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  1 / 282877 MEDLINE  
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[PMID]:25403143
[Au] Autor:Satyanarayan S; Kapur A; Azhar S; Yeldandi V; Schneider JA
[Ad] Dirección:Pritzker School of Medicine, University of Chicago, Chicago, USA.
[Ti] Título:Women Connected to at Risk Indian Men Who Have Sex with Men: An Unexplored Network.
[So] Fuente:AIDS Behav;19(6):1031-6, 2015 Jun.
[Is] ISSN:1573-3254
[Cp] País de publicación:United States
[La] Idioma:eng
[Ab] Resumen:Little is known about the women connected to Indian MSM and their impact on HIV risk. We surveyed 240 Indian MSM, who identified their social networks (n = 7,092). Women (n = 1,321) comprised 16.7 % of the network, with 94.7 % representing non-sexual connections. MSM were classified as having low, moderate, or high female network proportion. MSM with moderate female network proportion (8-24 % total network) had significantly lowered odds of HIV seropositivity (AOR = 0.24, 95 % CI = 0.1-0.6). This suggests moderate proportions of female connections could mediate HIV risk. HIV prevention interventions in India could consider the greater involvement of women among their target audiences. Se sabe poco sobre las mujeres conectadas a HSH en India y su impacto en el riesgo de VIH. Se encuestó a 240 HSH indios, quienes identificaron sus redes sociales (n = 7,092). Las mujeres (n = 1,321) formaron al 16.7 % de la red, del cual el 94.7 % representa conexiones no sexuales. Los HSH se clasificaron como baja, moderada o alta proporción de red femenina. HSH con proporción moderada de red femenina (8-24 % del red total) tuvieron un riesgo significativamente reducido de seropositividad de VIH (AOR = 0,24; IC 95 % = 0,1-0,6). Esto sugiere que tener una proporción moderada de contactos femeninos podría atenuar el riesgo de VIH. Las intervenciones de prevención del VIH en India podrían considerar una mayor participación de las mujeres en su público objetivo.
[Pt] Tipo de publicación:JOURNAL ARTICLE
[Em] Mes de ingreso:1506
[Cu] Fecha actualización por clase:150620
[Lr] Fecha última revisión:150620
[Sb] Subgrupo de revista:IM
[St] Status:In-Data-Review
[do] DOI:10.1007/s10461-014-0946-1


  2 / 282877 MEDLINE  
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[PMID]:25733891
[Au] Autor:Balzarini J; Das K; Bernatchez JA; Martinez SE; Ngure M; Keane S; Ford A; Maguire N; Mullins N; John J; Kim Y; Dehaen W; Vande Voorde J; Liekens S; Naesens L; Götte M; Maguire AR; Arnold E
[Ad] Dirección:Rega Institute for Medical Research and jan.balzarini@rega.kuleuven.be....
[Ti] Título:Alpha-carboxy nucleoside phosphonates as universal nucleoside triphosphate mimics.
[So] Fuente:Proc Natl Acad Sci U S A;112(11):3475-80, 2015 Mar 17.
[Is] ISSN:1091-6490
[Cp] País de publicación:United States
[La] Idioma:eng
[Ab] Resumen:Polymerases have a structurally highly conserved negatively charged amino acid motif that is strictly required for Mg(2+) cation-dependent catalytic incorporation of (d)NTP nucleotides into nucleic acids. Based on these characteristics, a nucleoside monophosphonate scaffold, α-carboxy nucleoside phosphonate (α-CNP), was designed that is recognized by a variety of polymerases. Kinetic, biochemical, and crystallographic studies with HIV-1 reverse transcriptase revealed that α-CNPs mimic the dNTP binding through a carboxylate oxygen, two phosphonate oxygens, and base-pairing with the template. In particular, the carboxyl oxygen of the α-CNP acts as the potential equivalent of the α-phosphate oxygen of dNTPs and two oxygens of the phosphonate group of the α-CNP chelate Mg(2+), mimicking the chelation by the ß- and γ-phosphate oxygens of dNTPs. α-CNPs (i) do not require metabolic activation (phosphorylation), (ii) bind directly to the substrate-binding site, (iii) chelate one of the two active site Mg(2+) ions, and (iv) reversibly inhibit the polymerase catalytic activity without being incorporated into nucleic acids. In addition, α-CNPs were also found to selectively interact with regulatory (i.e., allosteric) Mg(2+)-dNTP-binding sites of nucleos(t)ide-metabolizing enzymes susceptible to metabolic regulation. α-CNPs represent an entirely novel and broad technological platform for the development of specific substrate active- or regulatory-site inhibitors with therapeutic potential.
[Mh] Términos MeSH primario: Nucleósidos/farmacología
Nucleótidos/farmacología
Organofosfonatos/farmacología
[Mh] Términos MeSH secundario: Regulación Alostérica/efectos de drogas
Secuencia de Bases
Biocatálisis/efectos de drogas
Extractos Celulares
ADN Polimerasa Dirigida por ADN/metabolismo
Farmacorresistencia Viral/efectos de drogas
Transcriptasa Inversa del VIH/antagonistas & inhibidores
Transcriptasa Inversa del VIH/química
Transcriptasa Inversa del VIH/metabolismo
Células HeLa
Humanos
Cinética
Modelos Moleculares
Datos de Secuencia Molecular
Mutación/genética
Nucleósidos/química
Nucleótidos/química
Organofosfonatos/química
Inhibidores de Transcriptasa Inversa/química
Inhibidores de Transcriptasa Inversa/farmacología
Estereoisomerismo
[Pt] Tipo de publicación:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nombre de substancia:
0 (Cell Extracts); 0 (Nucleosides); 0 (Nucleotides); 0 (Organophosphonates); 0 (Reverse Transcriptase Inhibitors); EC 2.7.7.- (reverse transcriptase, Human immunodeficiency virus 1); EC 2.7.7.49 (HIV Reverse Transcriptase); EC 2.7.7.7 (DNA-Directed DNA Polymerase)
[Em] Mes de ingreso:1506
[Cu] Fecha actualización por clase:150620
[Lr] Fecha última revisión:150620
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:150318
[St] Status:MEDLINE
[do] DOI:10.1073/pnas.1420233112


  3 / 282877 MEDLINE  
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[PMID]:25522204
[Au] Autor:Vernekar SK; Liu Z; Nagy E; Miller L; Kirby KA; Wilson DJ; Kankanala J; Sarafianos SG; Parniak MA; Wang Z
[Ad] Dirección:Center for Drug Design, Academic Health Center, University of Minnesota , 516 Delaware Street SE, PWB 7-224, MMC 204 Minneapolis, Minnesota 55455, United States.
[Ti] Título:Design, synthesis, biochemical, and antiviral evaluations of C6 benzyl and C6 biarylmethyl substituted 2-hydroxylisoquinoline-1,3-diones: dual inhibition against HIV reverse transcriptase-associated RNase H and polymerase with antiviral activities.
[So] Fuente:J Med Chem;58(2):651-64, 2015 Jan 22.
[Is] ISSN:1520-4804
[Cp] País de publicación:United States
[La] Idioma:eng
[Ab] Resumen:Reverse transcriptase (RT) associated ribonuclease H (RNase H) remains the only virally encoded enzymatic function not targeted by current chemotherapy against human immunodeficiency virus (HIV). Although numerous chemotypes have been reported to inhibit HIV RNase H biochemically, few show significant antiviral activity against HIV. We report herein the design, synthesis, and biological evaluations of a novel variant of 2-hydroxyisoquinoline-1,3-dione (HID) scaffold featuring a crucial C-6 benzyl or biarylmethyl moiety. The synthesis involved a recently reported metal-free direct benzylation between tosylhydrazone and boronic acid, which allowed the generation of structural diversity for the hydrophobic aromatic region. Biochemical studies showed that the C-6 benzyl and biarylmethyl HID analogues, previously unknown chemotypes, consistently inhibited HIV RT-associated RNase H and polymerase with IC50s in low to submicromolar range. The observed dual inhibitory activity remained uncompromised against RT mutants resistant to non-nucleoside RT inhibitors (NNRTIs), suggesting the involvement of binding site(s) other than the NNRTI binding pocket. Intriguingly, these same compounds inhibited the polymerase, but not the RNase H function of Moloney Murine Leukemia Virus (MoMLV) RT and also inhibited Escherichia coli RNase H. Additional biochemical testing revealed a substantially reduced level of inhibition against HIV integrase. Molecular docking corroborates favorable binding of these analogues to the active site of HIV RNase H. Finally, a number of these analogues also demonstrated antiviral activity at low micromolar concentrations.
[Mh] Términos MeSH primario: Antivirales/síntesis química
Transcriptasa Inversa del VIH/antagonistas & inhibidores
Inhibidores de la Sintesis del Ácido Nucleico/síntesis química
Inhibidores de Transcriptasa Inversa/síntesis química
Ribonucleasa H del Virus de la Inmunodeficiencia Humana/antagonistas & inhibidores
[Mh] Términos MeSH secundario: Antivirales/farmacología
Diseño de Drogas
Inhibidores de la Sintesis del Ácido Nucleico/farmacología
Inhibidores de Transcriptasa Inversa/farmacología
Relación Estructura-Actividad
[Pt] Tipo de publicación:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nombre de substancia:
0 (Antiviral Agents); 0 (Nucleic Acid Synthesis Inhibitors); 0 (Reverse Transcriptase Inhibitors); EC 2.7.7.49 (HIV Reverse Transcriptase); EC 3.1.26.4 (Ribonuclease H, Human Immunodeficiency Virus)
[Em] Mes de ingreso:1503
[Cu] Fecha actualización por clase:150620
[Lr] Fecha última revisión:150620
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:150122
[St] Status:MEDLINE
[do] DOI:10.1021/jm501132s


  4 / 282877 MEDLINE  
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[PMID]:25371202
[Au] Autor:Rosemary Bastian A; Nangarlia A; Bailey LD; Holmes A; Kalyana Sundaram RV; Ang C; Moreira DR; Freedman K; Duffy C; Contarino M; Abrams C; Root M; Chaiken I
[Ad] Dirección:From the Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, the School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104....
[Ti] Título:Mechanism of multivalent nanoparticle encounter with HIV-1 for potency enhancement of peptide triazole virus inactivation.
[So] Fuente:J Biol Chem;290(1):529-43, 2015 Jan 2.
[Is] ISSN:1083-351X
[Cp] País de publicación:United States
[La] Idioma:eng
[Ab] Resumen:Entry of HIV-1 into host cells remains a compelling yet elusive target for developing agents to prevent infection. A peptide triazole (PT) class of entry inhibitor has previously been shown to bind to HIV-1 gp120, suppress interactions of the Env protein at host cell receptor binding sites, inhibit cell infection, and cause envelope spike protein breakdown, including gp120 shedding and, for some variants, virus membrane lysis. We found that gold nanoparticle-conjugated forms of peptide triazoles (AuNP-PT) exhibit substantially more potent antiviral effects against HIV-1 than corresponding peptide triazoles alone. Here, we sought to reveal the mechanism of potency enhancement underlying nanoparticle conjugate function. We found that altering the physical properties of the nanoparticle conjugate, by increasing the AuNP diameter and/or the density of PT conjugated on the AuNP surface, enhanced potency of infection inhibition to impressive picomolar levels. Further, compared with unconjugated PT, AuNP-PT was less susceptible to reduction of antiviral potency when the density of PT-competent Env spikes on the virus was reduced by incorporating a peptide-resistant mutant gp120. We conclude that potency enhancement of virolytic activity and corresponding irreversible HIV-1 inactivation of PTs upon AuNP conjugation derives from multivalent contact between the nanoconjugates and metastable Env spikes on the HIV-1 virus. The findings reveal that multispike engagement can exploit the metastability built into virus the envelope to irreversibly inactivate HIV-1 and provide a conceptual platform to design nanoparticle-based antiviral agents for HIV-1 specifically and putatively for metastable enveloped viruses generally.
[Mh] Términos MeSH primario: Fármacos Anti-VIH/farmacología
Proteína gp120 de Envoltorio del VIH/antagonistas & inhibidores
VIH-1/efectos de drogas
Nanoconjugados/toxicidad
Péptidos/farmacología
Triazoles/farmacología
[Mh] Términos MeSH secundario: Fármacos Anti-VIH/síntesis química
Línea Celular Tumoral
Relación Dosis-Respuesta a Droga
Oro/química
Proteína gp120 de Envoltorio del VIH/química
VIH-1/crecimiento & desarrollo
Humanos
Nanoconjugados/ultraestructura
Tamaño de la Partícula
Péptidos/síntesis química
Unión Proteica
Triazoles/síntesis química
Inactivación de Virus/efectos de drogas
Internalización del Virus/efectos de drogas
[Pt] Tipo de publicación:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nombre de substancia:
0 (Anti-HIV Agents); 0 (HIV Envelope Protein gp120); 0 (Nanoconjugates); 0 (Peptides); 0 (Triazoles); 7440-57-5 (Gold)
[Em] Mes de ingreso:1504
[Cu] Fecha actualización por clase:150620
[Lr] Fecha última revisión:150620
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:150105
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M114.608315


  5 / 282877 MEDLINE  
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[PMID]:25437435
[Au] Autor:Johnson GT; Autin L; Al-Alusi M; Goodsell DS; Sanner MF; Olson AJ
[Ad] Dirección:1] Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA. [2] Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA. [3] California Institute for Quantitative ...
[Ti] Título:cellPACK: a virtual mesoscope to model and visualize structural systems biology.
[So] Fuente:Nat Methods;12(1):85-91, 2015 Jan.
[Is] ISSN:1548-7105
[Cp] País de publicación:United States
[La] Idioma:eng
[Ab] Resumen:cellPACK assembles computational models of the biological mesoscale, an intermediate scale (10-100 nm) between molecular and cellular biology scales. cellPACK's modular architecture unites existing and novel packing algorithms to generate, visualize and analyze comprehensive three-dimensional models of complex biological environments that integrate data from multiple experimental systems biology and structural biology sources. cellPACK is available as open-source code, with tools for validation of models and with 'recipes' and models for five biological systems: blood plasma, cytoplasm, synaptic vesicles, HIV and a mycoplasma cell. We have applied cellPACK to model distributions of HIV envelope protein to test several hypotheses for consistency with experimental observations. Biologists, educators and outreach specialists can interact with cellPACK models, develop new recipes and perform packing experiments through scripting and graphical user interfaces at http://cellPACK.org/.
[Mh] Términos MeSH primario: Algoritmos
Modelos Biológicos
Biología de Sistemas
[Mh] Términos MeSH secundario: Biología Computacional/métodos
Simulación por Computador
VIH/ultraestructura
Humanos
Biología Molecular
Programas Informáticos
[Pt] Tipo de publicación:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; VALIDATION STUDIES
[Em] Mes de ingreso:1503
[Cu] Fecha actualización por clase:150620
[Lr] Fecha última revisión:150620
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:141231
[St] Status:MEDLINE
[do] DOI:10.1038/nmeth.3204


  6 / 282877 MEDLINE  
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[PMID]:25033205
[Au] Autor:Dourado I; MacCarthy S; Lima C; Veras MA; Kerr L; de Brito AM; Gruskin S
[Ad] Dirección:a Instituto de Saúde Coletiva/Universidade Federal da Bahia , Salvador , Brazil.
[Ti] Título:What's pregnancy got to do with it? Late presentation to HIV/AIDS services in Northeastern Brazil.
[So] Fuente:AIDS Care;26(12):1514-20, 2014.
[Is] ISSN:1360-0451
[Cp] País de publicación:England
[La] Idioma:eng
[Ab] Resumen:Despite the known benefits of early treatment initiation for individual morbidity and mortality, as well as for reducing the risk of transmission, late presentation (LP) to HIV/AIDS services remains a major concern in many countries. There is little information on LP from middle- and low-income countries and studies that do evaluate LP commonly disaggregate data by sex. It is rare, however, for researchers to further disaggregate the data by pregnancy status so it remains unclear if pregnancy status modifies the effects associated with sex. The study was conducted at the only State Reference Center for HIV/AIDS in Salvador, Brazil's third largest city. LP was defined as a patient accessing services with a CD4 < 350 cells/mm(3). Data were abstracted from the electronic medical records of 1421 patients presenting between 2007 and 2009. CD4 counts and viral load (VL) information was validated with data from the National CD4/VL Database. Descriptive and bivariate statistics were conducted to inform the multivariate analysis. Adjusted prevalence ratios (APR) were estimated using generalized linear models due to the high frequency of the outcome. Half of the sample (52.5%; n = 621) was classified as LP. Compared to the prevalence among pregnant women (21.1%), the prevalence of LP was more than twice as high among non-pregnant women (56.0%) and among men (55.4%). The multivariate analysis demonstrated no statistical difference between men and nonpregnant women (APR 1.04; 95%CI 0.92-1.19), but the APR of LP for nonpregnant women was 53% less than men (APR 0.47; 95%CI 0.33-0.68). These results highlight the importance of analyzing data disaggregated not only by sex but also by pregnancy status to accurately identify the risk factors associated with LP so that programs and policies can effectively and efficiently address LP in Brazil and beyond.
[Mh] Términos MeSH primario: Terapia Antirretroviral Altamente Activa
Recuento de Linfocito CD4
Infecciones por VIH/diagnóstico
Infecciones por VIH/quimioterapia
Complicaciones Infecciosas del Embarazo/diagnóstico
Complicaciones Infecciosas del Embarazo/quimioterapia
[Mh] Términos MeSH secundario: Síndrome de Inmunodeficiencia Adquirida/diagnóstico
Síndrome de Inmunodeficiencia Adquirida/quimioterapia
Adolescente
Adulto
Terapia Antirretroviral Altamente Activa/métodos
Brasil/epidemiología
Estudios Transversales
Diagnóstico Tardío
Progresión de la Enfermedad
Femenino
Infecciones por VIH/sangre
Infecciones por VIH/epidemiología
Humanos
Masculino
Mediana Edad
Embarazo
Complicaciones Infecciosas del Embarazo/sangre
Complicaciones Infecciosas del Embarazo/epidemiología
Resultado del Embarazo
Prevalencia
Factores de Riesgo
Factores de Tiempo
Carga Viral/efectos de drogas
[Pt] Tipo de publicación:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Em] Mes de ingreso:1504
[Cu] Fecha actualización por clase:150620
[Lr] Fecha última revisión:150620
[Sb] Subgrupo de revista:IM; X
[Da] Fecha de ingreso para procesamiento:141007
[St] Status:MEDLINE
[do] DOI:10.1080/09540121.2014.938016


  7 / 282877 MEDLINE  
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[PMID]:25147212
[Au] Autor:Kvaratskhelia M; Sharma A; Larue RC; Serrao E; Engelman A
[Ad] Dirección:Center for Retrovirus Research and College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA alan_engelman@dfci.harvard.edu....
[Ti] Título:Molecular mechanisms of retroviral integration site selection.
[So] Fuente:Nucleic Acids Res;42(16):10209-25, 2014.
[Is] ISSN:1362-4962
[Cp] País de publicación:England
[La] Idioma:eng
[Ab] Resumen:Retroviral replication proceeds through an obligate integrated DNA provirus, making retroviral vectors attractive vehicles for human gene-therapy. Though most of the host cell genome is available for integration, the process of integration site selection is not random. Retroviruses differ in their choice of chromatin-associated features and also prefer particular nucleotide sequences at the point of insertion. Lentiviruses including HIV-1 preferentially integrate within the bodies of active genes, whereas the prototypical gammaretrovirus Moloney murine leukemia virus (MoMLV) favors strong enhancers and active gene promoter regions. Integration is catalyzed by the viral integrase protein, and recent research has demonstrated that HIV-1 and MoMLV targeting preferences are in large part guided by integrase-interacting host factors (LEDGF/p75 for HIV-1 and BET proteins for MoMLV) that tether viral intasomes to chromatin. In each case, the selectivity of epigenetic marks on histones recognized by the protein tether helps to determine the integration distribution. In contrast, nucleotide preferences at integration sites seem to be governed by the ability for the integrase protein to locally bend the DNA duplex for pairwise insertion of the viral DNA ends. We discuss approaches to alter integration site selection that could potentially improve the safety of retroviral vectors in the clinic.
[Mh] Términos MeSH primario: VIH-1/fisiología
Virus de la Leucemia Murina de Moloney/fisiología
Integración Viral
[Mh] Términos MeSH secundario: Terapia Genética
Vectores Genéticos
VIH-1/enzimología
VIH-1/genética
Humanos
Integrasas/química
Integrasas/metabolismo
Péptidos y Proteínas de Señalización Intercelular/química
Péptidos y Proteínas de Señalización Intercelular/metabolismo
Virus de la Leucemia Murina de Moloney/enzimología
Virus de la Leucemia Murina de Moloney/genética
[Pt] Tipo de publicación:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nombre de substancia:
0 (Intercellular Signaling Peptides and Proteins); 0 (lens epithelium-derived growth factor); EC 2.7.7.- (Integrases)
[Em] Mes de ingreso:1501
[Cu] Fecha actualización por clase:150620
[Lr] Fecha última revisión:150620
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:140917
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gku769


  8 / 282877 MEDLINE  
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[PMID]:25167059
[Au] Autor:Klatt NR; Bosinger SE; Peck M; Richert-Spuhler LE; Heigele A; Gile JP; Patel N; Taaffe J; Julg B; Camerini D; Torti C; Martin JN; Deeks SG; Sinclair E; Hecht FM; Lederman MM; Paiardini M; Kirchhoff F; Brenchley JM; Hunt PW; Silvestri G
[Ad] Dirección:Department of Pharmaceutics, Washington National Primate Research Center, University of Washington, Seattle, Washington, United States of America; Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, United Sta...
[Ti] Título:Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals.
[So] Fuente:PLoS Pathog;10(8):e1004345, 2014 Aug.
[Is] ISSN:1553-7374
[Cp] País de publicación:United States
[La] Idioma:eng
[Ab] Resumen:A rare subset of HIV-infected individuals, designated viremic non-progressors (VNP), remain asymptomatic and maintain normal levels of CD4+ T-cells despite persistently high viremia. To identify mechanisms potentially responsible for the VNP phenotype, we compared VNPs (average >9 years of HIV infection) to HIV-infected individuals who have similar CD4+ T-cell counts and viral load, but who are likely to progress if left untreated ("putative progressors", PP), thus avoiding the confounding effect of differences related to substantial CD4+ T cell depletion. We found that VNPs, compared to PPs, had preserved levels of CD4+ stem cell memory cells (TSCM (p<0.0001), which was associated with decreased HIV infection of these cells in VNPs (r = -0.649, p = 0.019). In addition, VNPs had decreased HIV infection in CD4+ central memory (TCM) cells (p = 0.035), and the total number of TCM cells was associated with increased proliferation of memory CD4+ T cells (r = 0.733, p = 0.01). Our results suggest that, in HIV-infected VNPs, decreased infection of CD4+ TCM and TSCM, cells are involved in preservation of CD4+ T cell homeostasis and lack of disease progression despite high viremia.
[Mh] Términos MeSH primario: Linfocitos T CD4-Positivos/inmunología
Infecciones por VIH/inmunología
Memoria Inmunológica/inmunología
Subgrupos de Linfocitos T/inmunología
Viremia/inmunología
[Mh] Términos MeSH secundario: Linfocitos T CD4-Positivos/virología
Separación Celular
ADN Viral/análisis
Progresión de la Enfermedad
Infecciones por VIH/virología
Humanos
Inmunofenotipificación
Análisis de Secuencia por Matrices de Oligonucleótidos
Células Madre/inmunología
Células Madre/virología
Subgrupos de Linfocitos T/virología
Carga Viral
Viremia/virología
[Pt] Tipo de publicación:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nombre de substancia:
0 (DNA, Viral)
[Em] Mes de ingreso:1506
[Cu] Fecha actualización por clase:150620
[Lr] Fecha última revisión:150620
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:140829
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1004345


  9 / 282877 MEDLINE  
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[PMID]:24760888
[Au] Autor:Abram ME; Ferris AL; Das K; Quinoñes O; Shao W; Tuske S; Alvord WG; Arnold E; Hughes SH
[Ad] Dirección:HIV Drug Resistance Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, USA....
[Ti] Título:Mutations in HIV-1 reverse transcriptase affect the errors made in a single cycle of viral replication.
[So] Fuente:J Virol;88(13):7589-601, 2014 Jul.
[Is] ISSN:1098-5514
[Cp] País de publicación:United States
[La] Idioma:eng
[Ab] Resumen:UNLABELLED: The genetic variation in HIV-1 in patients is due to the high rate of viral replication, the high viral load, and the errors made during viral replication. Some of the mutations in reverse transcriptase (RT) that alter the deoxynucleoside triphosphate (dNTP)-binding pocket, including those that confer resistance to nucleoside/nucleotide analogs, affect dNTP selection during replication. The effects of mutations in RT on the spectrum (nature, position, and frequency) of errors made in vivo are poorly understood. We previously determined the mutation rate and the frequency of different types of mutations and identified hot spots for mutations in a lacZα (the α complementing region of lacZ) reporter gene carried by an HIV-1 vector that replicates using wild-type RT. We show here that four mutations (Y115F, M184V, M184I, and Q151M) in the dNTP-binding pocket of RT that had relatively small effects on the overall HIV-1 mutation rate (less than 3-fold compared to the wild type) significantly increased mutations at some specific positions in the lacZα reporter gene. We also show that changes in a sequence that flanks the reporter gene can affect the mutations that arise in the reporter. These data show that changes either in HIV-1 RT or in the sequence of the nucleic acid template can affect the spectrum of mutations made during viral replication. This could, by implication, affect the generation of drug-resistant mutants and immunological-escape mutants in patients. IMPORTANCE: RT is the viral enzyme that converts the RNA genome of HIV into DNA. Errors made during replication allow the virus to escape from the host's immune system and to develop resistance to the available anti-HIV drugs. We show that four different mutations in RT which are known to be associated with resistance to anti-RT drugs modestly increased the overall frequency of errors made during viral replication. However, the increased errors were not uniformly distributed; the additional errors occurred at a small number of positions (hot spots). Moreover, some of the RT mutations preferentially affected the nature of the errors that were made (some RT mutations caused an increase in insertion and deletion errors; others caused an increase in substitution errors). We also show that sequence changes in a region adjacent to a target gene can affect the errors made within the target gene.
[Mh] Términos MeSH primario: Farmacorresistencia Viral/genética
Infecciones por VIH/virología
Transcriptasa Inversa del VIH/genética
VIH-1/fisiología
Operón Lac/genética
Mutación/genética
Replicación Viral/genética
[Mh] Términos MeSH secundario: Células Cultivadas
ADN Viral/genética
Infecciones por VIH/quimioterapia
Infecciones por VIH/genética
Transcriptasa Inversa del VIH/antagonistas & inhibidores
Humanos
Inhibidores de Transcriptasa Inversa/farmacología
[Pt] Tipo de publicación:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., INTRAMURAL
[Nm] Nombre de substancia:
0 (DNA, Viral); 0 (Reverse Transcriptase Inhibitors); EC 2.7.7.49 (HIV Reverse Transcriptase)
[Em] Mes de ingreso:1501
[Cu] Fecha actualización por clase:150620
[Lr] Fecha última revisión:150620
[Sb] Subgrupo de revista:IM
[Da] Fecha de ingreso para procesamiento:140729
[St] Status:MEDLINE
[do] DOI:10.1128/JVI.00302-14


  10 / 282877 MEDLINE  
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[PMID]:24451161
[Au] Autor:Tucker JD; Rennie S; Social and Ethical Working Group on HIV Cure
[Ad] Dirección:aInstitute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA bUNC Project-China, Guangzhou, China cCenter for Bioethics, Department of Social Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
[Ti] Título:Social and ethical implications of HIV cure research.
[So] Fuente:AIDS;28(9):1247-50, 2014 Jun 1.
[Is] ISSN:1473-5571
[Cp] País de publicación:England
[La] Idioma:eng
[Mh] Términos MeSH primario: Investigación Biomédica/tendencias
Erradicación de la Enfermedad/métodos
Erradicación de la Enfermedad/organización & administración
Infecciones por VIH/quimioterapia
Infecciones por VIH/prevención & control
Comunicación en Salud/ética
Política de Salud
[Mh] Términos MeSH secundario: Infecciones por VIH/psicología
Humanos
[Pt] Tipo de publicación:EDITORIAL; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Em] Mes de ingreso:1501
[Cu] Fecha actualización por clase:150620
[Lr] Fecha última revisión:150620
[Sb] Subgrupo de revista:IM; X
[Da] Fecha de ingreso para procesamiento:140625
[St] Status:MEDLINE
[do] DOI:10.1097/QAD.0000000000000210



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