摘要:

ObjectiveTo determine whether short peptides corresponding to the RGPGR motif of the V3 loop of gp120 have anti-human immunodeficiency virus type 1 (anti–HIV-1) activity.Design/MethodsShort peptides were tested against the HIV-1 laboratory strains and clinical isolates.ResultsThe tripeptide glycyl–prolyl–glycine amide (GPG-NH2) inhibited the replication of both laboratory strains and 47 clinical isolates, including 19 strains that were resistant to other drugs or that were from patients with failing therapy. The 50% inhibitory concentrations values were 2.7 to 37 &mgr;M. Phenotypic change of two isolates from nonsyncytia-inducing to syncytia-inducing did not change their sensitivity to GPG-NH2. The tripeptide added to the antiviral effect of both zidovudine and ritonavir.ConclusionsThe tripeptide GPG-NH2is a nontoxic compound that inhibits the replication of HIV-1 by an apparently new mode of action. Glycyl–prolyl–glycine-NH2might prove useful by itself or as a lead compound for the treatment of drug-resistant HIV-1. Glycyl–prolyl–glycine-NH2is currently undergoing phase I/II human clinical trials in Sweden.

ISSN:1090-9508    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo 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/MethodsGlycyl–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.ResultsGlycyl–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-NH2had 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.ConclusionsThe tripeptide GPG-NH2is a nontoxic compound that inhibits the replication of HIV-1 by an apparently new mode of action.

ISSN:1090-9508    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo determine whether genotypes from human immunodeficiency virus type 1 (HIV-1) subtypes A, C, or D or intersubtype recombinants have the same probability of being transmitted from mother to child.MethodsWe determined the HIV-1 genetic subtype and maternal risk factors of 51 matched transmitting and nontransmitting mothers from Tanzania. The HIV-1gag(p24–p7) andenv(C2–C5) nucleotide sequences were used for genotype classification, and matched logistic regression analysis was used to assess differences among genotypes.ResultsMothers infected with HIV-1 subtype A (odds ratio, 3.8; 95% CI, 0.8–24.7%), HIV-1 subtype C (odds ratio, 5.1; 95% CI, 1.3–30.8%), or HIV-1 intersubtype recombinant viruses (odds ratio, 5.3; 95% CI, 1.2–33.4%) were more likely to transmit HIV-1 to their infants than mothers infected with HIV-1 subtype D. Lower CD4 cell counts at enrollment were associated with transmission, but CD4 cell counts within each genotype did not explain differences in transmission among HIV-1 genotypes.ConclusionWe have shown that HIV-1 genotypes might be associated with differential risk for vertical transmission. These findings provide the first evidence that HIV-1 genetic subtypes may play a role in rates of vertical transmission in an African setting.

ISSN:1090-9508    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesThis work focuses on human cytomegalovirus (HCMV) UL73, which encodes for a putative transmembrane glycoprotein that is highly conserved among herpesviruses.Study DesignpUL73 expression was analyzed both in transiently transfected and in HCMV-infected cells using a pUL73-specific antiserum by immunoblot and immunofluorescence. Sequencing analysis from several clinical isolates and laboratory-adapted strains was also performed.ResultspUL73 expressed in transiently transfected cells consists in a polypeptide of the expected size (15–18 kd) with cytoplasmic localization. In infected cells, pUL73 is expressed with true-late kinetics and localizes both in perinuclear granular formations and on the cell surface. A broad band (39–53 kd), sensitive to O-glycosidase digestion was detected in purified virus. In addition, sequence analysis showed that the N-terminal portion of pUL73 from clinical isolates is highly polymorphic.ConclusionsUL73 encodes for a new structural glycoprotein (gpUL73) expressed on the cell surface of infected cells and highly polymorphic among clinical isolates.

ISSN:1090-9508    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:1090-9508    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesWe compared the effect of priming with a synthetic oligodeoxynucleotide (ODN) immunostimulatory DNA sequence followed by vaccination with human immunodeficiency virus type 1 (HIV-1) in incomplete Freund's adjuvant (IFA) or HIV-1 antigen alone to the simultaneous administration of immunostimulatory sequences (ISS) with HIV-1 in IFA.MethodsWe examined immune function involving interferon-&ggr; (IFN-&ggr;) production, RANTES (regulated upon activation, normal T cell expressed and secreted) production, and lymphocyte proliferation, all of which appear to be augmented in HIV-1–exposed, but uninfected, individuals.ResultsWe demonstrate that similar levels of antigen-specific IFN-&ggr; were produced from lymph node cells of the animals immunized with HIV-1 antigen in IFA containing the CpG ODN 1826 (ISS; mean ± SE = 450.8 ± 224.3 pg/mL) and the group of animals primed with the ODN before injection with the HIV-1 in IFA (mean ± SE = 377.7 ± 294.8 pg/mL) or HIV-1 antigen alone (IFN-&ggr; = 0 pg/mL). However, the group that received the HIV-1 in IFA plus ISS mounted a stronger lymphocyte proliferation (mean net ± SE = 29,180 ± 1,932 cpm) compared to the group primed with the ODN before injection with HIV-1 in IFA (mean net ± SE = 8,575 ± 2,978 cpm). Furthermore, the group that received the HIV-1 in IFA plus ISS also mounted stronger &bgr;-chemokine production measured as RANTES (mean ± SE = 1,217 ± 267.4 pg/mL) compared to the group that received the ODN before injection with HIV-1 in IFA (mean ± SE = 129.1 ± 48.5 pg/mL). Antibody responses from the group that received the HIV-1 in IFA plus ISS also showed a higher p24-specific response that was predominantly of the immunoglobulin G IgG2b isotype.ConclusionThese results suggest that the simultaneous administration of the ISS in the HIV-1 in IFA emulsion may be a condidate for testing in non-human primates and in human studies as a therapeutic and preventative vaccine.

ISSN:1090-9508    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesThis study investigates the potential impact of a bereavement support group on plasma viral load.MethodsA randomly selected subsample of human immunodeficiency virus type 1 (HIV-1)–positive homosexual men participating in a controlled clinical trial of a bereavement support group intervention was studied. The intervention consisted of one 90-minute group session per week for 10 weeks. The plasma HIV-1 RNA copy number was measured at baseline and after intervention (10 weeks) by the Roche AMPLICOR assay.ResultsThere was a significant effect of the intervention on the change on the plasma HIV-1 RNA copy number (limited control model, &bgr; = −0.49,p= 0.02; extended control model, &bgr; = −0.37,p= 0.01), independent of antiretroviral therapies; prophylactic therapies against potentially lethal HIV-1 associated conditions; CD4 cell count; viral load; and Centers for Disease Control and Prevention clinical disease stage at baseline.ConclusionsBereavement support group interventions may prove to be not only a primary therapy for psychologic distress after bereavement but also an adjunctive therapy for sustained control of plasma viral load in conjunction with highly active antiretroviral therapy in this population.

ISSN:1090-9508    

出版商:OVID    

年代:2001

数据来源: OVID