UMLS:C0019693 - FACTA Search

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

Cell membrane protein (CMP) profile of HIV-1 from cerebrospinal fluid (CSF) and plasma of five AIDS patients with neurologic disorders was analyzed and compared with viral quasispecies composition in these body compartments. To this aim, paired CSF and plasma samples from AIDS subjects with HIV-related neurological diseases (three HIV-1 encephalopaty (HIVE) and two primary CNS lymphoma (PCNSL)) underwent immobilized antibody capture (IAC) assay to determine the profile of CMP acquired by HIV-1. The considered CMPs were CD45RO, CD26, CD36, glut-R, N-CAM, VCAM-1, ELAM-1, CD44 and CD58, representing lymphomonocyte, neuronal and adhesion molecules. Cloning and sequencing of env and gag regions was performed to predict coreceptor usage and to analyze quasispecies compartmentalization. The results indicated that CD44 and CD58 were the most represented molecules on HIV-1 from CSF, whereas CD36 was the most abundant molecule on plasma HIV-1. V3 env aminoacidic sequences and net charge were consistent with M-R5 phenotype in all CSF and in most plasma clones. The degree of genetic heterogeneity (both complexity and diversity) in p17 gag was significantly lower in CSF-HIV than that in plasma-HIV for three patients, higher for one patient, and not significantly different for one patient, suggesting compartmentalization for all but the latter patient. When considering the pattern of CMP, the most abundant CMP observed in HIV from plasma and CSF was different in patients showing compartmentalization, while was the same in the patient without significant differences in CSF and plasma quasispecies. In conclusion, the present data on CMP pattern, V3 loop aminoacidic signature and genetic heterogeneity of HIV-1 quasispecies from CSF and plasma of HIVE patients, are consistent with a compartmentalized virus replication, at least in some patients, and with a possible different source of HIV in the two body sites, even though in a context of a largely prevalent M-R5 phenotype.
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PMID:Cell membrane proteins and quasispecies compartmentalization of CSF and plasma HIV-1 from aids patients with neurological disorders. 1573 16

Human immunodeficiency virus type 1 (HIV-1) along with simian immunodeficiency viruses from chimpanzees (SIV(cpz)) and three species of Old World monkeys from the genus Cercopithecus have been shown to encode a Vpu protein. To date, the functional characterization of Vpu has been limited to a small number of subtype B and more recently subtype C Vpu proteins. Using a recently developed VpuEGFP reporter system, we have shown that the subtype B and C Vpus are capable of preventing CD4 from being expressed on the cell surface. Using the same reporter system, we report here on the expression and functional analysis of Vpu protein from four SIV(cpz) isolates (CAM13, ANT, TAN1, and GAB1). All four SIV Vpu fusion proteins were efficiently expressed and prevented CD4 expression on the cell surface and induced CD4 degradation. This was surprising as three of the SIV(cpz) Vpu fusion proteins had only one canonical casein kinase II (CK-II) site (CAM13, ANT, TAN1) while previous studies with laboratory adapted HXB2 had indicated that both CK-II sites were required for CD4 degradation. Both ANT and TAN1 Vpu sequences encoded five consecutive negatively charged amino acids residues following the only CKII site (SAIEEDEE for ANT; SGVEEDEE for TAN1). We thus explored the possibility that this stretch of negatively charged amino acids might substitute for the lack of second CK-II site. Substitution of the aspartic acid at position 61 and glutamic acid at position 63 in the SIV(cpz) ANT Vpu within with lysine residues abolished the ability of this protein to down-modulate cell surface expression of CD4. Similarly, change of a serine to an alanine residue following the single consensus CK-II site of the CAM13 Vpu (SGNESDGGEEE) abolished CD4-down-regulation, suggesting that this serine was phosphorylated in the absence of a canonical CK-II site. Our results indicate that the serine was required, suggesting that this serine was phosphorylated by CK-II or possibly another cellular kinase. Taken together, these results show for the first time that Vpu proteins from SIV(cpz) isolates, although quite diverse in sequence and predicted secondary structure from the HIV-1 subtype B protein, are capable of down-regulating CD4, which is one of the major functions of the HIV-1 protein.
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PMID:Vpu-mediated CD4 down-regulation and degradation is conserved among highly divergent SIV(cpz) strains. 1582 5

Recombination due to template switching during reverse transcription is a major source of genetic variability in retroviruses. In the present study we forced a recombination event in human immunodeficiency virus type 1 (HIV-1) by electroporation of T cells with DNA from a molecular HIV-1 clone that has a 300 bp long hairpin structure in the Nef gene (HIV-lhNef). HIV-lhNef does not replicate, but replication-competent escape variants emerged in four independent cultures. The major part of the hairpin was deleted in all escape viruses. In three cases, the hairpin deletion was linked to patch insertion of tRNA(asp), tRNA(glu) or tRNA(trp) sequences. The tRNAs were inserted in the viral genome in the antisense orientation, indicating that tRNA-mediated recombination occurred during minus-strand DNA synthesis. We here propose a mechanistic model for this hairpin-induced tRNA-mediated (HITME) recombination. The transient role of the cellular tRNA molecule as enhancer of retroviral recombination is illustrated by the eventual removal of inserted tRNA sequences by a subsequent recombination/deletion event.
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PMID:Hairpin-induced tRNA-mediated (HITME) recombination in HIV-1. 1667 Apr 29

Noncovalent interactions of the polyhedral carborane 1-carba-closo-dodecaborane (CB(11)H(12))(-) with building blocks of biomolecules, modelled by glycine (GLY), serine (SER), phenylalanine (PHE), glutamic acid (GLU), lysine (LYS) and arginine (ARG), were investigated in vacuo by molecular dynamics simulations with the UFF empirical potential. Selected structures were further studied by accurate ab initio quantum chemical procedures. Interactions with a peptide bond (GLY-SER dipeptide) and a nucleic acid building block (guanine) were also considered. The RESP and NPA charges of carboranes and small model systems are compared and their use is discussed. The dominant interaction between carboranes and biomolecules is the formation of unconventional proton-hydride hydrogen bonds (dihydrogen bonds) characterized by a short distance between hydrogen atoms (as close as 1.8 A) and an average strength in the range of 4.2-5.8 kcal mol(-1). The total stabilization energy of complexes investigated is rather large, and the largest value (approximately 15 kcal mol(-1)) was found for the carborane complexes with ARG and the GLY-SER dipeptide. These interactions are ubiquitous under geometrical constraints influencing the strength of the interaction. The carborane forms dihydrogen bonds with biomolecules preferably with the hydrogen atoms of its lower hemisphere (i.e. the part of the cage opposite to the carbon atom). These two geometrical factors can be used to explain the specificity of inhibition of HIV protease by carboranes.
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PMID:Interaction of carboranes with biomolecules: formation of dihydrogen bonds. 1667 Nov 16

The human immunodeficiency virus type 1 (HIV-1) Gag protein recruits Tsg101 to facilitate HIV-1 particle budding and release. In uninfected cells, the Hrs protein recruits the ESCRT-I complex to the endosome, also through an interaction with Tsg101, to promote the sorting of host proteins into endosomal vesicles and multivesicular bodies. Here, we show that the overexpression of the C-terminal fragment of Hrs (residues 391 to 777) or Hrs mutants lacking either the N-terminal FYVE domain (mutant dFYVE) or the PSAP (residues 348 to 351) motif (mutant ASAA) all efficiently inhibit HIV-1 Gag particle production. Expression of the dFYVE or ASAA mutants of Hrs had no effect on the release of Moloney murine leukemia virus. Coimmunoprecipitation analysis showed that the expression of Hrs mutant dFYVE or ASAA significantly reduced or abolished the HIV-1 Gag-Tsg101 interaction. Yeast-two hybrid assays were used to identify two new and independent Tsg101 binding sites, one in the Hrs coiled-coil domain and one in the proline/glutamic acid-rich domain. Scanning electron microscopy of HeLa cells expressing HIV-1 Gag and the Hrs ASAA mutant showed viral particles arrested in "lump-like" structures that remained attached to the cell surface. Together, these data indicate that fragments of Hrs containing the C-terminal portion of the protein can potently inhibit HIV-1 particle release by efficiently sequestering Tsg101 away from the Gag polyprotein.
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PMID:The C-terminal portion of the Hrs protein interacts with Tsg101 and interferes with human immunodeficiency virus type 1 Gag particle production. 1718 74

The development of a prophylactic/therapeutic HIV-1 vaccine based on recombinant proteins is needed for the control of the worldwide AIDS epidemic. Subunit protein and peptide vaccines are generally very safe, with well-defined components. However, these antigens are often poorly immunogenic, and thus require the use of adjuvants to induce adequate immunity. Particulate adjuvants (e.g. micro/nanoparticles, emulsions, ISCOMS, liposomes, virosomes, and virus-like particles) have been widely investigated as HIV-1 vaccine delivery systems. Antigen uptake by antigen-presenting cells (APC) is enhanced by the association of the antigens with polymeric micro/nanoparticles. The adjuvant effect of micro/nanoparticles appears to largely be a consequence of their uptake into APC. More importantly, particulate antigens have been shown to be more efficient than soluble antigens for the induction of immune responses. Over the past two decades, we have studied the synthesis and clinical applications of core-corona polymeric nanospheres composed of hydrophobic polystyrene and hydrophilic macromonomers. Core-corona type polymeric nanospheres have applications in various technological and biomedical fields, because their chemical structures and particle size can be easily controlled. In this study, we focused on the development of a HIV-1 vaccine using polymeric nanoparticles. We evaluated the immunization strategies for HIV-1-capturing core-corona type polystyrene nanospheres that would efficiently induce HIV-1-specific IgA responses in female mice and the macaque genital tract. Moreover, based on this research, we attempted to develop novel biodegradable nanoparticles composed of poly (gamma-glutamic acid) (gamma-PGA) for protein-based vaccine delivery. These HIV-1-capturing nanospheres and protein-loaded gamma-PGA nanoparticles have shown unique potential as vaccine carriers.
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PMID:[Development of vaccine adjuvants using polymeric nanoparticles and their potential applications for anti-HIV vaccine]. 1726 51

An essential step in the replication of all retroviruses is the capture of a cellular tRNA that is used as the primer for reverse transcription. The 3'-terminal 18 nucleotides of the tRNA are complementary to the primer binding site (PBS). Moloney murine leukemia virus (MuLV) preferentially captures tRNA(Pro). To investigate the specificity of primer selection, the PBS of MuLV was altered to be complementary to different tRNAs. Analysis of the infectivity of the virus and stability of the PBS following in vitro replication revealed that MuLV prefers to select tRNA(Pro), tRNA(Gly), or tRNA(Arg). Previous studies from our laboratory have suggested that tRNA primer capture is coordinated with translation. Coincidentally, a cluster of proline, arginine, and glycine precedes the Gag-Pol junction of MuLV. Human immunodeficiency virus type 1 (HIV-1), which prefers tRNA(3)(Lys) as the primer, can be forced to utilize tRNA(Met), tRNA(1,2)(Lys), tRNA(His), or tRNA(Glu), although these viruses replicate poorly. Codons for methionine, lysine, histidine, or glutamic acid are found prior to the Gag-Pol frameshift site. HIV-1 was mutated so that the 5 lysine codons prior to the Gag-Pol frameshift region were specific for tRNA(1,2)(Lys). HIV-1 forced to use tRNA(1,2)(Lys) as the primer, with the mutation of codons specific for tRNA(1,2)(Lys) prior to the Gag-Pol junction, had enhanced infectivity and replicated similarly to the wild-type virus. The results demonstrate that codon preference prior to the Gag-Pol junction influences primer selection and suggest a coordination of Gag-Pol synthesis and acquisition of the tRNA primer required for retrovirus replication.
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PMID:tRNA isoacceptor preference prior to retrovirus Gag-Pol junction links primer selection and viral translation. 1730 Nov 32

The mainstream of recent anti-AIDS vaccines is a prime/boost approach with multiple doses of the target DNA of human immunodeficiency virus type 1 (HIV-1) and recombinant viral vectors. In this study, we have attempted to construct an efficient protein-based vaccine using biodegradable poly(gamma-glutamic acid) (gamma-PGA) nanoparticles (NPs), which are capable of inducing potent cellular immunity. A significant expansion of CD8+ T cells specific to the major histocompatibility complex class I-restricted gp120 epitope was observed in mice intranasally immunized once with gp120-carrying NPs but not with gp120 alone or gp120 together with the B-subunit of cholera toxin. Both the gp120-encapsulating and -immobilizing forms of NPs could induce antigen-specific spleen CD8+ T cells having a functional profile of cytotoxic T lymphocytes. Long-lived memory CD8+ T cells could also be elicited. Although a substantial decay in the effector memory T cells was observed over time in the immunized mice, the central memory T cells remained relatively constant from day 30 to day 238 after immunization. Furthermore, the memory CD8+ T cells rapidly expanded with boosting with the same immunogen. In addition, gamma-PGA NPs were found to be a much stronger inducer of antigen-specific CD8+ T-cell responses than nonbiodegradable polystyrene NPs. Thus, gamma-PGA NPs carrying various HIV-1 antigens may have great potential as a novel priming and/or boosting tool in current vaccination regimens for the induction of cellular immune responses.
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PMID:Induction of potent CD8+ T-cell responses by novel biodegradable nanoparticles carrying human immunodeficiency virus type 1 gp120. 1760 61

Antigen delivery systems using polymeric nanoparticles are of special interest as stable protein-based antigen carriers. In the present study, novel biodegradable poly(gamma-glutamic acid) (gamma-PGA) nanoparticles were examined for their antigen delivery and immunostimulatory activities in vitro and in vivo. The uptake of ovalbumin by dendritic cells was markedly enhanced by gamma-PGA nanoparticles, and the ovalbumin was gradually released from gamma-PGA nanoparticles into the cells. In addition, gamma-PGA nanoparticles appeared to have great potential as an adjuvant, because they could induce the maturation of dendritic cells. Although not only ovalbumin-encapsulating nanoparticles (OVA-NPs) but also a simple mixture of ovalbumin and nanoparticles induced dendritic cell maturation, the only dendritic cells exposed to OVA-NPs could strongly activate antigen-specific interferon (IFN)-gamma-producing T cells. Subcutaneous immunization of mice with human immunodeficiency virus type 1 (HIV-1) p24-encapsulating nanoparticles activated antigen-specific IFN-gamma-producing T cells in spleen cells and induced p24-specific serum antibodies, as compared to immunization with p24 alone. Like ovalbumin, a mixture of p24 and nanoparticles also induced antigen-specific serum antibodies but did not activate IFN-gamma-producing T cells in spleen cells, suggesting that nanoparticles play a critical role in inducing cellular immune responses. Furthermore, gamma-PGA nanoparticles had a capacity comparable to that of the complete Freund's adjuvant (CFA) in inducing p24-specific serum antibody. However, unlike CFA, they predominantly activated p24-specific IFN-gamma-producing T cells. Thus, gamma-PGA nanoparticles encapsulating various antigens may have great potential as novel and efficient protein-based vaccines against infectious diseases, including HIV-1 infection.
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PMID:Poly(gamma-glutamic acid) nanoparticles as an efficient antigen delivery and adjuvant system: potential for an AIDS vaccine. 1804 Oct 33

This study reported the prevalence and pattern of viral replication-associated HIV-1 protease codon 35 amino acid insertions among treatment-naive patients in Hong Kong. The transmission and divergence date of these inserted strains was also investigated. The pol gene of 264 local HIV-1 isolates was sequenced and phylogenetic analysis was performed. The transmission history of protease codon 35-inserted HIV-1 strains in Hong Kong was estimated by the Bayesian coalescent method. This insertion was detected in 12 (4.55%) among 264 treatment-naive subtype B HIV-1 patients in Hong Kong, which was 20-times higher than the prevalence in the western countries. Among these strains, eight carried a glutamic acid (GAA) insertion (E35E_E), two carried an aspartic acid (GAC) insertion (E35E_D), and two carried a glycine (GGA) insertion (E35E_G). E35E_D and E35E_E insertions were the first to be reported. All the 12 inserted sequences clustered in the same lineage of the phylogenetic tree, indicating the possibility of transmission of this insertion. Epidemiological investigation revealed the major route of infection for this inserted strain in Hong Kong was associated mainly among homosexual Chinese males. The evolutionary rate of these inserted strains was similar to other subtype B HIV-1 strains. Through coalescent-based analysis, the divergence date of the protease codon 35-inserted strains in Hong Kong was 1995. Our findings demonstrate the epidemic pathways of viral fitness-related HIV-1 protease codon 35-inserted isolates in Hong Kong. The effect of these novel insertions on viral fitness and drug susceptibility requires further investigation.
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PMID:Molecular epidemiology and divergence of HIV type 1 protease codon 35 inserted strains among treatment-naive patients in Hong Kong. 1842 35

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