ISSN:0889-2229    

DOI:10.1089/aid.1997.13.367

年代:1997

数据来源: MAL

摘要:

Studies from a number of laboratories have shown the presence of a factor(s) in whole, parotid, and submandibular human saliva capable of inhibiting HIV-1 infecti vityin vitro. Data from our laboratory suggested that the level of anti-HIV-1 activity is higher in submandibular than parotid or whole saliva. Previous results obtained with pooled submandibular saliva from seronegative individuals included a filtration step following saliva-virus interaction. In this article, we present data on the HIV-1-inhibitory activity of individual submandibular saliva samples collected from 15 donors. We show that although anti-HIV activity is quantitatively similar in most individuals (9 of 15), some (4 of 15) are much less active than others and some (2 of 15) lack inhibitory activity. We also show that for most individuals the level of anti-HIV inhibitor is similar with or without a filtration step. However, 2 of the 15 samples demonstrated activity only after filtration. The quantitative and qualitative anti-HIV activity of individual saliva samples appeared to reflect differences in the individual donors. We further show that the anti-HIV activity of submandibular saliva is demonstrated not only against laboratory strains of HIV-1 but is similarly active against three clinical HIV-1 isolates. In contrast, submandibular saliva had little effect on the infectivity of HIV-2 or SIV.

ISSN:0889-2229    

DOI:10.1089/aid.1997.13.371

年代:1997

数据来源: MAL

摘要:

Following resolution of a primary HIV-1 infection initially induced by inoculating a mixture of three different virus strains, a chimpanzee was exposed to both immunostimulatory and immunosuppressive agents in an attempt to assess the contributions of different components of the immune system in suppressing circulating virus. The infusion of human leukocytes as an xenogeneic stimulus induced the replication of one of the input virus strains that had not previously been isolated or detected by PCR. The administration of high-dose, 17-day courses of corticosteroids resulted in coordinate and transient increases of each of the three viruses present in the original inoculum and elevation of HIV-1-specific ELISA antibody levels. Steroids administered to a second chimpanzee, chronically infected with a single HIV-1 isolate, also induced elevations of cell-associated virus. These results highlight the intimate relationship between immune system activation/immuno-suppression and HIV replication in an animal model.

ISSN:0889-2229    

DOI:10.1089/aid.1997.13.377

年代:1997

数据来源: MAL

摘要:

Mitogen-activated T cell lines may be reproducibly used to identify relatively conserved HIV-1 epitopes that dominate CTL recognition of HIV-infected cells. Using a combination of nested truncations of HIV-vaccinia recombinants encoding HIV-1LAIEnv and overlapping peptides that span the coding regions of the HIV-1 SF2 subclone ofenv, gag, nef, rev, andtat, we have mapped the immunodominant, relatively conserved CTL epitopes recognized by 25 HIV-seropositive individuals with CD4 counts between 100 and 500/mm3and no history of AIDS opportunistic infection. We could characterize at least 1 peptide CTL epitope recognized by the T cell lines of 18 of 25 of the subjects; the T cell lines from 2 additional subjects recognized HIV-vaccinia presenting targets, but no dominant peptide epitope was identified. CTL epitopes were most frequently encoded bygag(recognized by 16 of 25 patient T cell lines), followed bynefandenv(11 of 25 each), and the RT region ofpol(9 of 25). Tat and Rev were rarely the sites of CTL epitopes. The identified epitopes occurred predominantly in relatively conserved regions of HIV-1. The mean number of HIV peptides identified at a single time for each cell line was 2.7 ± 1.7. Although no single peptide dominated CTL recognition in more than four individuals, clusters of epitopes were found in the N-terminal region of gp160 and in two central regions of Nef. The dominant HIV-1 CTL epitopes in infected patients were not predictable on the basis of MHC expression and varied widely in an MHC-diverse population

ISSN:0889-2229    

DOI:10.1089/aid.1997.13.383

年代:1997

数据来源: MAL

摘要:

Gag-specific immune responses and changes in HIV-1 RNA levels were evaluated in eight HIV-1-infected persons, in order to assess the immunotherapeutic potential of HIV-1 pl7/p24: Ty virus-like particles (p24-VLP). All treated subjects showed transient and dose-dependent proliferative responses to the Ty-VLP carrier (stimulation index [SI], 2.0-119.5). Three of four individuals who received either 500 or 1000 μg of p24-VLP also showed proliferative responses to pl7 or p24 (SI, 2.0-15.7). In 2 subjects who were treated with either 500 or 1000 μg of p24-VLP, enhanced Gag-specific CTL precursor (CTLp) frequencies were observed after immunization (10- to 14-fold). Both subjects had low baseline Gag-specific CTL activity (<25 CTLp/106PBMCs). In the other participants studied no significant boosting of preexisting Gag-specific CTL responses was observed. Short-term elevation of HIV-1 RNA levels at weeks 2 and 4 was observed in two subjects treated with the highest dose of p24-VLP. However, HIV-1 RNA levels at week 24 did not significantly differ from those found in the placebo group. In conclusion, p24-VLP induced marginal Gag-specific immune responses in limited numbers of HIV-1-seropositive individuals, with some showing transient elevation of HIV-1 viral load. Further studies are needed to establish potential clinical effects of these observation

ISSN:0889-2229    

DOI:10.1089/aid.1997.13.393

年代:1997

数据来源: MAL

ISSN:0889-2229    

DOI:10.1089/aid.1997.13.401

年代:1997

数据来源: MAL

摘要:

Direct inoculation of genetic material in DNA form is a novel approach to vaccination that has proved efficacious for a number of viral agents. We are interested in the potential of this approach for the delivery of vaccines based on attenuated or replication-defective retroviruses. Toward this goal, we tested the effect of intramuscular inoculation of a plasmid containing the entire genome of feline immunodeficiency virus (FIV-Petaluma, F14 clone). DNA delivery was compared with intramuscular or intraperitoneal inoculation of virus reconstituted from the same molecular clone. The outcome was monitored by serological analysis and quantitative virus load determination over a 31-week period. DNA inoculation was found to be a reliable means of infection, although seroconversion and the rise in PBMC virus load were delayed relative to intramuscular or intraperitoneal inoculation of virus. At 31 weeks, similar levels of proviral DNA were detected in central lymphoid tissue of all infected animals. In conclusion, DNA inoculation of proviral DNA will be of use as a novel method of cell-free virus challenge and may have further potential for the delivery of lentiviral vaccines.

ISSN:0889-2229    

DOI:10.1089/aid.1997.13.405

年代:1997

数据来源: MAL

摘要:

Focal and segmental glomerulosclerosis (FSG) with endothelial tubuloreticular inclusions (TRIs) is the typical lesion of human HIV-associated glomerulopathy. Autopsy studies showed the presence of FSG in 3 of 15 macaques dying 15–120 weeks after experimental infection with a simian immunodeficiency virus (SIVMne). Ultrastructural studies generally revealed numerous endothelial TRIs (also present in normals), mesangial expansion, and evidence of mesangial cell injury. One additional animal had a small-vessel polyarteritis with a proliferative and focally crescentic glomerulonephritis; seven animals had mild, multifocal interstitial nephritis. All animals had documented viremia after infection; 14 of 15 developed antibodies to SIV postinoculation. Additional postmortem findings included severe enterocolitis, encephalitis, and opportunistic infections. In contrast, autopsy studies of macaques infected with a type D simian retrovirus (S AIDS-D/Washington, SRV-2) for similar periods of time (n= 40) showed no evidence of FSG. One SRV-infected animal had a mild proliferative glomerulonephritis. These studies indicate SIV-infected primates may provide a relevant model for study of human HIV-associated nephropathy. They also indicate the variable pathology that can be seen in primate infections of distinct retrovirus types, each of which produces a simian immunodeficiency state that resembles human AID

ISSN:0889-2229    

DOI:10.1089/aid.1997.13.413

年代:1997

数据来源: MAL

摘要:

A single protein of 12 kDa, p12 is encoded by the HTLV-I genome from both the singly spliced mRNA pX-ORF-I and doubly spliced mRNA pX-rex-ORF-I. While many full-length sequences of HTLV-1 are known, data on the p12 region of African STLV-I are unavailable. We have undertaken to sequence the p12 gene in STLV-I from Central and West African naturally infected primates, and have compared them to known p12 sequences of HTLV-I.Our data on sequence andin vitrotranscription-translation analyses indicate that p12 is a 91-amino acid (aa) protein among STLV-I strains from Central and West Africa, in contrast to the 99-aa protein found among HTLV-I strains around the globe. The p12 sequences of STLV-I exhibit a marked genetic variability at the level of both nucleotide and peptide sequences. Hydropathic and helical wheel analyses reveal that 60% of residues in HTLV-I p12 are hydrophobic, in contrast to 55% in STLV-I from Africa. Although HTLV-I and STLV-I show a similar putative antigenic site, a second potential site was located exclusively in STLV-I from Africa. There are differences in the predicted transmembrane domains in p12 between STLV-I and HTLV-I. Furthermore, the secondary structure data according to the Chou and Fasman algorithm predict an α-helical domain at the carboxy terminus in HTLV-I, and this domain may be truncated in STLV-I p12. The amino acid sequence of p12 shows two leucine zipper motifs (LZMs) at the amino terminus and in the middle region, respectively. This is the first report describing the size differences in p12 protein between HTLV-I and STLV-I, which may provide insights into pathogenic mechanisms used by HTLV-I and STLV-I

ISSN:0889-2229    

DOI:10.1089/aid.1997.13.425

年代:1997

数据来源: MAL

摘要:

Asymptomatic infection of macaques with simian retroviruses type D (SRV/D), the etiologic agents of one form of retrovirus-induced simian immunodeficiency disease, can confound experiments with the simian immunodeficiency virus (SIV), which also induces immunodeficiency disease in macaques. The SIV/macaque model is the preferred nonhuman primate model for AIDS-related research. Serological screening for SRV/D alone is insufficient because not all infected animals seroconvert, and virus isolation by cocultivation may require 4 to 6 weeks. We have established a DNA polymerase chain reaction (PCR) assay. One set of nested primers allows detection of SRV/D serotypes 1, 2, and 3 and distinguishes SRV-2 from the other two serotypes. The PCR assay is sensitive; a single proviral copy of SRV/D could be detected in 150,000 to 210,000 macaque peripheral blood mononuclear cells (PBMCs). When applied to a panel of virus isolation-positive macaque samples, the PCR assay was positive in 100% of the tests. No false-positive results were seen when known specific-pathogen-free (SPF) macaques were examined. We propose that macaques be screened with a combination of SRV/D serology and this DNA PCR assay prior to enrollment in experiments with SIV.

ISSN:0889-2229    

DOI:10.1089/aid.1997.13.433

年代:1997

数据来源: MAL