotypic resistance. Fitness determination mutants confirmed that,...
Abstract sHLA are secreted by B and T lymphocytes upon activation. These antigens present in serum cerebrospinal fluid (CSF). The establishment of a index, IH = (CSF sHLA/serum sHLA)/(CSF albumin/serum albumin) helped us to define that values above 9.7 reflect an intrathecal synthesis these proteins. was significantly increased group patients with production IgG against HIV-1 (HIV) directly correlated the such antibodies. Therefore, seems be index lymphocyte activation CNS.
Background Fitness recovery of HIV-1 "in vitro" was studied using viral clones that had their fitness decreased as a result plaque-to-plaque passages. Principal Findings After ten large population passages, the populations showed an average increase fitness, although with wide variations among clones. While 5 significant increases, 3 increases were only marginally (p<0.1), and 4 did not show any change. accompanied by in p24 production, but associated titer. Few mutations (an 2 per genome)...
The transactive response DNA-binding protein (TARDBP/TDP-43) influences the processing of diverse transcripts, including that histone deacetylase 6 (HDAC6). Here, we assessed TDP-43 activity in terms regulating CD4+ T-cell permissivity to HIV-1 infection. We observed overexpression wt-TDP-43 increased both mRNA and levels HDAC6, resulting impaired infection independently viral envelope glycoprotein complex (Env) tropism. Consistently, using an Env-mediated cell-to-cell fusion model,...
Objective To study the causes for lack of clinical progression in a superinfected HIV-1 LTNP elite controller patient. Methodology and Principal Findings We studied host genetic, virological immunological factors associated with viral control SI long term non progressor (LTNP-EC). The individual contained both viruses maintained undetectable loads >20 years he did not express any described genetic polymorphisms control. None four full-length gp160 recombinants derived from LTNP-EC replicated...
Abstract In untreated HIV-1-infected individuals, viremia is positively associated with disease progression. However, some viremic non progressors (VNPs) individuals show paradoxical high CD4 + T cell counts. HIV-1 envelope glycoprotein complex (Env) a major cytopathic determinant in viral replication; therefore, we have deeply characterized Env function this rare clinical phenotype. Full-length clones isolated from Viral Load (VL) > 10,000 copies/mL classified as VNPs (n = 15) or rapid...
Recombination has been shown to be an important force in HIV-1 evolution. contributes increase genetic variation and hinders vaccine design efforts. Several molecular epidemiology studies South America described the circulation of subtypes B, F, C as well several B/F1 recombinants. This study performed by nucleotide sequencing at least two genes 89 samples from Uruguay a complex epidemic characterized cocirculation subtype strains, together with group BF1 recombinant viruses, including...
Long term non-progressor patients (LTNPs) are characterized by the natural control of HIV-1 infection. This is related to host genetic, immunological and virological factors. In this work, phylogenetic analysis proviral nucleotide sequences in env gene from a Spanish LTNPs cohort identified cluster 6 controllers infected with closely-related viruses. The showed common clinical epidemiological features: drug user practices, infection same city (Madrid, Spain) at time (late 70's-early 80's)....
Exosome-derived miR-21 was independently associated with CD4 T cell decline in HIV-1-infected elite controllers (OR 0.369, 95% CI 0.137-0.994, p = 0.049). Also, a negative correlation between expression and MCP-1 level found (r -0.649, 0.020), while no soluble biomarkers or cellular immune activation found.
Within human immunodeficiency virus type 1 (HIV-1)-infected patients, there are those who have been infected for more than 10 years with a CD4 + cell count of >500 cells μl −1 and remain asymptomatic without antiretroviral therapy; these patients designated long-term non-progressors (LTNPs). In set 16 LTNPs, viral dating, DNA load, quasispecies heterogeneity antibody (Ab) titres against gp160 β 2 microglobulin ( m) were determined. Plasma RNA CD8 T-cell numbers estimated in three samples...
The objective of the present study was to determine if natural suppression plasma viremia below detection limit commercial assays (50–80 copies HIV-1 RNA/ml) can contain evolution. quasispecies complexity in PBMC DNA assessed env gene at two time points 14 long-term nonprogressors (LTNPs). Sequence changes consistent with viral evolution found all patients a median RNA load >100 copies/ml. Evidence low-level detected four intermittent and >80 No significant observed three LTNPs persistent...
The understanding of HIV-1 pathogenesis and clinical progression is incomplete due to the variable contribution host, immune, viral factors. involvement factors has been investigated in extreme phenotypes from rapid progressors long-term non-progressors (LTNPs). Among proteins, envelope glycoprotein complex (Env) concentrated on many studies for its important role immune response first steps replication. In this study, we analyzed 41 Envs 24 patients with different rates loads (VLs),...