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1.
AIDS Res Hum Retroviruses ; 17(16): 1481-8, 2001 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-11709092

RESUMEN

c-Myb is expressed in proliferating T cells. Fifteen c-Myb-binding sites can be identified in the HIV-1 long terminal repeat (LTR), suggesting that c-Myb may regulate HIV-1 gene expression and virus replication. Increasing the cellular levels of c-Myb by transient transfection of CEM cells resulted in a 10- to 20-fold activation of HIV-1 LTR-driven gene expression and mutation of one high-affinity Myb-binding site within the LTR reduced this activation by 60 to 70%. Conversely, inhibition of c-Myb expression in MT-2 cells by treatment with c-myb antisense oligonucleotides decreased HIV-1 replication by 85%, as measured by reverse transcriptase activity and cytopathic effects. The effect of c-myb antisense oligonucleotides on HIV-1 gene expression and virus particle production appeared to be independent of cell proliferation, but dependent on the presence of c-Myb activity mediated through the HIV-1 LTR. These data show that c-myb expression affects HIV-1 replication in CD4(+) T cells.


Asunto(s)
Regulación Viral de la Expresión Génica , VIH-1/genética , Proteínas Proto-Oncogénicas c-myb/farmacología , Activación Transcripcional , Replicación Viral/efectos de los fármacos , Linfocitos T CD4-Positivos/virología , Línea Celular , ADN Viral/metabolismo , Duplicado del Terminal Largo de VIH/genética , Duplicado del Terminal Largo de VIH/fisiología , VIH-1/fisiología , Humanos , Proteínas Proto-Oncogénicas c-myb/metabolismo
2.
J Clin Virol ; 22(3): 263-70, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11564591

RESUMEN

BACKGROUND: The Sydney Blood Bank Cohort (SBBC) was infected between 1981 and 1984 with a nef/LTR defective strain of HIV-1. Different responses to HIV-1 infection have emerged between cohort members in the last 5 years. Three recipients (C135, C64 and C49) remain asymptomatic, have normal CD4 T cell counts, below detection (BD) viral loads (VL), remain therapy naive and are termed long-term non-progressors (LTNP). The donor (D36) and the two recipients (C98 and C54) have significantly declining CD4 T cell counts, detectable VL and are now long-term survivors (LTS). In contrast, in the SA cohort, comparison study group for the SBBC, five of 24 remain therapy naïve after 15 years infection with HIV-1 and all have detectable VL. OBJECTIVES: This paper examines different outcomes to long-term infection with HIV-1 in the SBBC and provides a brief overview of the therapy naïve in a comparison study group, the SA cohort. STUDY DESIGN: Retrospective epidemiological follow-up of the SBBC and the SA cohort has been conducted for >15 years. Analysis of CD4 T cell counts, VL and intermittent monitoring of HIV-specific proliferative responses are reviewed. Viral sequence changes in the SBBC will be considered. RESULTS: Prior to therapy D36 had a CD4 T cell count of 160/mm(3) and plasma VL of 9900 copies/ml while C98 had a CD4 T cell count of 387/mm(3) and plasma VL of 11491 copies/ml. After 1 month of therapy, plasma VL was BD (<400 copies/ml) and both showed significant increase in CD4 T cell counts. Molecular changes have occurred in D36 and C98 viral strains, the most recently evolved quasispecies have larger deletions in the nef/LTR region. CONCLUSIONS: Infection with nef/LTR deleted HIV-1 has resulted in slower disease progression for the SBBC. The three LTNP have maintained normal low levels of activated CD8 T cells and strong HIV-specific proliferative responses to HIV-1 p24, which are associated with control of viral replication.


Asunto(s)
Donantes de Sangre , Infecciones por VIH/virología , VIH-1 , Australia/epidemiología , Recuento de Linfocito CD4 , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Eliminación de Gen , Genes nef , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Duplicado del Terminal Largo de VIH , Sobrevivientes de VIH a Largo Plazo/estadística & datos numéricos , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Masculino , Análisis de Regresión , Estudios Retrospectivos , Carga Viral
3.
J Biomed Sci ; 7(2): 128-35, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10754387

RESUMEN

Two Australian HIV-1 isolates, derived from patient blood (HIV(MBC200)) and cerebrospinal fluid (HIV(MBC925)), were characterized after in vitro culture in peripheral blood mononuclear cells (PBMC). Although virus replication was similar, as measured by cell-free reverse transcriptase activity, only one of the two isolates (HIV-1(MCB200)) consistently induced cell syncytia and depleted the PBMC population of CD4+ cells by cell killing. A novel technique, devised for rapidly obtaining high-quality viral sequence data and the full-length genomic sequence of these two isolates, is presented. Analysis of the predicted sequence of the viral Env proteins provides correlates of the observed phenotypes. Phylogenetic analysis derived using near full-length sequence of these and other HIV-1 subtype B genomic sequences (including two other Australian isolates) shows a star-shaped phylogeny with each member having a similar genetic diversity. These data expand the database of genomic sequence available from well-characterized primary clinical isolates of HIV-1 using a novel rapid technique.


Asunto(s)
Genoma Viral , VIH-1/genética , Análisis de Secuencia de ARN/métodos , Síndrome de Inmunodeficiencia Adquirida/virología , Secuencia de Aminoácidos , Antígenos CD4/fisiología , Efecto Citopatogénico Viral , Evolución Molecular , Productos del Gen env/química , VIH-1/aislamiento & purificación , VIH-1/fisiología , Humanos , Datos de Secuencia Molecular , Nueva Gales del Sur , Filogenia , Reacción en Cadena de la Polimerasa , Receptores CXCR4/fisiología , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Victoria , Replicación Viral
4.
J Virol ; 74(3): 1149-57, 2000 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10627525

RESUMEN

An explosive epidemic of human immunodeficiency virus type 1 (HIV-1) has been documented among the injecting drug user population of Kathmandu, Nepal, whose seropositivity rate has risen from 0 to 40% between 1995 and 1997. By using Catrimox to preserve whole-blood RNA at ambient temperature for transportation, HIV-1 envelope V3-V4 sequences were obtained from 36 patients in this group. Analysis of the sequences indicated a homogenous epidemic of subtype C virus, with at least two independent introductions of the virus into the population. Viral diversity was restricted within two transmission subclusters, with the majority of variation occurring in V4. Calculation of the synonymous-to-nonsynonymous mutation ratio (Ks:Ka) across this region showed that significant evolutionary pressure had been experienced during the rapid horizontal spread of the virus in this population, most strongly directed to the region between V3 and V4.


Asunto(s)
Brotes de Enfermedades , Variación Genética , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/genética , Abuso de Sustancias por Vía Intravenosa/complicaciones , Adulto , Secuencia de Aminoácidos , ADN Complementario/genética , Femenino , Genes env , Proteína gp120 de Envoltorio del VIH/genética , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Humanos , Masculino , Datos de Secuencia Molecular , Nepal/epidemiología , Fragmentos de Péptidos/genética , Filogenia , ARN Viral/sangre , Análisis de Secuencia de ADN , Manejo de Especímenes
5.
Nucleic Acids Res ; 28(3): 663-8, 2000 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-10637316

RESUMEN

The human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) represents a model promoter system and the identification and characterisation of cellular proteins that interact with this region has provided a basic understanding about both general eukaryotic and HIV-1 proviral transcriptional regulation. To date a large number of sequence-specific DNA-protein interactions have been described for the HIV-1 LTR. The aim of this report is to provide a comprehensive, updated listing of these HIV-1 LTR interactions. It is intended as a reference point to facilitate on-going studies characterising the identity of cellular proteins interacting with the HIV-1 LTR and the functional role(s) of specific regions of the LTR for HIV-1 replication.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Duplicado del Terminal Largo de VIH/genética , VIH-1/genética , Regiones Promotoras Genéticas/genética , Factores de Transcripción/metabolismo , Elementos de Facilitación Genéticos/genética , Regulación Viral de la Expresión Génica/genética , Humanos , Elementos de Respuesta/genética
6.
N Engl J Med ; 340(22): 1715-22, 1999 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-10352163

RESUMEN

BACKGROUND AND METHODS: The Sydney Blood Bank Cohort consists of a blood donor and eight transfusion recipients who were infected before 1985 with a strain of human immunodeficiency virus type 1 (HIV-1) with a deletion in the region in which the nef gene and the long terminal repeat overlap. Two recipients have died since 1994, at 77 and 83 years of age, of causes unrelated to HIV infection; one other recipient, who had systemic lupus erythematosus, died in 1987 at 22 years of age of causes possibly related to HIV. We present longitudinal immunologic and virologic data on the six surviving members and one deceased member of this cohort through September 30, 1998. RESULTS: The five surviving recipients remain asymptomatic 14 to 18 years after HIV-1 infection without any antiretroviral therapy; however, the donor commenced therapy in February 1999. In three recipients plasma concentrations of HIV-1 RNA are undetectable (<200 copies per milliliter), and in two of these three the CD4 lymphocyte counts have declined by 9 and 30 cells per cubic millimeter per year (P=0.3 and P=0.5, respectively). The donor and two other recipients have median plasma concentrations of HIV-1 RNA of 645 to 2850 copies per milliliter; the concentration has increased in the donor (P<0.001). The CD4 lymphocyte counts in these three cohort members have declined by 16 to 73 cells per cubic millimeter per year (P<0.001). In the recipient who died after 12 years of infection, the median plasma concentration of HIV-1 RNA was 1400 copies per milliliter, with a decline in CD4 lymphocyte counts of 17 cells per cubic millimeter per year (P=0.2). CONCLUSIONS: After prolonged infection with this attenuated strain of HIV-1, there is evidence of immunologic damage in three of the four subjects with detectable plasma HIV-1 RNA. The CD4 lymphocyte counts appear to be stable in the three subjects in whom plasma HIV-1 RNA remains undetectable.


Asunto(s)
Genes nef , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/genética , Adulto , Anciano , Anciano de 80 o más Años , Recuento de Linfocito CD4/efectos de los fármacos , Progresión de la Enfermedad , Femenino , Infecciones por VIH/mortalidad , Duplicado del Terminal Largo de VIH/genética , VIH-1/aislamiento & purificación , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Mutación , ARN Viral/sangre , Carga Viral
9.
AIDS ; 12(6): 555-61, 1998 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-9583594

RESUMEN

OBJECTIVE: To investigate whether members of a transfusion-linked cohort (the Sydney Bloodbank Cohort) infected with a nef-deleted strain of HIV-1 could be differentiated from individuals infected with wild-type strains of HIV-1 by characterizing the Nef antibody response of cohort members. DESIGN: Retrospective and prospective analysis of the nef gene sequence and the antibody response to Nef peptides in HIV-infected subjects. METHODS: Plasma was obtained from all individuals of the Sydney cohort, and from a variety of HIV-1-infected and uninfected controls. Antibodies recognizing full-length recombinant HIV-1NL43 Nef protein and synthetic peptide analogues were assessed by enzyme-linked immunosorbent assay. RESULTS: All 34 individuals infected with wild-type HIV-1 had antibodies reacting with full-length Nef protein as well as with a series of synthetic peptides (6-23-mers) spanning most of the Nef protein of HIV-1NL43. Although the HIV-1 quasispecies infecting the Sydney cohort had a consensus deletion of the nef gene corresponding to amino-acids 165-206, HIV-1 strains from individual members of the cohort had additional deletions comprising up to 80% of the nef gene. Members of the cohort had antibodies to peptides homologous to all regions of the Nef protein tested, except for a single peptide (amino-acids 162-177) that lies within the consensus nef deletion for the cohort quasispecies. CONCLUSION: These data show that nef-deleted strains of HIV-1 can be detected serologically. In the Sydney cohort, detection of antibodies to all regions of Nef tested, except that corresponding to amino-acids 162-177, suggests that observed deletions outside this domain occurred after this virus had infected these subjects and stimulated an immune response. A Nef peptide serological assay may be useful for identifying further examples of individuals infected with nef-deleted, attenuated HIV-1 quasispecies and for assessing the evolution of those variants in vivo.


Asunto(s)
Serodiagnóstico del SIDA/métodos , Genes nef/genética , Anticuerpos Anti-VIH/sangre , VIH-1/inmunología , Eliminación de Secuencia/inmunología , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática/métodos , Mapeo Epitopo , Evolución Molecular , Productos del Gen nef , Seropositividad para VIH/inmunología , Seropositividad para VIH/virología , VIH-1/genética , Humanos , Péptidos/síntesis química , Estudios Prospectivos , Proteínas Recombinantes , Estudios Retrospectivos , Eliminación de Secuencia/genética , Sobrevivientes , Victoria , Productos del Gen nef del Virus de la Inmunodeficiencia Humana
10.
J Virol ; 71(3): 2114-9, 1997 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9032344

RESUMEN

Human immunodeficiency virus type 1 (HIV-1) replicates more efficiently in vitro in differentiated macrophages than in freshly isolated monocytes. We investigated whether this may be partly explained by changes in expression of NF-kappaB with monocyte differentiation. We demonstrated that constitutive expression of NF-kappaB in primary human monocytes changed significantly with differentiation in vitro to monocyte-derived macrophages (MDMs) and differentiation in vivo to alveolar macrophages (AMs). Freshly isolated monocytes constitutively expressed high levels of transcriptionally inactive p50 homodimer which decreased with time in culture in favor of the transcriptionally active p50/p65 and p50/RelB heterodimers. As in MDMs, AMs constitutively expressed p50/p65 and p50/RelB although at lower levels. HIV infection of fresh monocytes failed to induce p50/p65 as seen in MDMs. The replacement of p50 homodimers with transcriptionally active heterodimers following time in culture may partially explain the progressive increase in susceptibility of monocytes to HIV infection during in vitro culture. The change in NF-kappaB components with monocyte differentiation in vivo may also explain the different transcriptional activities of these cell populations in HIV-infected individuals.


Asunto(s)
VIH-1/fisiología , Macrófagos/metabolismo , Monocitos/metabolismo , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas , Factores de Transcripción/metabolismo , Diferenciación Celular , Línea Celular , Humanos , Macrófagos/virología , Monocitos/virología , Subunidad p50 de NF-kappa B , Factor de Transcripción ReIA , Factor de Transcripción ReIB , Replicación Viral
11.
Mol Biol Cell ; 8(2): 313-23, 1997 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9190210

RESUMEN

The gene encoding NFKB1 is autoregulated, responding to NF-kappa B/Rel activation through NF-kappa B binding sites in its promoter, which also contains putative sites for Ets proteins. One of the Ets sites, which we refer to as EBS4, is located next to an NF-kappa B/Rel binding site, kB3, which is absolutely required for activity of the promoter in Jurkat T cells in response to activation by phorbol 12-myristate 13-acetate (PMA), PMA/ionomycin, or the Tax protein from human T cell leukemia virus type I. We show that EBS4 is, required for the full response of the nfkb1 promoter to PMA or PMA/ionomycin in Jurkat cells. EBS4 is bound by Ets-1, Elf-1, and other species. Overexpression of Ets-1 augments the response to PMA/ionomycin and this is reduced by mutation of EBS4. Elf-1 has less effect in conjunction with PMA/ionomycin, but by itself activates the promoter 12-fold. This activation is only partly affected by mutation of EBS4, and a mutant promoter that binds Ets-1, but not Elf-1, at the EBS4 site responds to PMA/ionomycin as efficiently as the wild-type. Ets proteins may be responsible for fine-tuning the activity of the nfkb1 gene in a cell-type-specific manner.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , FN-kappa B/genética , Regiones Promotoras Genéticas , Precursores de Proteínas/genética , Proteínas Proto-Oncogénicas/metabolismo , Factores de Transcripción/metabolismo , Animales , Sitios de Unión , Células COS , Efrina-A2 , Humanos , Ionomicina/farmacología , Células Jurkat , FN-kappa B/metabolismo , Subunidad p50 de NF-kappa B , Proteína Proto-Oncogénica c-ets-1 , Proteínas Proto-Oncogénicas c-ets , Acetato de Tetradecanoilforbol/farmacología , Activación Transcripcional
12.
J Virol ; 70(11): 8010-8, 1996 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8892925

RESUMEN

Sequencing of the reverse transcriptase (RT) region of 26 human immunodeficiency virus type 1 (HIV-1) isolates from eight patients treated with 3'-azido-3'-deoxythymidine (AZT) revealed a mutation at codon 210 from TTG (leucine) to TGG (tryptophan) exclusively in association with resistance to AZT. The mutation Trp-210 was observed in 15 of the 20 isolates phenotypically resistant to AZT, being more commonly observed than resistance-associated mutations at codons 67, 70, and 219. Trp-210 was never observed before the emergence of resistance-associated mutations Leu-41 and Tyr-215, and in a sequential series of five isolates from one patient the order of emergence of mutations was found to be Tyr-215, Leu-41, and then Trp-210. Trp-210 was also found in association with the Leu-41, Asn-67, Arg-70, and Tyr-215 resistance genotype. To define the role of Trp-210 in AZT resistance, molecular HIV-1 clones were constructed with various combinations of RT mutations at codons 41, 67, 70, 210, and 215 and tested for susceptibility to AZT. In clones with polymerase genes derived either from HXB2-D or clinical isolates, Trp-210 alone did not increase AZT resistance, whereas in conjunction with Leu-41 and Tyr-215, Trp-210 contributed to high-level resistance (50% inhibitory concentration of >1 microM). In HXB2-D, Trp-210 with Tyr-215 generated a virus with resistance comparable to one with Leu-41, Tyr-215, and Trp-210. Inserting Trp-210 into the genetic context of mutations at codons 41, 67, 70, and 215 further enhanced resistance from a 50% inhibitory concentration of 1.44 microM to 8.41 microM. Molecular modeling of the tertiary structure of HIV-1 RT revealed that the distance between the side chains of Trp-210 (in helix alphaF) and Tyr-215 (in strand beta11a) approximated 4 A (1 A = 0.1 nm), sufficiently close to result in significant energetic interaction between these two aromatic side chains. In conclusion, Trp-210 contributes significantly to phenotypic AZT resistance of HIV-1 by augmenting resistance at least three- to sixfold in the context of two resistant genotypes, and its effect may require an interaction with an aromatic amino acid at position 215.


Asunto(s)
Infecciones por VIH/virología , Transcriptasa Inversa del VIH/química , VIH-1/enzimología , Leucina , Inhibidores de la Transcriptasa Inversa/farmacología , Triptófano , Zidovudina/farmacología , Secuencia de Bases , Línea Celular , Línea Celular Transformada , ADN Viral , Farmacorresistencia Microbiana , Infecciones por VIH/tratamiento farmacológico , Transcriptasa Inversa del VIH/genética , Transcriptasa Inversa del VIH/metabolismo , VIH-1/efectos de los fármacos , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Modelos Moleculares , Datos de Secuencia Molecular , Mutación Puntual
13.
J Virol ; 70(10): 6665-72, 1996 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8794302

RESUMEN

We report the discovery of a fourth Sp1 binding site at the 5' end of the U3 region of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (HIV-1 Sp1 IV), localized to HXB2 nucleotides -433 to -441. This site is shown to bind Sp1 protein specifically in electrophoretic mobility shift assays. Sp1 protein appears to bind to HIV-1 Spl IV with 5 to 10 times lower affinity than to a consensus Sp1 site. Mutation of HIV-1 Sp1 IV in an HXB2-derived long terminal repeat-chloramphenicol acetyltransferase reporter construct gave no significant change in positive-sense transcription but abolished both basal and phorbol myristate acetate-activated negative-sense transcription. Taken together, the results further define the HIV-1 negative-sense promoter as an Sp1-dependent, phorbol myristate acetate-responsive, and Tat-inhibited promoter initiating at HXB2 nucleotide -450.


Asunto(s)
Duplicado del Terminal Largo de VIH/genética , VIH-1/genética , Transcripción Genética , Elementos sin Sentido (Genética) , Humanos , Mutación , Regiones Promotoras Genéticas , Análisis de Secuencia
15.
Science ; 271(5257): 1791-2, 1996 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-17812357
16.
Science ; 270(5238): 988-91, 1995 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-7481804

RESUMEN

A blood donor infected with human immunodeficiency virus-type 1 (HIV-1) and a cohort of six blood or blood product recipients infected from this donor remain free of HIV-1-related disease with stable and normal CD4 lymphocyte counts 10 to 14 years after infection. HIV-1 sequences from either virus isolates or patient peripheral blood mononuclear cells had similar deletions in the nef gene and in the region of overlap of nef and the U3 region of the long terminal repeat (LTR). Full-length sequencing of one isolate genome and amplification of selected HIV-1 genome regions from other cohort members revealed no other abnormalities of obvious functional significance. These data show that survival after HIV infection can be determined by the HIV genome and support the importance of nef or the U3 region of the LTR in determining the pathogenicity of HIV-1.


Asunto(s)
Donantes de Sangre , Genes nef , Infecciones por VIH/virología , Duplicado del Terminal Largo de VIH , VIH-1/genética , VIH-1/patogenicidad , Adulto , Anciano , Composición de Base , Secuencia de Bases , Transfusión Sanguínea , Recuento de Linfocito CD4 , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Reordenamiento Génico , Genoma Viral , Infecciones por VIH/inmunología , Infecciones por VIH/transmisión , VIH-1/fisiología , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Familia de Multigenes , Eliminación de Secuencia , Virulencia , Replicación Viral
17.
Virology ; 212(1): 58-68, 1995 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-7545854

RESUMEN

Foscarnet is a broad-spectrum viral DNA polymerase inhibitor active in vitro and in vivo against human immunodeficiency virus type 1 (HIV-1). Strains of HIV-1 resistant to foscarnet were selected by in vitro passage in increasing concentrations of drug. Reduced susceptibility to foscarnet was evident at the levels of both HIV-1 replication and reverse transcriptase. Biologically cloned, foscarnet-resistant strains with distinct genotypes were hypersensitive to zidovudine, azidodeoxyuridine, nevirapine, and R82913 but had unchanged susceptibility to zalcitibine and didanosine. The reverse transcriptase of foscarnet-resistant strains had unique substitutions Glu89-Lys, Leu92-Ile, or Ser156-Ala, the third being associated with six polymorphic changes. Introduction of these mutations into wild-type HIV-1 by site-directed mutagenesis confirmed their role in foscarnet resistance. In the three-dimensional structure of the reverse transcriptase enzyme these amino acids are located close to the template strand of the template primer and far away from the putative pyrophosphate binding site, suggesting that the mechanism by which HIV-1 becomes resistant to foscarnet is indirect. Foscarnet resistance is thus likely to be mediated through an altered interaction of the mutant enzyme with the template strand of the template primer which distorts the geometry of the polymerase active site and thereby decreases foscarnet binding.


Asunto(s)
Foscarnet/farmacología , VIH-1/efectos de los fármacos , Secuencia de Aminoácidos , Secuencia de Bases , Cartilla de ADN/química , Farmacorresistencia Microbiana , Genes pol , Transcriptasa Inversa del VIH , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , ADN Polimerasa Dirigida por ARN/genética , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Relación Estructura-Actividad
18.
J Med Virol ; 46(3): 238-43, 1995 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-7561796

RESUMEN

Sequential human immunodeficiency virus type 1 (HIV-1) isolates were obtained over a 29-month period from a person before, during, and after AZT therapy. DNA sequence analysis of polymerase chain-amplified reverse-transcriptase gene showed a gradual accumulation of mutations to peak resistance (IC50 2.13 microM AZT) in association with mutations at codons 44, 210, and 369, as well as at 41, 67, 70, and 215. Eight months after cessation of AZT therapy, when an HIV-1 isolate from the patient was again sensitive to AZT, these mutations had all returned to the pretherapy sequence.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/virología , VIH-1/enzimología , Mutación , ADN Polimerasa Dirigida por ARN/genética , Zidovudina/uso terapéutico , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Células Cultivadas , ADN Viral , Farmacorresistencia Microbiana , Femenino , Estudios de Seguimiento , Genes Virales , Transcriptasa Inversa del VIH , VIH-1/efectos de los fármacos , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular
19.
J Leukoc Biol ; 56(3): 289-93, 1994 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8083601

RESUMEN

Cytocidal retrovirus infection is characterized by rapid accumulation of unintegrated viral DNA forms. These are thought to be generated by multiple rounds of reinfection and have been suggested to play a central role in cytopathogenesis. Here we have reviewed the work done in this area with HIV-1, mostly using acutely and chronically infected T cell and monocytic cell lines and in some cases T cells blocked at S phase of the cell cycle by aphidicolin treatment. To these studies, we have compared our findings with HIV-1 infected primary peripheral blood monocyte-derived macrophages and untreated and growth-arrested MT-2 cells, two biologically disparate cell populations. Using 1- and 2-long terminal repeat (LTR) circular forms as indicators of unintegrated viral DNA, we found similar rapid accumulation in both untreated and growth-arrested MT-2 cells. In contrast, we found much lower levels in monocyte/macrophages. Our findings suggest that accumulation of unintegrated viral DNA does not require virus production and reinfection in growth-arrested T cells. The significantly lower levels found in monocyte/macrophages may reflect superinfection resistance, allowing the maintenance of a persistent infection.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/metabolismo , ADN Viral/metabolismo , VIH-1/genética , VIH-1/aislamiento & purificación , Monocitos/metabolismo , Monocitos/microbiología , Linfocitos T/metabolismo , Linfocitos T/microbiología , Síndrome de Inmunodeficiencia Adquirida/genética , Síndrome de Inmunodeficiencia Adquirida/patología , Secuencia de Bases , ADN Viral/análisis , ADN Viral/genética , Humanos , Datos de Secuencia Molecular , Monocitos/química , Linfocitos T/química
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