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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Viral vaccines which stimulate the humoral immune response in humans have been successful in preventing most of the known virus diseases except dengue fever, respiratory syncytial virus infections and HIV-1-related AIDS. Burke [1] raised a concern that anti-HIV-1 antibodies may add a risk factor to immunized individuals infected with HIV-1. An approach to develop HIV-1 vaccines capable of stimulating anti-HIV-1 cytotoxic T cells requires an understanding of the importance of epidermal and epithelial Langerhans cells (LC). These cells are professional antigen-presenting cells which express HLA class I and class II molecules. Epithelial LC are present in a specific layer in the skin, genitalia and gut and may be accessible to viral antigens by local application in a vehicle for transepithelial transport of viral proteins/peptides (designated "HIV-1 Peplotion vaccine"). This approach is supported by the reports that HIV-1 gp160 in ISCOM induced MHC class I CTL response [2], mixing of cationic lipids with viral proteins formed complexes which were delivered to cell cytoplasm and the degraded peptides stimulated CTLs by HLA class I mechanism [3] and viral proteins encapsulated in pH-sensitive liposomes administered to LC induced primary antiviral CTLs [4]. Current studies in our laboratory deal with (a) selection of the vehicle for transepidermal transport of peptides and the conditions for selective uptake by epidermal LC [5]; (b) computer analysis of HIV-1 proteins to detect the putative proteolytic cleavage peptides with amino acid motifs which allow association with different known HLA class I haplotype molecules on LCs and synthetic peptide uptake from "without" by LC. The "HIV-1 Peplotion vaccine", when developed, will be useful for continual stimulation of antiviral CTLs in uninfected individuals and HIV-1 carriers by repetitive application to skin, genitalia and gut. The "Peplotion vaccine" will be applied by vaccinees, will be affordable for all human-populations and, hopefully, will be highly efficient.
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PMID:"HIV-peplotion vaccine"--a novel approach to protection against AIDS by transepithelial transport of viral peptides to Langerhans cells for long-term antiviral CTL response. (A review). 880 38

Studies in both monkeys and humans have suggested that transient infection with HIV-1 can occur without provoking a measurable humoral immune response. The objective of this study was to look for genetic and immunologic correlates of transient HIV-1 infection in antibody-negative men from whom HIV-1 had been isolated. The distributions of MHC class I, class II, and TAP (transporter protein associated with antigen processing) region genes were compared between 23 persistently seronegative men from whom HIV-1 was isolated at least once (isol+/Ab-) and 137 men who seroconverted. A subset of 13 of the 23 isol+/Ab- men were compared to 27 seronegative men for distribution of CD25+CD4+ and CD25+CD8+ cells in the absence of exogenous immunologic stimulation. The prevalences of the TAP1.4, and a combination of TAP1.4, and TAP2.3 variants were significantly higher in the isol+/Ab- men. The proportion of CD8+ cells that expressed CD25+ antigen was also significantly higher in the isol+/Ab- men than in the seronegative men. We conclude that isol+/Ab- men may be genetically and immunologically distinct from HIV-1 susceptible men. We hypothesize that activated CD8+ cells may have cleared HIV-1 infection in these men through genetically mediated influences of the TAP genes on the presentation of peptides by HLA class I molecules.
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PMID:Persistently seronegative men from whom HIV-1 has been isolated are genetically and immunologically distinct. 881 41

Productive infection by the LAV strain has been demonstrated in T cell precursors at different stages of intrathymic development, while viral replication in thymic epithelial cells is still controversial. In this article we show that epithelial cell cultures derived from the medullary component of normal thymus are infectable by HTLV-IIIB virus through cell-free and lymphoid-mediated transmission. Free virus inoculum results in the integration of proviral copies undergoing poor replication, whereas lymphoid-mediated transmission leads to substantial viral expression and the production of viral progeny able to secondary infect lymphoid cells. Interleukin 6 production and phenotype changes (increased expression of MHC class I and ICAM-1) were induced in TE cells by contact with free virus or by adhesion to infected lymphoid cells. By contrast, NF-kappa B-binding activity on the HIV-1 LTR kappa B enhancer element was upregulated only by contact with infected lymphoid cells, but not with virus. The viral replication observed in TE cells after lymphoid-mediated transmission correlates with the upregulation of NF-kappa B-binding activity. Interleukin 6 increased production and phenotype changes and increased NF-kappa B-binding activity were also induced by adhesion to uninfected lymphoid cells, demonstrating that lymphoepithelial cell contacts can activate TE cells. These results demonstrate that thymic epithelial cells are permissive to HIV infection and that viral replication in this cell lineage can be modulated by intracellular signals delivered by adhesive contacts.
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PMID:HTLV type IIIB infection of human thymic epithelial cells: viral expression correlates with the induction of NF-kappa B-binding activity in cells activated by cell adhesion. 887 Aug 43

We have previously described the generation of HIV-1 V3-specific cytotoxic T-lymphocytes (CTL) responses in BALB/c (H-2d) mice following immunization with Ty-virus-like particles carrying the V3 loop of gp120 (V3-VLPs) without adjuvant. In this study the effects of various adjuvants on CTL induction by V3-VLPs was examined. Mice immunized with V3-VLPs formulated in aqueous-based adjuvants, Detox, gamma-inulin, galactosaminylmuramyl dipeptide and Chemivax generated V3-specific CTL responses, although at reduced levels when compared to the no adjuvant group. V3-VLPs prepared in Alhydrogel, algamulin or as an oil emulsion in SAF-MF failed to generate V3-specific CTL responses. The mechanism whereby alum prevented the induction of a CTL response was investigated further. Immunization with V3-VLPs prepared in non-saturating doses of alum or alum plus EDTA primed for strong CTL responses, indicating that free VLPs do, but alum-bound VLPs do not enter the MHC class I processing pathway of antigen-presenting cells (APCs). Furthermore, V3-VLPs with very low doses of alum led to an enhancement of the CTL response. The formulation of hybrid Ty-VLPs in oil based or precipitating adjuvants, therefore, inhibits access to the MHC class I processing pathway of APCs. The intact particulate structure of hybrid VLPs is therefore strictly necessary for CTL induction.
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PMID:The effects of adjuvants on CTL induction by V3:Ty-virus-like particles (V3-VLPs) in mice. 887 90

Previous reports have indicated that both dendritic cells and macrophages have the ability to induce cytotoxic T lymphocyte (CTL) and T helper (Th) cell responses in vivo. Dendritic cells process exogenous antigens conventionally for presentation on major histocompatibility complex (MHC) class II molecules. However, unconventional processing of exogenous antigens in vitro for presentation on MHC class I molecules is still an open question. In this study, we report that a cloned dendritic cell line (D2SC/1) is able to present cell debris-associated exogenous viral proteins to MHC class I-restricted CTL in vitro. The dendritic cell line was very efficient in processing recombinant lymphocytic choriomeningitis virus nucleoprotein (LCMV NP) and presenting the class I-restricted epitope to CTL primed in vivo. Peritoneal macrophages could also process the recombinant LCMV NP for subsequent MHC class I presentation, but were less efficient compared to the dendritic cells. Furthermore, recombinant yeast-derived virus-like particles carrying the HIV-1 V3 loop (V3-VLP), which are protenaceous and do not contain any lipid, were also found to be efficiently processed by the dendritic cell line for presentation of the class I-restricted epitope. These results clearly indicate that viral proteins, in particulate form or associated with cell debris, are processed by dendritic cells for CTL induction.
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PMID:Dendritic cells process exogenous viral proteins and virus-like particles for class I presentation to CD8+ cytotoxic T lymphocytes. 892 44

Infection of cats with feline immunodeficiency virus (FIV), a naturally occurring lentivirus infection of cats which causes an AIDS-like disease, has generated considerable interest as an animal model for HIV vaccination. This paper reports on experiments performed to examine the potential of a fixed infected cell vaccine to confer protection against intraperitoneal challenge with cell-free FIV. The cell vaccine was highly immunogenic and elicited antibody responses to virus core antigen, p24, high virus neutralizing (VN) antibody titres, and antibodies which recognized cellular components of the vaccine. Whilst protection, assessed by the inability to detect infectious virus by virus isolation or polymerase chain reaction, against homologous but not heterologous FIV isolates was apparent up to week 12 post-challenge, when cats were monitored longer up to week 50 post-challenge a breakthrough in vaccine protection against homologous virus was observed. Protection could not be correlated with levels of antibody to p24 or VN antibody titres. In contrast with simian immunodeficiency virus vaccine studies in macaques there was no clear evidence that antibodies recognizing cellular components of the vaccine, including MHC class I and II antigens, conferred any protective effect following challenge. These results indicate that long-term post-challenge monitoring for infection is essential in lentivirus vaccine trials.
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PMID:Vaccination with fixed feline immunodeficiency virus (FIV) infected cells: protection, breakthrough and specificity of response. 896 13

We have previously shown that the tat protein of HIV-1 can be used as a carrier to promote the intracellular delivery of heterologous proteins. Here we have tested if the tat-delivery technology can be used to direct MHC class I presentation of native protein, using ovalbumin (OVA) as a model system. We show that a tat-ovalbumin conjugate (tatOVA) can be delivered into cells and that subsequent processing and presentation occurs, resulting in effective and specific killing of these target cells by an OVA specific cytotoxic T-lymphocyte (CTL) line. Comparison with the E.G7 line that expresses the OVA gene indicates that tat-mediated delivery is as efficient as endogenous expression in this system. Tat-mediated antigenic protein delivery may be useful both as a research technique and, potentially, as a therapeutic or prophylactic vaccine.
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PMID:Tat-mediated protein delivery can facilitate MHC class I presentation of antigens. 897 Jan 66

Based on the similar effects of HIV-1 gp41 and human type I interferons on inhibition of lymphocyte proliferation and modulation of MHC class I and II molecule expression, we compared amino acid sequences of human interferons with HIV-1 gp41 and found sequence-similarity existing between gp41 and IFN-alpha. Anti-gp41-antibodies affinity-purified from sera of HIV-1-infected individuals (stage A) using rsgp41-Sepharose column could recognize human IFN-alpha in ELISA, but no antibody against IFN-alpha was detected if immunoglobulins were prepared in the same way from pooled HIV-negative serum. Besides, a sheep polyclonal anti-human IFN-alpha antibody bound weakly to recombinant soluble gp41 (rsgp41) of HIV-1IIIB. These results indicate that gp41 may share an immunological epitope with IFN-alpha. We examined 40 sera from healthy and asymptomatic HIV-1-infected individuals and AIDS-patients for IFN-alpha antibody levels by ELISA. The levels of anti-IFN-alpha antibody in sera from asymptomatic HIV-infected individuals (stage A, n = 6) was increased by about 150% in comparison with HIV-negative, but the antibody levels were obviously reduced in the case of symptomatic HIV-infected individuals (stage B, n = 7) and AIDS-patients (stage C, n = 7) in comparison with asymptomatic HIV-infected individuals (stage A). We suppose that the increased IFN-alpha-antibody level in HIV-1-infected individuals (stage A) may be due to this common immunological epitope and cross-reaction of antibodies to HIV-1 gp41 with IFN-alpha.
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PMID:Increased levels of antibodies against interferon-alpha in HIV-1 positive individuals may be explained by a common immunological epitope on the human interferon-alpha and HIV-1 gp41. 909 76

Genetic crosses produced NOD/LtSz mice doubly homozygous for the severe combined immunodeficiency (scid) mutation and the beta2m (B2m) null allele. Both NOD/LtSz-scid/scid and NOD/LtSz-scid/scid B2m(null) mice lacked mature lymphocytes and serum Ig. However, homozygosity for the B2m(null) allele also resulted in the absence of MHC class I expression, loss of NK cell activity, accumulation of iron in the liver, and rapid clearance of human IgG1. NOD/LtSz-scid/scid B2m(null) mice supported markedly elevated levels of human T cell engraftment, compared with NOD/LtSz-scid/scid control animals, following injection with human PBMC. The increased engraftment was associated with a major increase in the number of human CD4+ T cells. Following injection with 20 million human PBMC, levels of human CD4+ T cells in the peripheral blood and spleen of NOD/ LtSz-scid/scid B2m(null) mice were 6- to 7-fold higher than those in NOD/LtSz-scid/scid mice and >50-fold higher than those in C.B-17-scid/scid mice. The resulting normalization of CD4+/CD8+ ratios in NOD/LtSz-scid/scid B2m(null) mice is in sharp contrast to that observed in NOD/LtSz-scid/scid mice or in C.B-17-scid/scid mice. Circulating human IgG was cleared 6-fold more rapidly in NOD/LtSz-scid/scid B2m(null) mice than in NOD/LtSz-scid/scid mice. This rapid IgG clearance suggested a failure of the engrafted human lymphoid cells to maintain high circulating levels of human IgG. The higher levels of human CD4+ T cells and the normalization of the CD4:CD8 ratio that are observed in human PBMC-engrafted NOD/LtSz-scid/scid B2m(null) mice suggest that this system may be an excellent model for studies of HIV pathogenesis.
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PMID:Enhanced human CD4+ T cell engraftment in beta2-microglobulin-deficient NOD-scid mice. 910 18

The human immunodeficiency virus type 1 (HIV-1) vpu gene encodes a small integral membrane phosphoprotein with two established functions: degradation of the viral coreceptor CD4 in the endoplasmic reticulum (ER) and augmentation of virus particle release from the plasma membrane of HIV-1-infected cells. We show here that Vpu is also largely responsible for the previously observed decrease in the expression of major histocompatibility complex (MHC) class I molecules on the surface of HIV-1-infected cells. Cells infected with HIV-1 isolates that fail to express Vpu, or that express genetically modified forms of Vpu that no longer induce CD4 degradation, exhibit little downregulation of MHC class I molecules. The effect of Vpu on class I biogenesis was analyzed in more detail using a Vpu-expressing recombinant vaccinia virus (VV). VV-expressed Vpu induces the rapid loss of newly synthesized endogenous or VV-expressed class I heavy chains in the ER, detectable either biochemically or by reduced cell surface expression. This effect is of similar rapidity and magnitude as the VV-expressed Vpu-induced degradation of CD4. Vpu had no discernible effects on cell surface expression of VV-expressed mouse CD54, demonstrating the selectivity of its effects on CD4 and class I heavy chains. VV-expressed Vpu does not detectably affect class I molecules that have been exported from the ER. The detrimental effects of Vpu on class I molecules could be distinguished from those caused by VV-expressed herpes virus protein ICP47, which acts by decreasing the supply of cytosolic peptides to class I molecules, indicating that Vpu functions in a distinct manner from ICP47. Based on these findings, we propose that Vpu-induced downregulation of class I molecules may be an important factor in the evolutionary selection of the HIV-1-specific vpu gene by contributing to the inability of CD8+ T cells to eradicate HIV-1 from infected individuals.
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PMID:The human immunodeficiency virus type 1 (HIV-1) Vpu protein interferes with an early step in the biosynthesis of major histocompatibility complex (MHC) class I molecules. 910 16


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