RESUMEN
OBJECTIVE: To determine whether the peptide glycyl-prolyl-glycine amide (GPG-NH2) corresponding to a conserved motif in the tip of the third hypervariable region of gp120 affected the early events in the human immunodeficiency virus type 1 (HIV-1) replication. DESIGN/METHODS: Glycyl-prolyl-glycine amide was tested for its effect on HIV-1 adsorption, co-receptor usage, proviral DNA synthesis, messenger RNA (mRNA) synthesis and splicing, translation, tat/TAR transactivation, and virus protease activity. RESULTS: Glycyl-prolyl-glycine amide did not appear to affect the early events of the virus replication. HIV-1 having glycine-leucine-glycine instead of GPG in the V3 loop and the mutants deleted of the GPG motif were still inhibited by the peptide. Glycyl-prolyl-glycine-NH2 had no discernible effect on any of the other steps in the virus replication cycle tested. The only effect observed was an increased sodium dodecyl sulfate polyacrylamide amide gel electrophoresis mobility of gp160/120 at high concentrations of GPG-NH2. CONCLUSIONS: The tripeptide GPG-NH2 is a nontoxic compound that inhibits the replication of HIV-1 by an apparently new mode of action.
Asunto(s)
Amidas/farmacología , Proteína gp120 de Envoltorio del VIH/química , VIH-1/efectos de los fármacos , Oligopéptidos/farmacología , Fragmentos de Péptidos/química , Replicación Viral/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , ADN Viral/biosíntesis , Expresión Génica , Productos del Gen env/genética , Productos del Gen gag/genética , Productos del Gen tat/metabolismo , Proteína p24 del Núcleo del VIH/análisis , Proteína gp120 de Envoltorio del VIH/metabolismo , Proteína gp120 de Envoltorio del VIH/farmacología , Duplicado del Terminal Largo de VIH , Proteasa del VIH/metabolismo , VIH-1/genética , VIH-1/metabolismo , VIH-1/fisiología , Células HeLa , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/virología , Fragmentos de Péptidos/farmacología , ARN Viral , Proteínas Recombinantes de Fusión/metabolismo , Activación Transcripcional , Productos del Gen tat del Virus de la Inmunodeficiencia HumanaRESUMEN
Eighteen virus isolates and 22 serum samples collected between 1971 and 1997 from patients with mumps were genotyped by PCR with specific primer pairs for the A, C and D genotypes of the small hydrophobic (SH) protein gene. All serum samples were subjected to nucleotide sequence analysis of the gene, and the deduced 57-amino-acid sequences were aligned with previously published sequences from the USA, Canada, Portugal, the UK, France, Germany, Switzerland, Denmark, Sweden, Russia, China and Japan. The existence of six genotypes of the SH protein gene, named A to F, was confirmed. In the Stockholm area, co-circulation of genotypes A, C and D at different times was found. There was a striking difference in genotype between the virus isolates and the serum samples. The 18 virus isolates represented genotypes C and D, whereas the 22 serum samples contained genotype A. In most cases, the amino acid sequences of the 22 genotype A specimens were identical to the previously described SBL-1 strain of genotype A. Genotypes C and D were always associated with meningitis, and in some cases parotitis, whereas infection with genotype A most often resulted in parotitis and seldom in meningitis.