ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Immunization with an inactivated whole-virus vaccine is highly effective in preventing lentivirus infection. The viral protein(s) essential to the induction of protective responses, however, have not been identified. To define the role of virion components in the induction of protective immunity, we evaluated the efficacy of glycoprotein-enriched and glycoprotein-depleted simian immunodeficiency virus (SIV) subunit vaccines prepared by lentil-lectin affinity chromatography of gradient-purified virions using the immunization and challenge regimen previously found successful with an inactivated whole-virus vaccine. Infection was determined by successful recovery of virus, the induction of SIV-specific antibody responses, and infection of naive recipients by inoculation with lymph-node-derived lymphocytes from the vaccinates. Immunization with the glycoprotein-enriched preparation prevented infection in two out of four monkeys, whereas the glycoprotein-depleted vaccine failed to prevent infection in all four vaccinates tested. However, the glycoprotein-depleted vaccine appeared to moderate the progression of SIV-induced disease compared with non-immunized infected control monkeys inoculated with the same challenge dose. These data suggest that subunit vaccines containing sufficient quantities of viral glycoproteins can protect against SIV infection, whereas subunit vaccines composed predominantly of viral core proteins cannot. The development of effective vaccines against HIV infection should include studies on the optimum presentation of the viral envelope glycoproteins to produce long -term broadly protective immune responses.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Reactivation of latent HIV-1 is believed to play a major role in the pathogenesis of AIDS. Here we show that sodium butyrate (NaB), which can cause gene induction or cell differentiation, reactivates dormant HIV-1in vitroin chronically infected cells of T-lymphoid and monocytoid origin. The effect of NaB on HIV-1 expression in T-lymphoid cells was apparent 3h after addition of drug and peaked at 24 h. During this time the proportion of HIV-1 antigen expressing cells increased from < 0.5 to > 90%, and virus production increased by three orders of magnitude. The virus released by the NaB-induced cells was infectious. The extent and kinetics of NaB effects were similar to effects of phorbol 12-myristate 13-acetate in T cells, but not monocytes. Transient expression assays using an indicator gene under the control of the HIV-1 long terminal repeat revealed that mutations which altered the nucleotide sequence in the TATA box significantly reduced the NaB effect. These data show that NaB is a potent inducer of dormant HIV-1 and suggest that the TATA motif is required for this activity.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The pathogenesis of the HIV-associated lymphomas is not well understood. In order to begin characterizing this class of lymphoma, we initiated a molecular genetic study of DNA extracted from 31 diagnostic biopsy specimens from patients diagnosed with AIDS-associated non-Hodgkin's lymphoma. Analysis of 25 peripheral lymphomas showed that 14 were monoclonal B-cell processes, while 11 appeared to be of polyclonal origin. Five of the 14 monoclonal lymphomas were found to have rearrangements of the c-myc gene. Epstein-Barr virus (EBV) genomes were found in seven out of 14 monoclonal samples, but only two out of nine polyclonal samples. The six primary central nervous system (CNS) lymphoma samples were more homogeneous than the peripheral samples and all were monoclonal, positive for EBV and lacked detectable c-myc gene rearrangements. This study allows us to subdivide the HIV-associated lymphomas into three major molecular subtypes: (1) monoclonal B-cell process frequently associated with c-myc rearrangement or detectable EBV genomes, (2) polyclonal B-cell process typically without evidence of EBV, and (3) monoclonal primary CNS process associated with EBV genomes and lacking detectable c-myc rearrangement.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

A highly sensitive and reliable RNA polymerase chain reaction method has been developed which has been used to detect, quantify and sequence cell-free HIV RNA directly from the plasma of seropositive individuals. Plasma from 10 out of 12 haemophiliacs tested was found to contain detectable levels of HIV-1 RNA [log mean value: 1.2 × 103 copies for Centers for Disease Control (CDC) group II patients, 5.5 × 103 copies for CDC group IV patients]. The presence of cell-free circulating virus in both symptomatic and asymptomatic individuals suggests that viral replication continues throughout the course of infection. The same procedure has been used to detect and sequence HIV-1 RNA in two batches of unheated commercial factor VIII concentrate distributed in 1981 and 1983. The sequences obtained revealed a closer relationship to North American than to African strains of HIV-1.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We developed an assay for simultaneous amplification, detection and quantitation of HIV-1 gag gene and the DQ-α locus of the histocompatibility (HLA) region of the human genome by polymerase chain reaction (PCR). Crude cell lysates from control cell lines and peripheral blood mononuclear cells (PBMC) from HIV-1-infected and control individuals were coamplified using optimized concentrations of primers directed at both loci, followed by simultaneous hybridization with radioactively labeled HIV-1-gag and HLA-DQ-α probes. Simultaneous quantitation of the 242-base-pair HLA and 115-base-pair HIV products was accomplished by both end-point dilution analysis and image analysis of autoradiographs relative to standard curves derived from infected cell lines. We observed good agreement between input cell counts on fresh samples and the HLA-DQ-α target copy number values determined by both end-point dilution analysis and comparison of band intensities with standard curves. HIV-1 proviral load in symptomatic patients ranged from 200 to 4000 HIV-PCR-units per 1 × 106PBMC (mean of 1245 copies), whereas asymptomatic patients had levels ranging from two to 1000 HIV-PCR-units per 1 × 106PBMC (mean of 213 copies). This HIV/HLA coamplification approach should be particularly useful for analysis of frozen repository samples from natural history studies, and may facilitate wider application of quantitative PCR analysis.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The antiviral activity of 6–0-butanoylcastanospermine (MDL 28,574) [50% inhibitory concentration (IC50:1.1 μM)] in JM cells infected with a recent isolate of HIV-1 (GB8), was compared with other inhibitors of glycoprotein-processing enzymes. N-butyldeoxynojirimycin (BuDNJ), deoxynojirimycin (DNJ), castanospermine (CAST) or the reverse transcriptase inhibitor 2′3′-dideoxycytidine (ddC) had activities of 56, 560, 29 and 0.1 μM, respectively. MDL 28,574 was at least 50 times more active than BuDNJ and less active but better tolerated in cell culture than ddC, two compounds currently undergoing clinical trials. The CAST derivative showed good protection in H9 cells infected with HIV-1 (RF; IIIB; U455), and HIV-2 (ROD), although the potency was less than that seen in the JM/GB8 system. HIV-1 glycoproteins, gp160 and gp120, synthesized in H9 cells chronically infected with HIV-1 (RF) and treated with MDL 28,574, were characterized by an increase in relative molecular weight of approximately 7–8000 kD. The ratio of gp120 to gp160 was markedly reduced in treated cells and provided further evidence that cleavage of the gp160 precursor molecule is a major consequence of the inhibition of glycoprotein processing. The intracellular target for MDL 28,574 was verified as α-glucosidase-l of the processing enzymes by the analysis of high-glucose glycopeptides recovered from treated mouse cells. This activity correlated with the antiviral effect observed against the growth of a mouse retrovirus, Moloney murine leukemia virus (MOLV), in mouse cells.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We have previously hypothesized that an effective vaccine against HIV should elicit cell-mediated immunity without antiviral antibody production. As a first step towards this goal we have identified potential T-cell epitopes, without B-cell activity against the native protein, from the first and second conserved sequences, and from three functionally important regions of the HIV-1 envelope protein gp160. For this approach, short peptide sequences selected by established computer programs were synthesized and chemically modified to generate either polymers with disulfide bonds, or micelles with two palmitic acid residues attached to the amino-terminal lysine. In both configurations several peptides were immunogenic without the need for coupling to carrier molecules. Of the 19 peptides we tested in our present studies, seven induced good T-cell proliferative response in mice representing four major histocompatibility complex haplotypes. None of these seven peptides produced antibodies that could recognize the envelope protein gp160.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Breast-feeding as a route of HIV-1 transmission during infancy but also as a protective measure against early childhood morbidity has been investigated prospectively in children born to HIV-1-seropositive mothers and control children born to age- and parity-matched HIV-1 -seronegative women. The mothers of all study children had been enrolled antenatally at a maternity hospital in Kinshasa, Zaire, which served a relatively affluent group of women who sometimes chose not to breast-feed their infants. In 106 children born to HIV-1-seropositive women, the rate of HIV-1 transmission was 21% in 28 infants exclusively breast-fed, 19% in 68 infants both breast- and bottle-fed and 0% in 10 infants who were bottle-fed only (P = 0.35). In contrast, non-HIV-1-infected children of both HIV-1-seropositive and HIV-1-seronegative mothers who were exclusively breast-fed compared with uninfected children who were not exclusively breast-fed had significantly lower incidence rates of acute diarrhea, fever and lower respiratory tract infection. The lack of a dose-response effect between breast-feeding and perinatal HIV-1 transmission and the presence of a protective effect of breast-feeding against common causes of early childhood morbidity and mortality support the current World Health Organization recommendation that breast-feeding should continue to be promoted in all developing countries, including those with high HIV-1 prevalence rates in women of childbearing age.

ISSN:0269-9370    

出版商:OVID    

年代:1991

数据来源: OVID