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Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following inactivated virus vaccination trials, the surface glycoprotein gp120 of the feline immunodeficiency virus (FIV) was considered as one of the determinants for protection. However, several vaccination trials using recombinant Env protein or some peptides failed to induce protection. To understand the role of the gp120 protein in vivo, we vaccinated cats with naked DNA coding for FIV structural proteins gp120 and p10. We analyzed the ability of these vaccinations to induce immune protection and to influence the onset of infection. Injection in cat muscles of expression vectors coding for the FIV gp120 protein induced a humoral response. Cats immunized twice with the gp120 gene showed different patterns after challenge. Two cats were, like the control cats, infected from the second week after infection onwards. The two others maintained a low proviral load with no modification of their antibody pattern. The immune response induced by gp120 DNA injection could control the level of viral replication. This protective-like immune response was not correlated to the humoral response. All the cats immunized with the gp120 gene followed by the p10 gene were infected, like the control cats, from the second week but they developed a complete humoral response against viral proteins after challenge. Furthermore, they showed a sudden but transient drop of the proviral load at 4 weeks after infection. Under these conditions, one injection of the p10 gene after one injection of the gp120 gene was not sufficient to stimulate protection. On the contrary, after a period, it seems to facilitate virus replication.
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PMID:DNA vaccination using expression vectors carrying FIV structural genes induces immune response against feline immunodeficiency virus. 926 51

We have attempted to purify envelope (Env) glycoproteins of human immunodeficiency virus (HIV) from the culture supernatants of CHO-Sec cells that secreted truncated 140-kDa precursor and mature 120-kDa Env glycoproteins. The concentrated culture supernatants were applied to a column coupled with cibacron blue 3GA (CB3GA) to separate albumin from the Env proteins because CB3GA, a triazine dye, has been known to have a high affinity to albumin. Unexpectedly, Env proteins as well as albumin bound to the column, and the bound Env proteins were eluted by increasing the ionic strength using KCl. Gp120 was eluted at 0.5-0.9 M of KCl, while a higher concentration (0.9-1.5 M) was necessary for the elution of gp140. The agarose gel coupled with reactive red 120 (RR120), another triazine dye with similar characteristics, also retained both Env proteins, and the bound Env proteins could be eluted in a similar manner. In addition, these agents inhibited syncytium formation caused by HTLV-IIIB and HTLV-IIIMN. Inhibition was also seen when a virus-free fusion assay between Env protein expressed in CHO cells and fluorescent labeled SupT1 cells were used. These findings indicate that triazine dyes bind to the functional regions of Env proteins of HIV-1 that play important role(s) for HIV infection.
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PMID:Triazine dyes inhibit HIV-1 entry by binding to envelope glycoproteins. 934 23

Recently, the presence of human immunodeficiency virus type 1 (HIV-1) RNA transcripts with negative-strand polarity has been shown in tissue culture models of acute and persistently infected cells. One of these transcripts encodes a 189 amino acid open reading frame. This highly conserved antisense sequence is complementary to the structured Rev-responsive element and extends through the cleavage site of the Env protein. We tested the ability of this antisense RNA to modulate HIV-1 replication and the mRNA profile when expressed stably or transiently in several cell types. Different cell lines and PBLs were transduced by retroviral vectors producing antisense RNA and were then challenged by HIV infection. We have shown that the endogenously expressed antisense RNA containing the natural open reading frame inhibits HIV-1(IIIB) and HIV-1(NDK) replication in these cells. The level of inhibition varied according to the cells, but was significant in all cases. The production of HIV-1 (BRU, IIIB, NDK) mRNAs was also significantly decreased. HIV-2 replication was not inhibited by expression of the antisense RNA. Our results also suggest that this inhibitory effect is due to the antisense RNA and not to the protein which is encoded by this sequence.
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PMID:Expression of naturally occurring antisense RNA inhibits human immunodeficiency virus type 1 heterologous strain replication. 934 71

Transmembrane glycoproteins with type 1 topology can be retrieved to the endoplasmic reticulum (ER) by a retrieval signal containing a di-lysine (KK) motif near the C terminus. To investigate the structural requirements for ER retrieval, we have constructed mutants of the simian immunodeficiency virus (SIV) envelope (Env) protein with cytoplasmic tails of different lengths and containing a KK motif at the -3 and -4 positions. Such proteins were found to be retained intracellularly when the signal was located 18 amino acids or more away from the membrane spanning domain. The retrieval signal was found to be functional even when placed at the distal end of the wild-type SIV Env protein with 164 amino acids in the cytoplasmic tail, as shown by the lack of proteolytic processing and lack of cell surface expression of the mutant proteins. However, proteins with a cytoplasmic tail length of 13 amino acids or less having the di-lysine motif at the -3 and -4 positions were not retrieved to the ER since they were found to be processed and transported to the cell surface. The surface-expressed proteins were found to be functional in inducing cell fusion, whereas the proteins retained intracellularly were defective in fusion activity. We also found that the KK motif introduced near an amphipathic helical region in the cytoplasmic tail was not functional. These results demonstrate that the ability of the KK motif to cause protein retrieval and retention in the endoplasmic reticulum depends on the length and structure of the cytoplasmic domain. The ER retrieval of the mutant proteins was found to correlate with increased intracellular binding to beta COP proteins.
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PMID:Function of the KKXX motif in endoplasmic reticulum retrieval of a transmembrane protein depends on the length and structure of the cytoplasmic domain. 942 55

We have previously reported on the generation of specific functional immune responses after inoculation of animals with expression vectors encoding HIV-1 genes. This article provides the details of the first application of this new technology to induce immune responses against HIV-2. This virus is molecularly and serologically distinct from HIV-1 and is in fact more closely related to the simian immunodeficiency virus (SIV). Anti-HIV-2 and SIV antibodies were induced in mice of three different haplotypes following a single intramuscular inoculation with an HIV-2/ROD envelope glycoprotein expression vector (pcEnv-2). Boosting of animals with pcEnv-2 induced both anti-HIV-2 neutralizing antibodies and T cell-proliferative responses against HIV-2 and SIVmac proteins. We compared the humoral and cellular immune responses of mice injected with pcEnv-2 and then boosted with either the homologous DNA construct or a recombinant Env protein. Animals boosted with pcEnv-2 generated B and T cell immune responses as strong as those of mice boosted with recombinant gp140 protein in adjuvant. Finally, cellular immune responses were significantly increased with the coadministration of pcEnv-2 and a plasmid expressing interleukin 12. We therefore conclude that DNA plasmid inoculation induces cross-reactive anti-HIV-2 and anti-SIVmac immune responses in mice. This technology should be further investigated as a potential vaccine component for this human pathogen.
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PMID:An HIV type 2 DNA vaccine induces cross-reactive immune responses against HIV type 2 and SIV. 943 Feb 48

Deletion of the simian immunodeficiency virus (SIV) nef gene leads to an attenuated virus phenotype in vivo. We have previously shown that these viruses induce a potent cellular immune response in macaques. To extend these studies, we established virus-specific short-term T-cell lines from four rhesus macaques infected with a nef deletion mutant of SIV. These T-cell lines proliferated upon restimulation with whole SIV or SIV gp140 antigen in vitro. The proliferating cells were characterized as CD4+ helper T-cells (TH) and their antigen recognition was MHC class II DR-restricted. After antigenic stimulation, they transcribed mRNA for various TH1- and TH2-like cytokines. Using these SIV-specific cell lines, a variety of helper T-cell epitopes in the SIV Env protein were determined with overlapping peptides. TH epitopes were identified throughout the whole SIV Env including both constant and variable regions. Although the recognition of TH epitopes was heterogeneous among different animals, five more broadly reactive T-cell epitopes were identified. As expected, recognition was associated with the MHC class II DRB background of the animals. This is the first report on helper T-cell epitopes in SIV-infected monkeys. Such studies should be of considerable significance for AIDS/ vaccine research.
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PMID:Specificity of helper T-cells generated from macaques infected with attenuated simian immunodeficiency virus. 968 Jan 45

The envelope (Env) proteins of primate lentiviruses interact sequentially with CD4 and a coreceptor to infect cells. Changes in coreceptor use strongly influence viral tropism and pathogenesis. We followed the evolution of coreceptor use in pig-tailed macaques that developed severe CD4 T-cell loss during the derivation of a pathogenic simian HIV (SHIV) that contained the tat, rev, vpu, and env genes of the HXBc2 strain of HIV-1 in a genetic background of SIVmac239. The Env from the parental virus as well as one derived from the first macaque to develop AIDS exclusively used CXCR4 as a coreceptor, indicating that CXCR4 can function as a coreceptor in macaques even though it is rarely used by simian immunodeficiency viruses. One Env (Pnb5), obtained from a macrophage-tropic virus isolated from the cerebral spinal fluid, did not use CCR5 or CXCR4. Instead, it used CCR2b and to a lesser extent CCR3, STRL33, and APJ to infect cells. Chimeras between Pnb5 and the parental X4 Env indicated that the V3 loop is the major determinant of CXCR4 use, with other regions of Env influencing the efficiency with which this coreceptor was used. In contrast, the Pnb5 V1/2 and V3 regions in combination were both necessary and sufficient to confer full use of CCR2b, CCR3, STRL33, and APJ to the parental X4 Env protein. These results are consistent with a single, conserved binding site in Env that interacts with multiple coreceptors in conjunction with the V1/2 and V3 loops, and suggest that the V1/2 region plays a more important role in governing the use of CCR2b, CCR3, STRL33, and APJ than for CXCR4.
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PMID:HIV type I envelope determinants for use of the CCR2b, CCR3, STRL33, and APJ coreceptors. 973 41

Previously we designed novel pseudotyped high-titer replication defective human immunodeficiency virus type 1 (HIV-1) vectors to deliver genes into nondividing cells (J. Reiser, G. Harmison, S. Kluepfel-Stahl, R. O. Brady, S. Karlsson, and M. Schubert, Proc. Natl. Acad. Sci. USA 93:15266-15271, 1996). Since then we have made several improvements with respect to the safety, flexibility, and efficiency of the vector system. A three-plasmid expression system is used to generate pseudotyped HIV-1 particles by transient transfection of human embryonic kidney 293T cells with a defective packaging construct, a plasmid coding for a heterologous envelope (Env) protein, and a vector construct harboring a reporter gene such as neo, ShlacZ (encoding a phleomycin resistance/beta-galactosidase fusion protein), HSA (encoding mouse heat-stable antigen), or EGFP (encoding enhanced green fluorescent protein). The packaging constructs lack functional Vif, Vpr, and Vpu proteins and/or a large portion of the Env coding region as well as the 5' and 3' long terminal repeats, the Nef function, and the presumed packaging signal. Using G418 selection, we routinely obtained vector particles pseudotyped with the vesicular stomatitis virus G glycoprotein (VSV-G) with titers of up to 8 x 10(7) CFU/microgram of p24, provided that a functional Tat coding region was present in the vector. Vector constructs lacking a functional Tat protein yielded titers of around 4 x 10(6) to 8 x 10(6) CFU/microgram of p24. Packaging constructs with a mutation within the integrase (IN) core domain profoundly affected colony formation and expression of the reporter genes, indicating that a functional IN protein is required for efficient transduction. We explored the abilities of other Env proteins to allow formation of pseudotyped HIV-1 particles. The rabies virus and Mokola virus G proteins yielded high-titer infectious pseudotypes, while the human foamy virus Env protein did not. Using the improved vector system, we successfully transduced contact-inhibited primary human skin fibroblasts and postmitotic rat cerebellar neurons and cardiac myocytes, a process not affected by the lack of the accessory proteins.
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PMID:High-titer human immunodeficiency virus type 1-based vector systems for gene delivery into nondividing cells. 976 32

DNA vaccination is an effective means of eliciting strong antibody responses to a number of viral antigens. However, DNA immunization alone has not generated persistent, high-titer antibody and neutralizing antibody responses to human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env). We have previously reported that DNA-primed anti-Env antibody responses can be augmented by boosting with Env-expressing recombinant vaccinia viruses. We report here that recombinant Env protein provides a more effective boost of DNA-initiated antibody responses. In rabbits primed with Env-expressing plasmids, protein boosting increased titer, persistence, neutralizing activity, and avidity of anti-Env responses. While titers increased rapidly after boosting, avidity and neutralizing activity matured more slowly over a 6-month period following protein boosting. DNA priming and protein immunization with HIV-1 HXB-2 Env elicited neutralizing antibody for T cell line-adapted, but not primary isolate, viruses. The most effective neutralizing antibody responses were observed after priming with plasmids which expressed noninfectious virus-like particles. In contrast to immunizations with HIV-1 Env, DNA immunizations with the influenza virus hemagglutinin glycoprotein did not require a protein boost to achieve high-titer antibody with good avidity and persistence.
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PMID:Studies of the neutralizing activity and avidity of anti-human immunodeficiency virus type 1 Env antibody elicited by DNA priming and protein boosting. 976 54

Human and simian immunodeficiency viruses (HIV and SIV, respectively) use chemokine receptors as coreceptors along with CD4 to mediate viral entry. Several orphan receptors, including GPR1, GPR15, and STRL33, can also serve as coreceptors for a more limited number of HIV and SIV isolates. We investigated whether these orphan receptors could function as efficient coreceptors for a diverse group of HIV and SIV envelopes (Envs) in comparison with the principal coreceptors CCR5 and CXCR4. We found that a limited number of HIV-1 isolates could mediate inefficient cell-cell fusion with the orphan receptors relative to CCR5 and CXCR4; however, none of the orphan receptors tested could support pseudotype virus infection despite robust infection via CCR5 or CXCR4. All except one of the SIV Envs tested mediated some degree of cell-cell fusion and pseudotype infection, with target cells expressing at least one of these orphan receptors, although CCR5 proved to be the most efficient coreceptor for infection. Only one SIV Env protein, BK28, could mediate infection using GPR1 as a coreceptor, albeit much less efficiently than with CCR5. In addition, use of these coreceptors did not correlate with the published tropism of the SIV clones and was strictly CD4 dependent for both SIV and HIV. We also examined the expression of these molecules in cell lines and primary cells widely used for virus propagation and as targets for infection. All cells examined expressed STRL33, a more limited number expressed GPR15, and GPR1 was much more restricted in its expression pattern. Taken together, our results indicate that GPR15 and STRL33 are rarely used by HIV-1 but are more frequently used by SIV strains, although not in a manner that correlates with SIV tropism.
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PMID:Use of GPR1, GPR15, and STRL33 as coreceptors by diverse human immunodeficiency virus type 1 and simian immunodeficiency virus envelope proteins. 979 Oct 28

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