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1.
J Virol ; 73(10): 8201-15, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10482571

RESUMO

We previously showed that envelope (gp160)-based vaccines, used in a live recombinant virus priming and subunit protein boosting regimen, protected macaques against intravenous and intrarectal challenges with the homologous simian immunodeficiency virus SIVmne clone E11S. However, the breadth of protection appears to be limited, since the vaccines were only partially effective against intravenous challenge by the uncloned SIVmne. To examine factors that could affect the breadth and the efficacy of this immunization approach, we studied (i) the effect of priming by recombinant vaccinia virus; (ii) the role of surface antigen gp130; and (iii) the role of core antigens (Gag and Pol) in eliciting protective immunity. Results indicate that (i) priming with recombinant vaccinia virus was more effective than subunit antigen in eliciting protective responses; (ii) while both gp130 and gp160 elicited similar levels of SIV-specific antibodies, gp130 was not as effective as gp160 in protection, indicating a possible role for the transmembrane protein in presenting functionally important epitopes; and (iii) although animals immunized with core antigens failed to generate any neutralizing antibody and were infected upon challenge, their virus load was 50- to 100-fold lower than that of the controls, suggesting the importance of cellular immunity or other core-specific immune responses in controlling acute infection. Complete protection against intravenous infection by the pathogenic uncloned SIVmne was achieved by immunization with both the envelope and the core antigens. These results indicate that immune responses to both antigens may contribute to protection and thus argue for the inclusion of multiple antigens in recombinant vaccine designs.


Assuntos
Antígenos Virais/imunologia , Produtos do Gene env/imunologia , Vacinas contra a SAIDS/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia/imunologia , Animais , Imunidade , Imunização , Macaca
2.
J Med Primatol ; 25(3): 201-9, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8892041

RESUMO

We explored the relationship between T cell activation signals and dendritic cells (DC) in the replication cycle of immunodeficiency viruses. First we analyzed the effect of two cell cycle inhibitors (mimosine and aphidicolin) on SIV reverse transcription, circularization, and integration in macaque resting T cells stimulated with anti-CD3 mAb at the time of infection. The formation of SIV LTR circles was blocked by the G1 inhibitor mimosine. The G1/S inhibitor aphidicolin neither affected circularization nor integration of SIV DNA. Therefore, the induction of SIV LTR circle production is likely to be mediated by signaling events normally regulating the G1 to S transition. We further characterized DC-dependent HIV-expression in human T cells. We examined the effect of ligating two novel receptors, IPO-3 and Bgp95, on DC-dependent HIV-1 expression. Activation of DCs through IPO-3 receptors, and to a lesser extent Bgp95 ligation, upregulated HIV spread in these cells. The mechanisms by which IPO-3 vs. Bgp95 increase HIV-1 levels appear to be different. In particular, IPO-3 ligation alone on T cells also increased HIV-1 levels. Activation of T cells via defined surface receptors or with DCs is required for establishing HIV/SIV cDNA synthesis in T cells.


Assuntos
DNA Viral/biossíntese , Células Dendríticas/imunologia , HIV/fisiologia , Ativação Linfocitária , Vírus da Imunodeficiência Símia/fisiologia , Linfócitos T/imunologia , Linfócitos T/virologia , Replicação Viral , Animais , Afidicolina/farmacologia , Ciclo Celular/efeitos dos fármacos , Replicação do DNA , DNA Complementar/biossíntese , Citometria de Fluxo , HIV/isolamento & purificação , HIV/patogenicidade , Humanos , Macaca mulatta , Mimosina/farmacologia , Reação em Cadeia da Polimerase , DNA Polimerase Dirigida por RNA/metabolismo , Sequências Repetitivas de Ácido Nucleico , Transdução de Sinais , Vírus da Imunodeficiência Símia/genética , Linfócitos T/citologia , Integração Viral
3.
J Exp Med ; 182(2): 617-21, 1995 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-7629519

RESUMO

Although immunodeficiency viruses can enter resting CD4+ T lymphocytes, activation of T cells is required for complete viral cDNA synthesis and transport of double-stranded viral DNA to the nucleus. Cross-linking T cell receptors (TCRs) on resting CD4+ T cells induces reverse transcription of full-length simian immunodeficiency virus (SIV) genomes, but TCR engagement alone is insufficient to stimulate SIV DNA to move to the nucleus and form long terminal repeat (LTR) circles. Neither ligation of TCR or CD28 receptors nor interleukin 2 (IL-2) alone induces formation of LTR circles; however, the combination of TCR ligation with either CD28 ligation or IL-2 doses. Anti-IL-2 serum inhibits the formation of LTR circles induced by cross-linking CD3 and CD28, but has no effect on the induction of increased viral reverse transcription. Thus, two signals appear to be required for immunodeficiency viruses to move to the T cell nucleus, one from the TCR to promote reverse transcription of the viral genome, the other through an IL-2-dependent process leading to formation of LTR circles.


Assuntos
DNA Viral/genética , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Interleucina-2/farmacologia , Ativação Linfocitária , Receptores de Antígenos de Linfócitos T/fisiologia , Vírus da Imunodeficiência Símia/genética , Linfócitos T/microbiologia , Animais , Antígenos CD28/fisiologia , Núcleo Celular/microbiologia , Técnicas In Vitro , Macaca nemestrina , Sequências Repetitivas de Ácido Nucleico , Replicação Viral/efeitos dos fármacos
4.
Adv Exp Med Biol ; 378: 461-3, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8526118

RESUMO

We investigated the role of blood dendritic cells (DC) in transmission of HIV-1 from infected to uninfected CD4+ T cells, and the accessory molecules involved. DC promoted transmission from infected to uninfected CD4+ cells, but blood DC themselves were not infectable. DC-mediated transmission was blocked by mAb to CD4 and MHC class II, but strongly increased by mAb to CD40 on DC or CD28 on T cells. The DC-dependent infection was inhibitable by anti-CD80 and a soluble fusion protein of the CD80 ligand, CTLA4; soluble CTLA4Ig also blocked infection augmented by crosslinking CD40. We also demonstrated that mAb to CD40 up-regulate the expression of CTLA4 ligands CD80 and B70/B7-2 (CD86) on DC. These data suggest that the dialog between CD40-CD40 ligand (CD40L) and CD28-CD80 counter-receptors on DC and T cells may be linked to HIV infection in vivo.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Células Dendríticas/imunologia , Células Dendríticas/virologia , HIV-1/patogenicidade , Imunoconjugados , Abatacepte , Anticorpos Bloqueadores/farmacologia , Anticorpos Monoclonais/farmacologia , Antígenos CD/metabolismo , Antígenos de Diferenciação/metabolismo , Antígeno B7-1/metabolismo , Antígeno B7-2 , Células Sanguíneas/imunologia , Células Sanguíneas/virologia , Antígenos CD28/metabolismo , Antígenos CD40/metabolismo , Ligante de CD40 , Antígeno CTLA-4 , Comunicação Celular , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Técnicas In Vitro , Ligantes , Glicoproteínas de Membrana/metabolismo , Regulação para Cima , Replicação Viral
5.
Immunity ; 1(4): 317-25, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7534204

RESUMO

We investigated the role of blood dendritic cells (DCs) in transmission of HIV-1 from infected to uninfected CD4+ T cells, and the accessory molecules involved. DCs promoted transmission from infected to uninfected CD4+ cells, but DCs themselves were not infectable. DC-mediated transmission was blocked by MAb to CD4 and MHC class II, but strongly increased by MAb to CD40 on DCs or CD28 on T cells. The DC-dependent infection was inhibitable by anti-CD80 and a soluble fusion protein of the CD80 ligand, CTLA4; soluble CTLA4 immunoglobulin also blocked infection augmented by cross-linking CD40. These data suggest a linkage between CD40-CD40L and CD28-CD80 counterreceptors on DCs and T cells, and spread of HIV infection in vivo.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos B/metabolismo , Antígeno B7-1/metabolismo , Células Dendríticas/imunologia , Infecções por HIV/imunologia , HIV-1 , Anticorpos Monoclonais , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/virologia , Antígenos CD28/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Antígenos CD40 , DNA Viral/biossíntese , Células Dendríticas/virologia , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Técnicas In Vitro , Regulação para Cima , Replicação Viral
6.
J Virol ; 67(12): 7008-16, 1993 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8230425

RESUMO

The relationship between T-cell activation and early events in the replication cycle of simian immunodeficiency virus (SIV) was analyzed in resting T lymphocytes from macaques. We used the polymerase chain reaction to detect an early product of reverse transcription (R/U5) and almost complete viral DNA (long terminal repeat/gag). We found that SIV can enter resting T lymphocytes and initiate replication but that the reverse transcription process is not efficient and proceeds slowly in resting cells. Cross-linking the CD3/T-cell receptor complex with monoclonal antibodies, unlike cross-linking either the CD28 or CD2 accessory receptor and like phorbol myristate acetate, induced a rapid increase in viral R/U5 DNA detected within 3 to 6 h postinfection. Anti-CD3 or phorbol myristate acetate induced replication of full-length viral DNA within 6 to 9 h postinfection, but full-length SIV DNA was not detectable at earlier time points. We then compared various inhibitors of T-cell activation for their effects on viral initiation and complete replication. Cyclosporin A, an inhibitor of a distal step in T-cell activation, blocked anti-CD3-induced T-cell proliferation and completion of SIV DNA replication but had no effect on induced increases in SIV R/U5 DNA. By contrast, initial SIV DNA synthesis was partially blocked by inhibitors of very early steps in T-cell activation, including herbimycin A, an inhibitor of protein tyrosine kinases, and by two different inhibitors of protein kinase C, H7 and staurosporine. Since resting T cells do not efficiently complete SIV DNA synthesis and cyclosporin A can block the formation of complete viral DNA induced in activated T cells, a cellular factor(s) present in activated T cells appears to be required for the formation of full-length SIV DNA.


Assuntos
DNA Viral/biossíntese , Ativação Linfocitária , Vírus da Imunodeficiência Símia/crescimento & desenvolvimento , Linfócitos T/microbiologia , Animais , Benzoquinonas , Complexo CD3/metabolismo , Divisão Celular , Células Cultivadas , Ciclosporina/farmacologia , Humanos , Interleucina-2/biossíntese , Lactamas Macrocíclicas , Ativação Linfocitária/efeitos dos fármacos , Macaca nemestrina , Proteína Quinase C/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Quinonas/farmacologia , Receptores de Antígenos/metabolismo , Rifabutina/análogos & derivados , Transdução de Sinais , Acetato de Tetradecanoilforbol/farmacologia
7.
Am J Vet Res ; 48(6): 984-7, 1987 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-3037953

RESUMO

A sensitive and specific procedure for the detection of Argentine isolates of bovine herpesvirus-1 was developed. The procedure was based on a dot-blot, nucleic acid hybridization, using 32P, nick-translated, plasmidic probes. The probes contained cloned Bam H1 restriction fragments in the left half of the viral genome. The detection limit of the procedure was 10 pg of viral DNA.


Assuntos
DNA Viral/análise , Herpesvirus Bovino 1/genética , Animais , Sequência de Bases , Bovinos , Clonagem Molecular , Enzimas de Restrição do DNA , Desoxirribonuclease BamHI , Desoxirribonuclease EcoRI , Hibridização de Ácido Nucleico , Plasmídeos
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