RESUMO
Human immunodeficiency virus type 1 variants belonging to subtype A, as well as recombinant gaga/engvB variants, derived from HIV-infected patients living in the Moscow and Perm Regions, were isolated and characterized. Intravenous administration of psychoactive drugs was a major risk factor of the infection for all the patients. All the examined isolates of HIV-1 types A and A/B were shown to be characterized by a low virus-specific activity and to be used as secondary CCR5 and CXCR4 protein receptors. The findings suggest that the domination of subtype A variant in this risk group is unassociated with fundamental differences in biological properties between the isolates of this subtype and recombinant viruses.
Assuntos
Genes env/genética , Variação Genética , Infecções por HIV/genética , HIV-1/genética , Abuso de Substâncias por Via Intravenosa/virologia , Sequência de Aminoácidos , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Masculino , Dados de Sequência Molecular , Federação Russa/epidemiologiaRESUMO
Antigen recognition by alphabeta T lymphocytes is mediated via the multisubunit TCR complex consisting of invariant CD3gamma,delta,epsilon and zeta chains associated with clonotypic TCRalpha and beta molecules. Charged amino acids located centrally within the TCRalpha transmembrane region are necessary and sufficient for assembly with the CD3deltaepsilon heterodimer. Previously, we have shown that deletion of 6-12 amino acids from the carboxy terminus of the TCRalpha-chain dramatically abrogates surface TCR expression, suggesting that the distal portion of the TCRalpha transmembrane region contains information that regulates the assembly and/or intracellular transport of TCR complexes. We have examined in more detail the molecular basis for reduced TCR expression in T cells bearing truncated TCRalpha chains. We found that in contrast to wild-type (wt), variant TCRalpha proteins missing the last nine C-terminal amino acids did not associate with core CD3gamma,delta,epsilon chains and were not assembled into disulphide-linked alphabeta heterodimers. The stability of newly synthesised wt and variant TCRalpha molecules was similar, showing that the abrogated surface TCR expression was not a consequence of impaired protein survival. Nevertheless, truncated TCRalpha chains still assembled with the chaperon protein calnexin in the endoplasmic reticulum, indicating that the distal portion of the TCRalpha transmembrane region is not essential for calnexin interaction. These data document a role for the distal portion of the TCRalpha transmembrane region in the assembly of TCR complexes and provide a molecular basis for reduced TCR expression in cells bearing truncated TCRalpha chains.
Assuntos
Receptores de Antígenos de Linfócitos T alfa-beta/química , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Linfócitos T/imunologia , Sequência de Aminoácidos , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Calnexina , Dissulfetos/química , Retículo Endoplasmático/metabolismo , Hibridomas , Dados de Sequência Molecular , Oligossacarídeos/metabolismo , Subunidades Proteicas , Complexo Receptor-CD3 de Antígeno de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Deleção de SequênciaRESUMO
Totarol is a diterpene compound extracted from the totara tree. Totarol and eight other diterpenes were found to potentiate methicillin, one reducing the minimum inhibitory concentration of methicillin against resistant Staphylococcus aureus 256-fold. Totarol did not inhibit the synthesis of DNA or peptidoglycan in S. aureus, but reduced the respiration rate by 70%. Under potentiation conditions, diterpenes had only a slight effect on the respiration rate, but had a significant effect on expression of PBP 2a. We conclude that the primary staphylococcal target for totarol is the respiratory chain, but that potentiation of methicillin by diterpenes is by interference with PBP 2a expression.