RESUMO
The nucleotide sequences of the six regions within the normal human cellular locus (c-sis) that correspond to the entire transforming region of the simian sarcoma virus (SSV) genome (v-sis) were determined. The regions are bounded by acceptor and donor splice sites and, except for region 6, resemble exons. Region 6 lacks a 3' donor splice site and terminates -5 base pairs from the 3' v-sis-helper-viral junction. This is consistent with a model proposing that SSV was generated by recombination between proviral DNA of a simian sarcoma associated virus and proto-sis and that introns were spliced out subsequently from a fused viral-sis messenger RNA. This also suggests that the 3' recombination occurred within an exon of the woolly monkey (Lagothrix) genome. The open reading frames predicting the v-sis and c-sis gene products coincide with the stop codon of c-sis located 123 nucleotides into the fifth region of homology. The overall nucleotide homology was 91 percent with substitutions mainly in the third codon positions within the open reading frame and with greatest divergence within the untranslated 3' portion of the sequences. The predicted protein products for v-sis and c-sis are 93 percent homologous. The predicted c-sis gene product is identical in 31 of 31 amino acids to one of the published sequences of platelet-derived growth factor. Thus, c-sis encodes one chain of human platelet-derived growth factor.
Assuntos
Genes Virais , Oncogenes , Fator de Crescimento Derivado de Plaquetas/genética , Retroviridae/genética , Vírus do Sarcoma do Macaco-Barrigudo/genética , Sequência de Aminoácidos , Sequência de Bases , Transformação Celular Neoplásica , Transformação Celular Viral , Códon , Humanos , Proto-Oncogene Mas , Splicing de RNA , RNA Mensageiro/genética , Recombinação Genética , Proteínas Virais/genéticaRESUMO
The Fos protein complex and several Fos-related antigens bind directly or indirectly to a common sequence element that is similar to the consensus binding site for HeLa cell activator protein 1 (AP-1). This element is present in a negative regulatory sequence in the differentiation-sensitive adipocyte gene, aP2; in a transcriptional enhancer for the Gibbon ape leukemia virus; and in a region of the human immunodeficiency virus (HIV) long terminal repeat partially characterized as a negative regulatory element. The protein level and binding activity of Fos and Fos-related antigens increase rapidly after calcium ionophore treatment of a CD4+ human lymphoblast cell line, H9. These data suggest that several proteins may associate with the AP-1 binding site. Moreover, temporally regulated control of the level of each protein could represent a mechanism for modulation of these putative mediators of gene expression.
Assuntos
Proteínas Proto-Oncogênicas/metabolismo , Sequência de Bases , Sítios de Ligação , Calcimicina/farmacologia , Linhagem Celular , Precipitação Química , DNA , Eletroforese em Gel de Poliacrilamida , Elementos Facilitadores Genéticos , HIV/genética , Humanos , Imunoensaio , Técnicas de Imunoadsorção , Dados de Sequência Molecular , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/imunologia , Proteínas Proto-Oncogênicas c-fos , Proto-Oncogenes , Sequências Reguladoras de Ácido Nucleico , Sequências Repetitivas de Ácido Nucleico , Linfócitos T Auxiliares-Indutores/citologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacosRESUMO
Human T-lymphotropic virus type III (HTLV-III) encodes a trans-acting factor that activates the expression of genes linked to the HTLV-III long terminal repeat. By functional mapping of complementary DNA transcripts of viral messenger RNA's the major functional domain of the gene encoding this factor was localized to a region immediately before the env gene of the virus, a region previously thought to be noncoding. This newly identified gene consists of three exons, and its transcription into messenger RNA involves two splicing events bringing together sequences from the 5' part (287 base pairs), middle (268 base pairs), and 3'part (1258 base pairs) of the HTLV-III genome. A similar messenger RNA with a truncated second exon (70 base pairs) does not encode a trans-acting function. It is proposed that this second messenger RNA is the transcript of a gene (3'-orf) located after the env gene. Messenger RNA's were also identified for the env and gag-pol genes of HTLV-III.
Assuntos
Deltaretrovirus/genética , Genes Virais , Fatores de Transcrição/genética , Sequência de Aminoácidos , Sequência de Bases , Mapeamento Cromossômico , Regulação da Expressão Gênica , Genes Reguladores , Humanos , Splicing de RNA , RNA Mensageiro/genética , RNA Viral/genética , Sequências Repetitivas de Ácido Nucleico , Proteínas Virais/genéticaRESUMO
The human B-lymphotropic virus (HBLV) has a double-stranded DNA genome of greater than 110 kilobase pairs, which is consistent with its morphological classification as a herpesvirus. A 9000-base pair cloned probe of HBLV detected specific sequences in DNA and RNA of infected cells but did not hybridize to the genomic DNA of other human herpesviruses including the Epstein-Barr virus, human cytomegalovirus, herpes simplex type I, and varicella-zoster virus. Conversely, while probes obtained from each of the known human herpesvirus readily detected the homologous viral DNA, they did not hybridize to genomic HBLV DNA. This evidence, in addition to serological and morphological distinctions and the biological effects of this virus demonstrate that HBLV is a novel human herpesvirus.
Assuntos
Herpesviridae/genética , Citomegalovirus/genética , DNA Viral/genética , Herpesvirus Saimiriíneo 2/genética , Herpesvirus Humano 3/genética , Herpesvirus Humano 4/genética , Humanos , Hibridização de Ácido Nucleico , Simplexvirus/genéticaRESUMO
To investigate the mechanism by which immune activation augments replication of the human immunodeficiency virus type 1 (HIV-1) in infected T cells, four different classes of T cell mitogens were evaluated for their effects on the HIV-1 long terminal repeat (LTR). Phytohemagglutinin (PHA), a mitogenic lectin; phorbol 12-myristic 13-acetate, a tumor promoter; ionomycin, a calcium ionophore; and tat-1, the trans-activator protein from the human T cell leukemia/lymphoma virus type I (HTLV-I) each stimulated the HIV-1 LTR. Studies of deleted forms of the LTR supported a central role in these responses for the HIV-1 enhancer, which alone was sufficient for mitogen inducibility, but also suggested that other 5' positive and negative regulatory elements contribute to the overall magnitude of the response. Synergistic activation of the HIV-1 LTR (up to several thousandfold) was observed with combinations of these mitogens and the HIV-1--derived tat-III protein. Cyclosporin A, an immunosuppressive agent, inhibited PHA-mediated activation of the HIV-1 LTR but was without effect in the presence of other mitogens. Thus, HIV-1 gene expression and replication appear to be regulated, via the HIV-1 LTR, by the same mitogenic signals that induce T cell activation.
Assuntos
Deltaretrovirus/fisiologia , HIV/crescimento & desenvolvimento , Mitógenos/farmacologia , Proteínas dos Retroviridae/fisiologia , Linfócitos T/imunologia , Fatores de Transcrição/fisiologia , Ativação Viral , Linhagem Celular , Ciclosporinas/farmacologia , Genes Virais , HIV/efeitos dos fármacos , HIV/genética , Transativadores , Transcrição Gênica , Ativação Viral/efeitos dos fármacosRESUMO
The nucleotide sequence of the long terminal repeat sequence (LTR) of the human T-cell leukemia (lymphotropic) virus type III (HTLV-III) was determined. This virus is associated etiologically with the acquired immune deficiency syndrome. The LTR was found to be 634 base pairs in length with U3, R, and U5 regions of 453, 98, and 83 bp, respectively. The proviral DNA is flanked by a 7-base-pair direct repeat. The promoter and polyadenylation signals are situated 27 and 24 base pairs upstream from the respective transcriptional initiation and polyadenylation sites. The primer binding site is complementary to transfer RNA-lysine. The LTR of HTLV-III, like that of HTLV-I, showed a limited homology to enhancer-like sequences within two genes expressed specifically in T lymphocytes, T-cell growth factor, and gamma-interferon. Structural comparisons revealed that the LTR of HTLV-III is distantly related to those of HTLV-I, HTLV-II, and bovine leukemia virus.
Assuntos
Deltaretrovirus/genética , Genes Virais , Sequências Repetitivas de Ácido Nucleico , Evolução Biológica , DNA , DNA Viral , Humanos , Interferon gama/genética , Interleucina-2/genética , Vírus da Leucemia Bovina/genética , Óperon , RNA Viral , Retroviridae/genética , Transcrição GênicaRESUMO
The nucleotide sequence of a transforming human c-sis complementary DNA shows an open reading frame 723 base pairs in length located downstream from an in-phase terminator thymine-guanine-adenine codon. Sequences within this region were identical to those previously determined for the exons of the normal human c-sis gene. Thus, the predicted transforming product, a protein of 27,281 daltons, may be the actual precursor for normal human platelet-derived growth factor chain A.
Assuntos
Transformação Celular Neoplásica/metabolismo , Oncogenes , Fator de Crescimento Derivado de Plaquetas/genética , Animais , Sequência de Bases , Cebidae , Códon , DNA de Neoplasias/genética , Humanos , Hibridização de Ácido NucleicoRESUMO
The 5' nucleotide sequences of the transforming gene of simian sarcoma virus (v-sis) and its human cellular homolog (c-sis) were compared. A short homology was found between helper virus and cellular DNA sequences at the junction of v-sis and c-sis, which may have had a role in the original recombination event leading to the generation of simian sarcoma virus.
Assuntos
Genes Virais , Oncogenes , Retroviridae/genética , Vírus do Sarcoma do Macaco-Barrigudo/genética , Sequência de Bases , Vírus Auxiliares/genética , Humanos , Recombinação GenéticaRESUMO
A novel human B-lymphotropic virus (HBLV) was isolated from the peripheral blood leukocytes of six individuals: two HTLV-III seropositive patients from the United States (one with AIDS-related lymphoma and one with dermatopathic lymphadenopathy), three HTLV-III seronegative patients from the United States (one with angioimmunoblastic lymphadenopathy, one with cutaneous T-cell lymphoma, and one with immunoblastic lymphoma), and one HTLV-III seronegative patient with acute lymphocytic leukemia from Jamaica. All six isolates were closely related by antigenic analysis, and sera from all six virus-positive patients reacted immunologically with each virus isolate. In contrast, only four sera from 220 randomly selected healthy donors and none from 12 AIDS patients without associated lymphoma were seropositive. The virus selectively infected freshly isolated human B cells and converted them into large, refractile mono- or binucleated cells with nuclear and cytoplasmic inclusion bodies. HBLV is morphologically similar to viruses of the herpesvirus family but is readily distinguishable from the known human and nonhuman primate herpesviruses by host range, in vitro biological effects, and antigenic features.
Assuntos
Infecções por Herpesviridae/microbiologia , Herpesviridae/isolamento & purificação , Transtornos Linfoproliferativos/microbiologia , Animais , Linfócitos B/microbiologia , Linhagem Celular , Infecções por Deltaretrovirus/microbiologia , Imunofluorescência , Haplorrinos , Humanos , Microscopia Eletrônica , Linfócitos T/microbiologiaRESUMO
The processes responsible for the multidrug-resistant (Mdr) phenotype in Adriamycin (doxorubicin)-resistant HL-60 leukemia cells (HL-60/AR) are not defined. Since enhanced transcription of resistance-related proteins is associated with Mdr cells, we sought to determine whether changes in the expression of specific transcription factors were a feature characteristic of the Mdr process. Nuclear extracts were prepared from wild-type and resistant cells and compared for their ability to bind DNA consensus sequences for the transcription factors Sp1 and NF kappa B contained in the 5' long terminal repeat region of human immunodeficiency virus type 1. Southwestern (DNA-protein) blots showed a family of DNA-binding proteins of 105 kilodaltons (kDa) that were present only in HL-60/AR cells. Competitive gel shift assays indicated that these factors were related to transcription factor Sp1, and immunoblotting with an Sp1 antibody identified this factor as Sp1. DNase footprinting of the promoter region in the human immunodeficiency virus type 1 5' long terminal repeat showed that protection occurred at two Sp1 sites as well as two NF kappa B sites and the trans-acting region with nuclear extracts only from resistant cells. Preliminary evidence also suggests that phosphorylation may play a negative regulatory role in the activity of Sp1, since calf intestine alkaline phosphatase stimulated the DNA-binding activity of Sp1 in vitro. These results indicate that HL-60/AR cells contain an abundance of DNA-binding proteins, particularly Sp1, which probably interact with other cis-acting regulatory proteins in a cooperative manner.
Assuntos
Proteínas de Ligação a DNA/fisiologia , Resistência a Medicamentos , Fatores de Transcrição/fisiologia , Sequência de Bases , Sítios de Ligação , Western Blotting , Proteínas de Ligação a DNA/metabolismo , Doxorrubicina/farmacologia , Humanos , Leucemia Mieloide , Dados de Sequência Molecular , Sondas de Oligonucleotídeos , Fator de Transcrição Sp1 , Acetato de Tetradecanoilforbol/farmacologia , Fatores de Transcrição/metabolismo , Células Tumorais CultivadasRESUMO
A survey for HBLV (human B-lymphotropic herpesvirus or human herpesvirus 6) sequences by Southern blot analyses was performed on DNA obtained from a variety of pathologically defined tissues, including a number of lymphomas, leukemias, and tissues from other hematologic disorders. Of the over 50 specimens studied, viral sequences were detected in three lymphomas of B cell derivation: an Epstein-Barr virus-positive African Burkitt's lymphoma, a follicular large cell lymphoma (nodular histocytic lymphoma), and two Epstein-Barr virus-negative tumors from a patient with Sjogren's syndrome. These results are the first indication of HBLV sequences associated with B cell tumors in a limited number of cases and raise the possibility that the virus might be involved in the genesis of some B cell tumors.
Assuntos
Linfócitos B/análise , DNA Viral/isolamento & purificação , Herpesviridae/genética , Linfoma/análise , Idoso , Linfócitos B/microbiologia , Linfoma de Burkitt/análise , Linfoma de Burkitt/microbiologia , Pré-Escolar , Feminino , Humanos , Linfoma/microbiologia , Masculino , Pessoa de Meia-Idade , Hibridização de Ácido NucleicoRESUMO
Continuous delivery of therapeutic peptide to the systemic circulation would be the optimal treatment for a variety of diseases. The Baxter TheraCyte system is a membrane encapsulation system developed for implantation of tissues, cells such as endocrine cells or cell lines genetically engineered for therapeutic peptide delivery in vivo. To demonstrate the utility of this system, cell lines were developed which expressed human growth hormone (hGH) at levels exceeding 1 microgram per million cells per day. These were loaded into devices which were then implanted into juvenile nude rats. Significant levels of hGH of up to 2.5 ng/ml were detected in plasma throughout the six month duration of the study. In contrast, animals implanted with free cells showed peak plasma levels of 0.5 to 1.2 ng four days after implantation with no detectable hGH beyond 10 days. Histological examination of explanted devices showed they were vascularized and contained cells that were viable and morphologically healthy. After removal of the implants, no hGH could be detected which confirmed that the source of hGH was from cells contained within the device. The long term expression of human growth hormone as a model peptide has implications for the peptide therapies for a variety of human diseases using membrane encapsulated cells.
Assuntos
Fibroblastos/metabolismo , Fibroblastos/transplante , Terapia Genética/métodos , Hormônio do Crescimento Humano/biossíntese , Hormônio do Crescimento Humano/genética , Animais , Linhagem Celular , Transplante de Células , Engenharia Genética , Hormônio do Crescimento Humano/sangue , Humanos , Membranas Artificiais , RatosRESUMO
Molecular clones of the baboon endogenous viruses 455K, from Papio anubis, and M7, from Papio cynocephalus, have been constructed from unintegrated viral DNA. Although two specific restriction sites do distinguish the two, detailed restriction maps are nearly identical and heteroduplex molecules show complete homology. The latter observations indicate that this endogenous retrovirus genome has been strongly conserved among different species of baboon.
Assuntos
Clonagem Molecular , DNA Viral/genética , Retroviridae/genética , Animais , Sequência de Bases , Enzimas de Restrição do DNA , PapioRESUMO
To achieve efficient delivery and sustained expression of the human factor VIII cDNA in vivo, a minimal-adenoviral (mini-Ad) vector system was developed. The system is composed of a mini-Ad vector with essential cis-elements (less than 1 kb) of the viral genome, an E1-deleted ancillary Ad with packaging attenuation, and an E1-complementing production cell line. Based on this system, MiniAdFVIII was generated to deliver a 27 kb expression cassette consisting of a full-length human factor VIII cDNA flanked by human albumin promoter and genomic sequences. The MiniAdFVIII vector mediated expression of functional human factor VIII in HepG2 and 293 cells. A single-dose intravenous injection of 10(11) viral particles in hemophilic mice of MiniAdFVIII produced a sustained high-level expression of human factor VIII (at 100-800 ng/ml up to 369 days) which corrected the FVIII-deficient phenotype. Safety studies of MiniAdFVIII showed that there were no significant toxic effects in mice and dogs after single intravessel doses of up to 3 x 10(11) and 6 x 10(12) viral particles, respectively. Studies for developing the MiniAdFVIII vector with a site-specific integration mechanism and progress in the development of a human factor VIII-tolerized mouse model for pre-clinical studies of MiniAdFVIII are reported. Further pre-clinical studies and product development of MiniAdFVIII for clinical trials are also discussed.
Assuntos
Adenoviridae/genética , Fator VIII/genética , Técnicas de Transferência de Genes , Terapia Genética , Vetores Genéticos , Hemofilia A/terapia , Animais , Modelos Animais de Doenças , Cães , Humanos , CamundongosRESUMO
The regulation of trans-activating activities of two human hepatocellular carcinoma cell (HCC) lines, HEP-G2 and SK-HEP-1, was investigated. These cells were transfected with the wild-type and a nested series of its 5'-deletion mutants of the long terminal (LTR) repeat derived from HIV-1, which were ligated with the chloramphenicol acetyl transferase gene. These two HCC cell lines exhibited different biological characteristics, reflecting their status of differentiation. Both cell lines showed moderate degrees of constitutive (basal) trans-activating activities. While HEP-G2 cells, which are well differentiated, showed marked degrees of enhancement of trans-activation after treatment with 12-O-tetradecanoylphorbol-13-acetate, SK-HEP-1 cells, which are poorly differentiated, showed only moderate or low degrees of enhancement. These two cell lines up-regulated their trans-activating activities in response to the deletion of some regions of positive and negative regulatory elements, suggesting that they produce trans-acting factors that are quantitatively different from each other, and often employ different sets of positive and negative regulatory elements for trans-activation.
Assuntos
Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Repetição Terminal Longa de HIV/genética , Neoplasias Hepáticas/genética , Sequências Reguladoras de Ácido Nucleico/genética , Ativação Transcricional , Sequência de Bases , Carcinoma Hepatocelular/microbiologia , Diferenciação Celular , Cloranfenicol O-Acetiltransferase/genética , Cloranfenicol O-Acetiltransferase/metabolismo , Ampliador HIV/genética , HIV-1/genética , Humanos , Neoplasias Hepáticas/microbiologia , Dados de Sequência Molecular , NF-kappa B/metabolismo , Plasmídeos , Regiões Promotoras Genéticas/genética , Proteínas Repressoras/metabolismo , Fator de Transcrição Sp1/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Transativadores/metabolismo , Transfecção , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/microbiologia , Células Tumorais Cultivadas/ultraestrutura , Regulação para CimaRESUMO
Trans-activating activities of certain cellular promoter/enhancer genes may reflect the underlying mechanism for cellular differentiation. We have used two promonocytic leukemia cell lines, U937 and HL-CZ, which differ in their differentiation antigen expression. While both cell lines express CD15 antigen, only the former expresses both CD4 and CD10 antigens. These phenotypes suggest that these two cell lines appear to be arrested at different stages of differentiation. Some regions of the long terminal repeat (LTR) of human immunodeficiency virus-1 (HIV-1) contain nucleotide sequences which bind cellular trans-activating factors such as NF-kappa B and Sp1. These sequences are also present in cellular regulatory gene sequences. The cell lines have been transfected by electroporation with a nested series of deletion mutants containing different lengths of the promoter/enhancer region for HIV-LTR. The promoter/enhancer region has been linked to a 'reporter' chloramphenicol acetyl transferase (CAT) gene. We have found that promoter/enhancer trans-activation is markedly enhanced by treating transfected cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), while similar treatment with tumor necrosis factor-alpha (TNF alpha) slightly enhanced activation. U937 cells always showed much greater transactivating activities than did HL-CZ cells. Deletion of a negative regulatory element (NRE) from the LTR resulted in an enhanced transactivation, while deletions affecting NF-kappa B and/or Sp1 binding sites markedly reduced transactivation. Deletion of both NRE and NRF, a second negative regulatory factor binding site, from the LTR restored the transactivation. However, in the presence of TPA, deletion of NRE sequence without concomitant deletion of the downstream NRF binding sequence was sufficient for recovering transactivation. Since these two cell lines have shown subtle differences in these responses, it may be speculated that monocytes at different stages of differentiation may respond in different ways, qualitatively and/or quantitatively, to signal transduction factors involved in the transactivation of cellular genes.
Assuntos
Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide/genética , Ativação Transcricional/genética , Antígenos de Diferenciação/análise , Sequência de Bases , Análise Mutacional de DNA , DNA de Neoplasias/análise , Repetição Terminal Longa de HIV/genética , Humanos , Leucemia Mieloide/imunologia , Dados de Sequência Molecular , Plasmídeos , Acetato de Tetradecanoilforbol/farmacologia , Ativação Transcricional/efeitos dos fármacos , Transfecção , Células Tumorais Cultivadas/imunologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
As a further step in the continuing process of defining the extent and nature of variability of the envelope (env) gene of HIV-1, we have cloned a new Zairian isolate, JY1, and sequenced the env gene of this isolate. Although the restriction map of the env region of JY1 was found to be more similar to that of the American prototype, BH10, than maps of all previously reported Zairian isolates and some American isolates, nucleotide sequencing of the JY1 env gene showed that it is among the most divergent from BH10 yet reported and that it differs from previously reported Zairian isolates almost to the same extent that it differs from BH10. A typical pattern of variable and constant regions was seen. A number of complex duplications were found in the hypervariable regions of JY1. The unique and highly divergent nature of the env gene of JY1 enhances its usefulness as part of a panel of HIV-1 isolates being evaluated in biologic and immunologic studies toward vaccine development.
Assuntos
Genes Virais , HIV/genética , Proteínas do Envelope Viral/genética , Sequência de Aminoácidos , Sequência de Bases , República Democrática do Congo , Glicoproteínas/genética , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência MolecularRESUMO
The long terminal repeats (LTRs) of the human immunodeficiency virus (HIV) the Rous sarcoma virus (RSV) and the copia Drosophila retrotransposon were compared in their capacity to direct expression of the bacterial cat (chloramphenicol acetyltransferase) gene in human, murine, and Drosophila cell lines. The results indicate that HIV and RSV LTR expression is post transcriptionally repressed in the Drosophila cells while copia LTR expression is post-transcriptionally repressed in the human and murine cells.
Assuntos
Drosophila/genética , Genes Reguladores , HIV-1/genética , Processamento Pós-Transcricional do RNA , Regiões Terminadoras Genéticas , Animais , Vírus do Sarcoma Aviário/genética , Linhagem Celular , Cloranfenicol O-Acetiltransferase/genética , Elementos de DNA Transponíveis , Repressão Enzimática , Humanos , CamundongosRESUMO
We have previously described the cloning and sequencing of a novel stain of human immunodeficiency virus type 2 (HIV-2) called HIV-2NIH-Z. A plasmid clone, pHIV2Z, containing the full-length provirus has now been constructed, and virus particles have been obtained upon transfection into COS-1 and H-9 cells. These particles can infect a number of T-cell lines and exert a cytopathic effect on fresh human and macaque peripheral blood lymphocytes. The cloned virus is biologically and morphologically indistinguishable from its parental uncloned strain as shown by restriction enzyme analysis, electron microscopy, and kinetics of infection. However, as shown by radioimmunoprecipitation assays, the cloned virus-infected cells express a full-length gp41 protein as predicted by the nucleotide sequence, whereas the wild-type parental strain expresses a truncated gp33 protein. Both the parental strain and the cloned virus possess a deletion encompassing the end of the nef gene within the U3 region which apparently does not affect their in vitro cytopathic and replicative capacities.
Assuntos
Deleção Cromossômica , Genes nef , Proteína gp41 do Envelope de HIV/metabolismo , HIV-2/genética , Síndrome da Imunodeficiência Adquirida/patologia , Animais , Clonagem Molecular , HIV-1/genética , HIV-1/ultraestrutura , HIV-2/ultraestrutura , Humanos , Cinética , Macaca , Mutação , Mapeamento por Restrição , Linfócitos T/microbiologia , Transfecção , Vírion/crescimento & desenvolvimentoRESUMO
It is now well established that cytokines are involved in the regulation of gene expression from HIV-1 LTR. The present study provides evidence that TNF-alpha stimulates HIV-1 gene expression and that the enhancer sequence within the HIV-1 LTR is involved in the stimulation. These results support the idea that immunologic stimulation and infection may trigger the development of clinical AIDS in individuals latently infected with HIV-1.