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1

Candidate Sulfonated and Sulfated Topical Microbicides: Comparison of Anti-Human Immunodeficiency Virus Activities and Mechanisms of Action  

Microsoft Academic Search

Poly(styrene 4-sulfonate), cellulose sulfate, polymethylenehydroquinone, and PRO 2000 are sulfated or sulfonated polymers (SPs) under development as topical microbicides. They are presumed to work through similar mechanisms of action, although to date there has been no extensive comparison of their anti-human immunodeficiency virus activities. To determine whether any of these candidate microbicides offers a potential advantage, their in vitro activities,

Irini A. Scordi-Bello; Arevik Mosoian; Cejiang He; Yiban Chen; Yang Cheng; Gary A. Jarvis; Marla J. Keller; Kathleen Hogarty; Donald P. Waller; Albert T. Profy; Betsy C. Herold; Mary E. Klotman

2005-01-01

2

Feline Immunodeficiency Virus (FIV) Neutralization: A Review  

PubMed Central

One of the major obstacles that must be overcome in the design of effective lentiviral vaccines is the ability of lentiviruses to evolve in order to escape from neutralizing antibodies. The primary target for neutralizing antibodies is the highly variable viral envelope glycoprotein (Env), a glycoprotein that is essential for viral entry and comprises both variable and conserved regions. As a result of the complex trimeric nature of Env, there is steric hindrance of conserved epitopes required for receptor binding so that these are not accessible to antibodies. Instead, the humoral response is targeted towards decoy immunodominant epitopes on variable domains such as the third hypervariable loop (V3) of Env. For feline immunodeficiency virus (FIV), as well as the related human immunodeficiency virus-1 (HIV-1), little is known about the factors that lead to the development of broadly neutralizing antibodies. In cats infected with FIV and patients infected with HIV-1, only rarely are plasma samples found that contain antibodies capable of neutralizing isolates from other clades. In this review we examine the neutralizing response to FIV, comparing and contrasting with the response to HIV. We ask whether broadly neutralizing antibodies are induced by FIV infection and discuss the comparative value of studies of neutralizing antibodies in FIV infection for the development of more effective vaccine strategies against lentiviral infections in general, including HIV-1. PMID:22069520

Hosie, Margaret J.; Pajek, Daniela; Samman, Ayman; Willett, Brian J.

2011-01-01

3

Sophorolipids, microbial glycolipids with anti-human immunodeficiency virus and sperm-immobilizing activities.  

PubMed

The increased incidence of human immunodeficiency virus (HIV)/AIDS disease in women aged 15 to 49 years has identified the urgent need for a female-controlled, efficacious, and safe vaginal topical microbicide. To meet this challenge, sophorolipid (SL) produced by Candida bombicola and its structural analogs have been studied in this report for their spermicidal, anti-HIV, and cytotoxic activities. The sophorolipid diacetate ethyl ester derivative is the most potent spermicidal and virucidal agent of the series of SLs studied. Its virucidal activity against HIV and sperm-immobilizing activity against human semen are similar to those of nonoxynol-9. However, it also induced enough vaginal cell toxicity to raise concerns about its applicability for long-term microbicidal contraception. Its structure-activity relationship has been established for creating new analogs with less cytotoxicity and higher activity. PMID:16189085

Shah, Vishal; Doncel, Gustavo F; Seyoum, Theodoros; Eaton, Kristin M; Zalenskaya, Irina; Hagver, Rena; Azim, Abul; Gross, Richard

2005-10-01

4

Sophorolipids, Microbial Glycolipids with Anti-Human Immunodeficiency Virus and Sperm-Immobilizing Activities  

PubMed Central

The increased incidence of human immunodeficiency virus (HIV)/AIDS disease in women aged 15 to 49 years has identified the urgent need for a female-controlled, efficacious, and safe vaginal topical microbicide. To meet this challenge, sophorolipid (SL) produced by Candida bombicola and its structural analogs have been studied in this report for their spermicidal, anti-HIV, and cytotoxic activities. The sophorolipid diacetate ethyl ester derivative is the most potent spermicidal and virucidal agent of the series of SLs studied. Its virucidal activity against HIV and sperm-immobilizing activity against human semen are similar to those of nonoxynol-9. However, it also induced enough vaginal cell toxicity to raise concerns about its applicability for long-term microbicidal contraception. Its structure-activity relationship has been established for creating new analogs with less cytotoxicity and higher activity. PMID:16189085

Shah, Vishal; Doncel, Gustavo F.; Seyoum, Theodoros; Eaton, Kristin M.; Zalenskaya, Irina; Hagver, Rena; Azim, Abul; Gross, Richard

2005-01-01

5

Preclinical safety assessments of UC781 anti-human immunodeficiency virus topical microbicide formulations.  

PubMed

The nonnucleoside reverse transcriptase inhibitor UC781 is under development as a potential microbicide to prevent sexual transmission of human immunodeficiency virus type 1 (HIV-1). Two gel formulations of UC781 (0.1% and 1.0%) were evaluated in a range of preclinical safety assessments, including systemic absorption analysis following topical application in the pig-tailed macaque models for vaginally and rectally applied topical microbicides. High-sensitivity high-performance liquid chromatography analysis of serum samples showed that no systemic absorption of UC781 was detected after repeated vaginal or rectal application of either product. However, high levels of UC781 were detectable in the cervicovaginal lavage samples up to 6 h after product exposure. Both formulations were safe to the vaginal microenvironment, even with repeated daily use, as evidenced by colposcopy, cytokine analysis, and lack of impact on vaginal microflora. By contrast, rectal application of the 1.0% UC781 formulation caused an increased expression of numerous cytokines not observed after rectal application of the 0.1% UC781 formulation. These results provide additional support for the continued development of UC781 formulations as anti-HIV microbicides. PMID:17353240

Patton, D L; Sweeney, Y T Cosgrove; Balkus, J E; Rohan, L C; Moncla, B J; Parniak, M A; Hillier, S L

2007-05-01

6

Essential regions for antiviral activities of actinohivin, a sugar-binding anti-human immunodeficiency virus protein from an actinomycete.  

PubMed

Actinohivin (AH) is a potent anti-human immunodeficiency virus (HIV) protein that consists of highly conserved three-tandem repeats (segments 1, 2, and 3). The molecular target of AH in its anti-HIV activity is high-mannose-type saccharide chains of HIV gp120. This article deals with sequence requirements for the anti-HIV activity of AH. The deleted or substituted DNAs encoding AH or His-AH were prepared using mutagenic oligonucleotide primers in PCR. The mutant constructs were expressed in Escherichia coli, and the activities of the recombinant protein products were examined by a syncytium-formation assay system that mimics anti-HIV activity. The single segment mutant His-AHs showed no anti-syncytium-formation activity, but the mutant His-AHs, which consists of 2 or 3 segments, retained reduced activities. His-AH(6-114) dramatically reduced the anti-syncytium-formation activity to that of His-AH(36-114) or His-AH(I5A). Furthermore, His-AH(Q33A), His-AH(Q71A), and His-AH(Q109A) in which glutamine residues were substituted into alanine showed reduced activities of 1/20, 1/10, and 1/30, respectively, in anti-syncytium formation compared with His-AH. These results indicate that three segments of AH are necessary for potent anti-syncytium-formation activity-that is, for potent anti-HIV activity and the cooperated involvement of each segment of AH increased the AH-gp120 interaction. PMID:15850563

Takahashi, Atsushi; Inokoshi, Junji; Chiba, Harumi; Omura, Satoshi; Tanaka, Haruo

2005-05-15

7

Immunodeficiency  

Microsoft Academic Search

Traditionally immunodeficiency is attributed to internal structural and\\/or regulatory defects ofthe immune system, although it is recognized that some of the deficiencies are complex. Animal experiments and some observations in man clearly indicate that abnormalities of the neuroendocrine system are also able to cause immunodeficiency.Hypophysectomized (Hypox) rats are immunodeficient. If the residual serum PRL present in Hypox animals is neutralized,

Istvan Berczi; Andor Szentivanyi

2003-01-01

8

Anti-human immunodeficiency virus synergism by zidovudine (3'-azidothymidine) and didanosine (dideoxyinosine) contrasts with their additive inhibition of normal human marrow progenitor cells.  

PubMed Central

The anti-human immunodeficiency virus (HIV) activity and hemopoietic toxicity of zidovudine (AZT) and didanosine (dideoxyinosine;ddI), alone and in combination, were assessed in a variety of cell types. AZT was more potent than ddI as an inhibitor of HIV in vitro. Synergistic inhibition of HIV by the combination of these agents was observed in MT4 cells, peripheral blood lymphocytes, and macrophages. Toxicity assessment in vitro by using progenitor (erythroid and granulocyte-macrophage) colony-forming assays with normal human bone marrow showed ddI to be less toxic than AZT. Addition of inhibitory concentrations of ddI to AZT resulted in additive inhibition of progenitor CFUs. These in vitro findings suggest that combinations of ddI and AZT at appropriately modified doses may provide an enhanced degree of selectivity in anti-HIV chemotherapy. PMID:1708977

Dornsife, R E; St Clair, M H; Huang, A T; Panella, T J; Koszalka, G W; Burns, C L; Averett, D R

1991-01-01

9

Mechanism of Anti-Human Immunodeficiency Virus Activity of  -D-6-Cyclopropylamino-2',3'-Didehydro-2',3'-Dideoxyguanosine  

Microsoft Academic Search

To better understand the importance of the oxygen in the ribose ring of planar unsaturated nucleoside analogs that target human immunodeficiency virus (HIV), a 6-cyclopropyl-substituted prodrug of 2,3-dide- hydro-2,3-dideoxyguanosine (cyclo-d4G) was synthesized, and its cellular metabolism, antiviral activity, and pharmacokinetic behavior were studied. Cyclo-d4G had selective anti-HIV activity in primary blood mononu- clear cells (PBMCs), effectively inhibiting the LAI strain

Adrian S. Ray; Brenda I. Hernandez-Santiago; Judy S. Mathew; Eisuke Murakami; Carey Bozeman; Meng-Yu Xie; Ginger E. Dutschman; Elizabeth Gullen; Zhenjun Yang; Selwyn Hurwitz; Yung-Chi Cheng; Chung K. Chu; Harold McClure; Raymond F. Schinazi; Karen S. Anderson

2005-01-01

10

Cellular Immunity Elicited by Human Immunodeficiency Virus Type 1/ Simian Immunodeficiency Virus DNA Vaccination Does Not Augment the Sterile Protection Afforded by Passive Infusion of Neutralizing Antibodies  

PubMed Central

High levels of infused anti-human immunodeficiency virus type 1 (HIV-1) neutralizing monoclonal antibodies (MAbs) can completely protect macaque monkeys against mucosal chimeric simian-human immunodeficiency virus (SHIV) infection. Antibody levels below the protective threshold do not prevent infection but can substantially reduce plasma viremia. To assess if HIV-1/SIV-specific cellular immunity could combine with antibodies to produce sterile protection, we studied the effect of a suboptimal infusion of anti-HIV-1 neutralizing antibodies in macaques with active cellular immunity induced by interleukin-2 (IL-2)-adjuvanted DNA immunization. Twenty female macaques were divided into four groups: (i) DNA immunization plus irrelevant antibody, (ii) DNA immunization plus infusion of neutralizing MAbs 2F5 and 2G12, (iii) sham DNA plus 2F5 and 2G12, and (iv) sham DNA plus irrelevant antibody. DNA-immunized monkeys developed CD4 and CD8 T-cell responses as measured by epitope-specific tetramer staining and by pooled peptide ELISPOT assays for gamma interferon-secreting cells. After vaginal challenge, DNA-immunized animals that received irrelevant antibody became SHIV infected but displayed lower plasma viremia than control animals. Complete protection against SHIV challenge occurred in three animals that received sham DNA plus MAbs 2F5 and 2G12 and in two animals that received the DNA vaccine plus MAbs 2F5 and 2G12. Thus, although DNA immunization produced robust HIV-specific T-cell responses, we were unable to demonstrate that these responses contributed to the sterile protection mediated by passive infusion of neutralizing antibodies. These data suggest that although effector T cells can limit viral replication, they are not able to assist humoral immunity to prevent the establishment of initial infection. PMID:12970419

Mascola, John R.; Lewis, Mark G.; VanCott, Thomas C.; Stiegler, Gabriela; Katinger, Hermann; Seaman, Michael; Beaudry, Kristin; Barouch, Dan H.; Korioth-Schmitz, Birgit; Krivulka, Georgia; Sambor, Anna; Welcher, Brent; Douek, Daniel C.; Montefiori, David C.; Shiver, John W.; Poignard, Pascal; Burton, Dennis R.; Letvin, Norman L.

2003-01-01

11

Antibody Specificities Associated with Neutralization Breadth in Plasma from Human Immunodeficiency Virus Type 1 Subtype C-Infected Blood Donors? †  

PubMed Central

Defining the specificities of the anti-human immunodeficiency virus type 1 (HIV-1) envelope antibodies able to mediate broad heterologous neutralization will assist in identifying targets for an HIV-1 vaccine. We screened 70 plasmas from chronically HIV-1-infected individuals for neutralization breadth. Of these, 16 (23%) were found to neutralize 80% or more of the viruses tested. Anti-CD4 binding site (CD4bs) antibodies were found in almost all plasmas independent of their neutralization breadth, but they mainly mediated neutralization of the laboratory strain HxB2 with little effect on the primary virus, Du151. Adsorption with Du151 monomeric gp120 reduced neutralizing activity to some extent in most plasma samples when tested against the matched virus, although these antibodies did not always confer cross-neutralization. For one plasma, this activity was mapped to a site overlapping the CD4-induced (CD4i) epitope and CD4bs. Anti-membrane-proximal external region (MPER) (r = 0.69; P < 0.001) and anti-CD4i (r = 0.49; P < 0.001) antibody titers were found to be correlated with the neutralization breadth. These anti-MPER antibodies were not 4E10- or 2F5-like but spanned the 4E10 epitope. Furthermore, we found that anti-cardiolipin antibodies were correlated with the neutralization breadth (r = 0.67; P < 0.001) and anti-MPER antibodies (r = 0.6; P < 0.001). Our study suggests that more than one epitope on the envelope glycoprotein is involved in the cross-reactive neutralization elicited during natural HIV-1 infection, many of which are yet to be determined, and that polyreactive antibodies are possibly involved in this phenomenon. PMID:19553335

Gray, Elin S.; Taylor, Natasha; Wycuff, Diane; Moore, Penny L.; Tomaras, Georgia D.; Wibmer, Constantinos Kurt; Puren, Adrian; DeCamp, Allan; Gilbert, Peter B.; Wood, Blake; Montefiori, David C.; Binley, James M.; Shaw, George M.; Haynes, Barton F.; Mascola, John R.; Morris, Lynn

2009-01-01

12

Cytochrome P450 3A5 plays a prominent role in the oxidative metabolism of the anti-human immunodeficiency virus drug maraviroc.  

PubMed

Maraviroc is an anti-human immunodeficiency virus drug that acts by blocking viral entry into target cells. With use of ultra-performance liquid chromatography-mass spectrometry several monooxygenated, dioxygenated, and glucuronidated metabolites of maraviroc were identified both in vitro and in vivo. Characterization of the enzymes involved in the production of these metabolites determined that cytochrome P450 3A5 was the principal enzyme responsible for the formation of an abundant metabolite of maraviroc that resulted from oxygenation of the dichlorocyclohexane ring. For the formation of this metabolite, the V(max) values for CYP3A4 and CYP3A5 were 0.04 and 0.93 pmol · min?¹ · pmol P450?¹, and the K(m) values were 11.1 and 48.9 ?M, respectively. Furthermore, human liver microsomes isolated from donors homozygous for the loss-of-function CYP3A5*3 allele exhibited a 79% decrease in formation of this metabolite compared with those homozygous for the wild-type CYP3A5*1 allele. To probe which divergent residues between CYP3A4 and CYP3A5 might play a role in the differential activities of these enzymes toward maraviroc, mutations were introduced into both enzymes and metabolism of maraviroc was measured. A CYP3A5 L57F mutant exhibited a 61% decrease in the formation of this metabolite, whereas formation by a CYP3A4 F57L mutant was increased by 337% compared with that of the wild type. Taken together, these data provide novel insights into the biotransformation of maraviroc as well as the potential role of CYP3A4 and CYP3A5 divergent residues in the enzymatic activities of these two highly homologous enzymes. PMID:22923690

Lu, Yanhui; Hendrix, Craig W; Bumpus, Namandjé N

2012-12-01

13

Cytochrome P450 3A5 Plays a Prominent Role in the Oxidative Metabolism of the Anti-Human Immunodeficiency Virus Drug Maraviroc  

PubMed Central

Maraviroc is an anti-human immunodeficiency virus drug that acts by blocking viral entry into target cells. With use of ultra-performance liquid chromatography-mass spectrometry several monooxygenated, dioxygenated, and glucuronidated metabolites of maraviroc were identified both in vitro and in vivo. Characterization of the enzymes involved in the production of these metabolites determined that cytochrome P450 3A5 was the principal enzyme responsible for the formation of an abundant metabolite of maraviroc that resulted from oxygenation of the dichlorocyclohexane ring. For the formation of this metabolite, the Vmax values for CYP3A4 and CYP3A5 were 0.04 and 0.93 pmol · min?1 · pmol P450?1, and the Km values were 11.1 and 48.9 ?M, respectively. Furthermore, human liver microsomes isolated from donors homozygous for the loss-of-function CYP3A5*3 allele exhibited a 79% decrease in formation of this metabolite compared with those homozygous for the wild-type CYP3A5*1 allele. To probe which divergent residues between CYP3A4 and CYP3A5 might play a role in the differential activities of these enzymes toward maraviroc, mutations were introduced into both enzymes and metabolism of maraviroc was measured. A CYP3A5 L57F mutant exhibited a 61% decrease in the formation of this metabolite, whereas formation by a CYP3A4 F57L mutant was increased by 337% compared with that of the wild type. Taken together, these data provide novel insights into the biotransformation of maraviroc as well as the potential role of CYP3A4 and CYP3A5 divergent residues in the enzymatic activities of these two highly homologous enzymes. PMID:22923690

Lu, Yanhui; Hendrix, Craig W.

2012-01-01

14

Biocompatibility of solid-dosage forms of anti-human immunodeficiency virus type 1 microbicides with the human cervicovaginal mucosa modeled ex vivo.  

PubMed

Topical anti-human immunodeficiency virus (HIV) microbicides are being sought to reduce the spread of HIV type 1 (HIV-1) during sexual intercourse. The success of this strategy depends upon the selection of formulations compatible with the natural vaginal mucosal barrier. This study applied ex vivo-modeled human cervicovaginal epithelium to evaluate experimental solid-dosage forms of the anti-HIV-1 microbicide cellulose acetate 1,2-benzenedicarboxylate (CAP) and over-the-counter (OTC) vaginal products for their impact on inflammatory mediators regarded as potential HIV-1-enhancing risk factors. We assessed product-induced imbalances between interleukin-1alpha (IL-1alpha) and IL-1beta and the natural IL-1 receptor antagonist (IL-1RA) and changes in levels of IL-6, tumor necrosis factor alpha, IL-8, gamma interferon inducible protein 10 (IP-10), and macrophage inflammatory protein 3alpha (MIP-3alpha), known to recruit and activate monocytes, dendritic cells, and T cells to the inflamed mucosa. CAP film and gel formulation, similarly to the hydroxyethylcellulose universal vaginal placebo gel and the OTC K-Y moisturizing gel, were nontoxic and caused no significant changes in any inflammatory biomarker. In contrast, OTC vaginal cleansing and contraceptive films containing octoxynol-9 or nonoxynol-9 (N-9) demonstrated similar levels of toxicity but distinct immunoinflammatory profiles. IL-1alpha, IL-1beta, IL-8, and IP-10 were increased after treatment with both OTC vaginal cleansing and contraceptive films; however, MIP-3alpha was significantly elevated by the N-9-based film only (P < 0.01). Although both films increased extracellular IL-1RA, the cleansing film only significantly elevated the IL-1RA/IL-1 ratio (P < 0.001). The N-9-based film decreased intracellular IL-1RA (P < 0.05), which has anti-inflammatory intracrine functions. This study identifies immunoinflammatory biomarkers that can discriminate between formulations better than toxicity assays and should be clinically validated in relevance to the risk of HIV-1 acquisition. PMID:17030562

Trifonova, Radiana T; Pasicznyk, Jenna-Malia; Fichorova, Raina N

2006-12-01

15

Kinetic Rates of Antibody Binding Correlate with Neutralization Sensitivity of Variant Simian Immunodeficiency Virus Strains  

Microsoft Academic Search

Increasing evidence suggests that an effective AIDS vaccine will need to elicit both broadly reactive humoral and cellular immune responses. Potent and cross-reactive neutralization of simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) by polyclonal and monoclonal antibodies is well documented. However, the mechanisms of antibody-mediated neutralization have not been defined. The current study was designed to

Jonathan D. Steckbeck; Irina Orlov; Andrew Chow; Heather Grieser; Kenneth Miller; JoAnne Bruno; James E. Robinson; Ronald C. Montelaro; Kelly Stefano Cole

2005-01-01

16

The Phthalocyanine Prototype Derivative Alcian Blue Is the First Synthetic Agent with Selective Anti-Human Immunodeficiency Virus Activity Due to Its gp120 Glycan-Binding Potential?  

PubMed Central

Alcian Blue (AB), a phthalocyanine derivative, is able to prevent infection by a wide spectrum of human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus strains in various cell types [T cells, (co)receptor-transfected cells, and peripheral blood mononuclear cells]. With the exception of herpes simplex virus, AB is inactive against a broad variety of other (DNA and RNA) viruses. Time-of-addition studies show that AB prevents HIV-1 infection at the virus entry stage, exactly at the same time as carbohydrate-binding agents do. AB also efficiently prevents fusion between persistently HIV-1-infected HUT-78 cells and uninfected (CD4+) lymphocytes, DC-SIGN-directed HIV-1 capture, and subsequent transmission to uninfected (CD4+) T lymphocytes. Prolonged passaging of HIV-1 at dose-escalating concentrations of AB resulted in the selection of mutant virus strains in which several N-glycans of the HIV-1 gp120 envelope were deleted and in which positively charged amino acid mutations in both gp120 and gp41 appeared. A mutant virus strain in which four N-glycans were deleted showed a 10-fold decrease in sensitivity to the inhibitory effect of AB. These data suggest that AB is likely endowed with carbohydrate-binding properties and can be considered an important lead compound in the development of novel synthetic nonpeptidic antiviral drugs targeting the glycans of the envelope of HIV. PMID:19721061

François, Katrien O.; Pannecouque, Christophe; Auwerx, Joeri; Lozano, Virginia; Pérez-Pérez, Maria-Jésus; Schols, Dominique; Balzarini, Jan

2009-01-01

17

Use of standardized SCID-hu Thy/Liv mouse model for preclinical efficacy testing of anti-human immunodeficiency virus type 1 compounds.  

PubMed Central

We have developed standardized procedures and practices for infection of SCID-hu Thy/Liv mice with human immunodeficiency virus type 1 for the prophylactic administration of antiviral compounds and for evaluation of the antiviral effect in vivo. Endpoint analyses included quantitation of viral load by intracellular p24 enzyme-linked immunosorbent assay, DNA PCR for the presence of proviral genomes, flow cytometry to measure the representation of CD4+ and CD8+ cells, and cocultivation for the isolation of virus. Efficacy tests in this model are demonstrated with the nucleoside analogs zidovudine and dideoxyinosine and with the nonnucleoside reverse transcriptase inhibitor nevirapine. This small-animal model should be particularly useful in the preclinical prioritization of lead compounds within a common chemical class, in the evaluation of alternative in vivo dosing regimens, and in the determination of appropriate combination therapy in vivo. PMID:8851606

Rabin, L; Hincenbergs, M; Moreno, M B; Warren, S; Linquist, V; Datema, R; Charpiot, B; Seifert, J; Kaneshima, H; McCune, J M

1996-01-01

18

Quinqueginsin, a Novel Protein with Anti-Human Immunodeficiency Virus, Antifungal, Ribonuclease and Cell-Free Translation-Inhibitory Activities from American Ginseng Roots  

Microsoft Academic Search

A homodimeric protein designated quinqueginsin, with a molecular weight of 53 kDa, has been isolated from the roots of American ginseng Panax quinquefolium. It was unadsorbed on DEAE cellulose in low ionic strength and neutral pH, and adsorbed on Affigel blue gel and SP-Sepharose under similar conditions. Its N-terminal sequence bore similarity to those of plant ribosome inactivating proteins and

H. X. Wang; T. B. Ng

2000-01-01

19

Design, intracellular expression, and activity of a human anti-human immunodeficiency virus type 1 gp120 single-chain antibody.  

PubMed Central

A single-chain antibody, derived from a human monoclonal antibody that recognizes the CD4 binding region of the human immunodeficiency virus type 1 (HIV-1) envelope protein, has been designed for intracellular expression in eukaryotic cells. The single-chain antibody is composed of an immunoglobulin heavy-chain leader sequence and heavy- and light-chain variable regions that are joined by an interchain linker. The antibody is stably expressed and retained in the endoplasmic reticulum and is not toxic to the cells. The antibody binds to the envelope protein within the cell and inhibits processing of the envelope precursor and syncytia formation. The infectivity of the HIV-1 particles produced by cells that express the single-chain antibody is substantially reduced. These studies illustrate the feasibility of designing antibodies that bind and inactivate molecules intracellularly. Antibodies that act on target molecules within cells should provide a useful tool for research as well as for control of infectious and other diseases. Images Fig. 1 Fig. 2 Fig. 3 PMID:8356098

Marasco, W A; Haseltine, W A; Chen, S Y

1993-01-01

20

Novel derivatives of phenethyl-5-bromopyridylthiourea and dihydroalkoxybenzyloxopyrimidine are dual-function spermicides with potent anti-human immunodeficiency virus activity.  

PubMed

Sexually active women represent the fastest growing HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) risk group. In an effort to develop a vaginal microbicidal contraceptive potentially capable of preventing HIV transmission as well as providing fertility control, we have synthesized novel non-nucleoside inhibitors (NNIs) of HIV-1 reverse transcriptase (RT) and examined them for dual-function anti-HIV and spermicidal activity. Structure-based drug design by use of a computer docking procedure for the NNI binding pocket generated from nine RT-NNI crystal structures led to the synthesis of three novel NNIs: N-[2-(2, 5-dimethoxyphenethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (D-PBT); N-[2-(2-fluorophenethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (F-PBT); and 5-isopropyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-on e (S-DABO). The anti-HIV activity of these NNIs was compared with that of trovirdine and virucidal/spermicide, nonoxynol-9 (N-9), by measuring viral RT activity and p24 antigen production as markers of viral replication using HTLVIIIB-infected human peripheral blood mononuclear cells (PBMCs). The effects on sperm motion kinematics and sperm membrane integrity were examined by computer-assisted sperm analysis and by confocal laser scanning microscopy (CLSM), respectively. The growth-inhibitory effects of NNI versus N-9 against normal human ectocervical and endocervical epithelial cells were tested using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. All three NNIs were potent inhibitors of purified recombinant HIV RT and abrogated HIV replication in PBMCs at nanomolar concentrations (IC50 < 1 nM) when compared with N-9 or trovirdine (IC50 values of 2.2 microM and 0.007 microM, respectively). Two NNIs, F-PBT and S-DABO, also exhibited concentration- and time-dependent spermicidal activity. The drug concentration required to inhibit sperm motility by 50% (EC50 values) for the lead compound F-PBT versus N-9 was 147 microM and 81 microM, respectively. Sperm-immobilizing activity induced by F-PBT and S-DABO was rapid (t1/2 = 7-13 min) and irreversible. Unlike that of N-9, spermicidal activity of F-PBT and S-DABO was not accompanied by loss of acrosomal membrane as detected by fluorescent-lectin binding assay and CLSM. Whereas N-9 was cytotoxic to normal human ectocervical and endocervical cells at spermicidal doses, both F-PBT and S-DABO were selectively spermicidal. We conclude that as potent anti-HIV agents with spermicidal activity and reduced cytotoxicity, F-PBT and S-DABO show unique clinical potential to become the active ingredients of a vaginal contraceptive for women who are at high risk for acquiring HIV by heterosexual vaginal transmission. PMID:10330101

D'Cruz, O J; Uckun, F M

1999-06-01

21

A Fe(3+)/DNA complex induces an anti-human immunodeficiency virus factor(s) in CD4+ lymphocyte cell lines.  

PubMed

Numerous cytokines and chemokines are involved in inflammatory and immune response. Whereas some of them inhibit virus replication in vitro directly or increase the patients' T4-lymphocyte level, others effects are not so clear. Using human immunodeficiency virus (HIV) and cell cultures we have studied the antiviral effect of complexes of salmon DNA with metals and of a new factor(s) (antiviral factor, AVF) induced in cells by the complexes. The Fe3+/DNA complex possessed the highest antiviral activity. It was found that MT-2, MT-4, CEM and Jurkat cells treated with the complexes secreted AVF which inhibited the replication of nine HIV-1 isolates, was noncytotoxic and stimulated cell proliferation. AVF did not inactivate HIV. The molecular mass analysis of AVF showed that its antiviral activity is associated with its fraction of M(r) of 3 K. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of mRNA from MT-4 cells treated with the complexes showed an increase in the the expression of genes for interleukin-1 alpha (IL-1 alpha), tumour necrosis factor alpha (TNF-alpha) and TNF-beta while expression of genes for IL-1-beta, IL-2, IL-4, IL-6, IL-8. IL-10, IL-12; 35p, 40p, IL-13, GMCSF, GSF and RANTES was not detected at all. However, the anti-HIV activity of the cell culture supernatant in vitro cannot be explained by mere presence of the inflammatory substances mentioned above, because they do not possess such activity and their M(r) is higher than that of AVF. Our findings raise the possibility that AVF(s) may be involved in the mechanism of cell resistance against HIV. PMID:10672340

Nossik, D; Kaplina, E; Nossik, N; Kalnina, L; Tsutsumi, R; Miura, Y; Sera, K; Itoh, C; Sato, S; Lvov, D

1999-02-01

22

Anti-human immunodeficiency virus 1 (HIV-1) activities of 3-deazaadenosine analogs: increased potency against 3'-azido-3'-deoxythymidine-resistant HIV-1 strains.  

PubMed Central

3-Deazaadenosine (DZA), 3-deaza-(+/-)-aristeromycin (DZAri), and 3-deazaneplanocin A (DZNep) are powerful modulators of cellular processes. When tested against H9 cells infected acutely with two different strains of human immunodeficiency virus 1 (HIV-1) and in the chronically infected monocytoid cell lines U1 and THP-1, the 3-deazanucleosides caused a marked reduction in p24 antigen production. Similar reductions in p24 antigen were seen in phytohemagglutinin-stimulated peripheral blood mononuclear cells infected with clinical HIV-1 isolates. Strikingly, in comparing the therapeutic indices between the paired pre- and post-3'-azido-3'-deoxythymidine (AZT) treatment HIV-1 isolates, DZNep and neplanocin A showed an increase of 3- to 18-fold in their potency against AZT-resistant HIV-1 isolates. In H9 cells treated with DZNep and DZAri, the formation of triphosphate nucleotides of DZNep and DZAri was observed. The mode of action of DZNep and DZAri appears complex, at least in part, at the level of infectivity as shown by decreases in syncytia formation in HIV-1-infected H9 cells and at the level of transcription as both drugs inhibited the expression of basal or tat-induced HIV-1 long terminal repeat chloramphenicol acetyltransferase activity in stably transfected cell lines. Since DZNep induced in H9 cells a rapid expression of nuclear binding factors that recognize the AP-1 transcription site, the anti-HIV-1 activity of the DZA analogs could partly be the induction of critical factors in the host cells. Thus, the 3-deazanucleoside drugs belong to an unusual class of anti-HIV-1 drugs, which may have therapeutic potential, in particular against AZT-resistant strains. Images Fig. 4 Fig. 5 PMID:7816820

Mayers, D L; Mikovits, J A; Joshi, B; Hewlett, I K; Estrada, J S; Wolfe, A D; Garcia, G E; Doctor, B P; Burke, D S; Gordon, R K

1995-01-01

23

Maraviroc (UK-427,857), a Potent, Orally Bioavailable, and Selective Small-Molecule Inhibitor of Chemokine Receptor CCR5 with Broad-Spectrum Anti-Human Immunodeficiency Virus Type 1 Activity  

PubMed Central

Maraviroc (UK-427,857) is a selective CCR5 antagonist with potent anti-human immunodeficiency virus type 1 (HIV-1) activity and favorable pharmacological properties. Maraviroc is the product of a medicinal chemistry effort initiated following identification of an imidazopyridine CCR5 ligand from a high-throughput screen of the Pfizer compound file. Maraviroc demonstrated potent antiviral activity against all CCR5-tropic HIV-1 viruses tested, including 43 primary isolates from various clades and diverse geographic origin (geometric mean 90% inhibitory concentration of 2.0 nM). Maraviroc was active against 200 clinically derived HIV-1 envelope-recombinant pseudoviruses, 100 of which were derived from viruses resistant to existing drug classes. There was little difference in the sensitivity of the 200 viruses to maraviroc, as illustrated by the biological cutoff in this assay (= geometric mean plus two standard deviations [SD] of 1.7-fold). The mechanism of action of maraviroc was established using cell-based assays, where it blocked binding of viral envelope, gp120, to CCR5 to prevent the membrane fusion events necessary for viral entry. Maraviroc did not affect CCR5 cell surface levels or associated intracellular signaling, confirming it as a functional antagonist of CCR5. Maraviroc has no detectable in vitro cytotoxicity and is highly selective for CCR5, as confirmed against a wide range of receptors and enzymes, including the hERG ion channel (50% inhibitory concentration, >10 ?M), indicating potential for an excellent clinical safety profile. Studies in preclinical in vitro and in vivo models predicted maraviroc to have human pharmacokinetics consistent with once- or twice-daily dosing following oral administration. Clinical trials are ongoing to further investigate the potential of using maraviroc for the treatment of HIV-1 infection and AIDS. PMID:16251317

Dorr, Patrick; Westby, Mike; Dobbs, Susan; Griffin, Paul; Irvine, Becky; Macartney, Malcolm; Mori, Julie; Rickett, Graham; Smith-Burchnell, Caroline; Napier, Carolyn; Webster, Rob; Armour, Duncan; Price, David; Stammen, Blanda; Wood, Anthony; Perros, Manos

2005-01-01

24

Antibody to adhesion molecule LFA-1 enhances plasma neutralization of human immunodeficiency virus type 1.  

PubMed Central

We have shown that a monoclonal antibody to the cell surface adhesion molecule LFA-1 (CD18/CD11a) enhances plasma neutralization of a laboratory isolate (HIVMN) and a primary isolate (HIV28R) of human immunodeficiency virus type 1. Human phytohemagglutinin blasts were infected with HIVMN or HIV28R in the presence of plasma pooled from HIV-positive individuals (AIDS plasma) or immunoglobulin G from AIDS plasma alone or combined with a monoclonal antibody (MAb) to LFA-1. While AIDS plasma alone at a dilution of 1:1,250 neutralized HIVMN and HIV28R infection by 15 and 0%, respectively, in the presence of a saturating concentration of the MAb to LFA-1 the plasma neutralized both viruses by more than 80% at this dilution. Immunoglobulin G purified from AIDS plasma, when used in combination with the MAb to LFA-1, showed the same synergistic effect in HIV neutralization as seen with the AIDS plasma and anti-LFA-1. The MAb against LFA-1 partially neutralized both viral isolates (45 to 55%) on its own. These results demonstrate significant synergy between the plasma and antibody against LFA-1 in the neutralization of HIV. The observations therefore suggest an important role for adhesion molecules in HIV infectivity and transmission. The results have implications for the recently observed host effect on HIV susceptibility to antibody neutralization. PMID:7541842

Gomez, M B; Hildreth, J E

1995-01-01

25

Potent Human Immunodeficiency Virus-Neutralizing and Complement Lysis Activities of Antibodies Are Not Obligatorily Linked? †  

PubMed Central

To evaluate the contribution of complement-mediated lysis to the in vivo activities of neutralizing antibodies, we analyzed the influence of complement activation on treatment success in a recent passive immunization trial with the neutralizing monoclonal antibodies 2G12, 2F5, and 4E10. Administration of monoclonal antibodies led to an immediate, high activation of the complement system even in the absence of viremia in the 14 participating human immunodeficiency virus-infected individuals. Lysis activity measured in patient plasma increased during passive immunization; however, the increases were modest and only partially attributable to the administration of antibodies. We found that unlike neutralization activity, lysis activity was not associated with treatment success in this trial. Compared to complement lysis mounted by the polyclonal antibody response in vivo, monoclonal antibodies were weak inducers of this activity, suggesting that polyclonal responses are more effective in reaching the required threshold of complement activation. Importantly, strong neutralization activity of the monoclonal antibodies did not predict complement lysis activity against patient and reference viruses, suggesting that these activities are not linked. In summary, our data support the notion that the in vivo activities of 2G12, 2F5, and 4E10 are likely due to direct neutralization or Fc receptor-mediated mechanisms such as phagocytosis and antibody-dependent cellular cytotoxicity. PMID:18234794

Huber, Michael; von Wyl, Viktor; Ammann, Christoph G.; Kuster, Herbert; Stiegler, Gabriela; Katinger, Hermann; Weber, Rainer; Fischer, Marek; Stoiber, Heribert; Günthard, Huldrych F.; Trkola, Alexandra

2008-01-01

26

Modeling Virus- and Antibody-Specific Factors to Predict Human Immunodeficiency Virus (HIV-1) Neutralization Efficiency  

PubMed Central

SUMMARY Efforts to prevent human immunodeficiency virus (HIV-1) infection would benefit from understanding the factors that govern virus neutralization by antibodies. We present a mechanistic model for HIV-1 neutralization that includes both virus and antibody parameters. Variations in epitope integrity on the viral envelope glycoprotein (Env) trimer and Env reactivity to bound antibody influence neutralization susceptibility. In addition, we define an antibody-specific parameter, the perturbation factor (PF), that describes the degree of conformational change in the Env trimer required for a given antibody to bind. Minimally perturbing (low-PF) antibodies can efficiently neutralize viruses with a broad range of Env reactivities due to fast on-rates and high affinity for Env. Highly perturbing (high-PF) antibodies inhibit only viruses with reactive (perturbation-sensitive) Envs, often through irreversible mechanisms. Accounting for these quantifiable viral and antibody-associated parameters helps to predict the observed profiles of HIV-1 neutralization by antibodies with a wide range of potencies. PMID:24237700

Haim, Hillel; Salas, Ignacio; McGee, Kathleen; Eichelberger, Noah; Winter, Elizabeth; Pacheco, Beatriz; Sodroski, Joseph

2013-01-01

27

Role of Human Immunodeficiency Virus Type 1 Envelope Structure in the Induction of Broadly Neutralizing Antibodies  

PubMed Central

Very soon after the discovery of neutralizing antibodies (NAbs) toward human immunodeficiency virus type 1 (HIV-1) infection, it became apparent that characterization of these NAbs would be an important step in finding a cure for or a vaccine to eradicate HIV-1. Since the initial description of broadly cross-clade NAbs naturally produced in HIV-1 patients, numerous studies have described new viral targets for these antibodies. More recently, studies concerning new groups of patients able to control their viremia, such as long-term nonprogressors (LTNPs) or elite controllers, have described the generation of numerous envelope-targeted NAbs. Recent studies have marked a new stage in research on NAbs with the description of antibodies obtained from a worldwide screening of HIV-positive patients. These studies have permitted the discovery of NAb families with great potential for both neutralization and neutralization breadth, such as PG, PGT, CH, and highly active agonistic anti-CD4 binding site antibodies (HAADs), of which VRC01 and its variants are members. These antibodies are able to neutralize more than 80% of circulating strains without any autoreactivity and can be rapidly integrated into clinical trials in order to test their protective potential. In this review, we will focus on new insights into HIV-1 envelope structure and their implications for the generation of potent NAbs. PMID:23015715

Benjelloun, F.; Lawrence, P.; Verrier, B.; Genin, C.

2012-01-01

28

Determination of a Statistically Valid Neutralization Titer in Plasma That Confers Protection against Simian-Human Immunodeficiency Virus Challenge following Passive Transfer of High-Titered Neutralizing Antibodies  

Microsoft Academic Search

We previously reported that high-titered neutralizing antibodies directed against the human immunodefi- ciency virus type 1 (HIV-1) envelope can block the establishment of a simian immunodeficiency virus (SIV)\\/ HIV chimeric virus (SHIV) infection in two monkeys following passive transfer (R. Shibata et al., Nat. Med. 5:204-210, 1999). In the present study, increasing amounts of neutralizing immunoglobulin G (IgG) were administered

Yoshiaki Nishimura; Tatsuhiko Igarashi; Nancy Haigwood; Reza Sadjadpour; Ron J. Plishka; Alicia Buckler-White; Riri Shibata; Malcolm A. Martin

2002-01-01

29

Breadth of Human Immunodeficiency Virus-Specific Neutralizing Activity in Sera: Clustering Analysis and Association with Clinical Variables ?  

PubMed Central

Induction of antibodies that neutralize a broad range of human immunodeficiency virus type 1 (HIV-1) isolates is a major goal of vaccine development. To study natural examples of broad neutralization, we analyzed sera from 103 HIV-1-infected subjects. Among progressor patients, 20% of sera neutralized more than 75% of a panel of 20 diverse viral isolates. Little activity was observed in sera from long-term nonprogressors (elite controllers). Breadth of neutralization was correlated with viral load, but not with CD4 count, history of past antiretroviral use, age, gender, race/ethnicity, or route of exposure. Clustering analysis of sera by a novel method identified a statistically robust subgrouping of sera that demonstrated broad and potent neutralization activity. PMID:19923174

Doria-Rose, Nicole A.; Klein, Rachel M.; Daniels, Marcus G.; O'Dell, Sijy; Nason, Martha; Lapedes, Alan; Bhattacharya, Tanmoy; Migueles, Stephen A.; Wyatt, Richard T.; Korber, Bette T.; Mascola, John R.; Connors, Mark

2010-01-01

30

Chimeric Gag-V3 Virus-Like Particles of Human Immunodeficiency Virus Induce Virus-Neutralizing Antibodies  

Microsoft Academic Search

A 41-kDa unprocessed human immunodeficiency virus 2 (HIV-2) gag precursor protein that has a deletion of a portion of the viral protease assembles as virus-like particles by budding through the cytoplasmic membrane of recombinant baculovirus-infected insect cells. We have constructed six different combinations of chimeric genes by coupling the truncated HIV-2 gag gene to the neutralizing domain (V3) or the

Lizhong Luo; Yan Li; Paula M. Cannon; Sunyoung Kim; C. Yong Kang

1992-01-01

31

Protective effects of broadly neutralizing immunoglobulin against homologous and heterologous equine infectious anemia virus infection in horses with severe combined immunodeficiency.  

PubMed

Using the equine infectious anemia virus (EIAV) lentivirus model system, we previously demonstrated protective effects of broadly neutralizing immune plasma in young horses (foals) with severe combined immunodeficiency (SCID). However, in vivo selection of a neutralization-resistant envelope variant occurred. Here, we determined the protective effects of purified immunoglobulin with more potent broadly neutralizing activity. Overall, protection correlated with the breadth and potency of neutralizing activity in vitro. Four of five SCID foals were completely protected against homologous challenge, while partial protection occurred following heterologous challenge. These results support the inclusion of broadly neutralizing antibodies in lentivirus control strategies. PMID:21543497

Taylor, Sandra D; Leib, Steven R; Wu, Wuwei; Nelson, Robert; Carpenter, Susan; Mealey, Robert H

2011-07-01

32

Cross-Clade Neutralization of Primary Isolates of Human Immunodeficiency Virus Type 1 by Human Monoclonal Antibodies and Tetrameric CD4IgG  

Microsoft Academic Search

We have tested three human monoclonal antibodies (MAbs) IgG1b12, 2G12, and 2F5) to the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1), and a tetrameric CD4-IgG molecule (CD4- IgG2), for the ability to neutralize primary HIV-1 isolates from the genetic clades A through F and from group O. Each of the reagents broadly and potently neutralized B-clade isolates. The

ALEXANDRA TRKOLA; AUDREY B. POMALES; HANNAH YUAN; BETTE KORBER; PAUL J. MADDON; GRAHAM P. ALLAWAY; HERMANN KATINGER; CARLOS F. BARBAS III; DENNIS R. BURTON; DAVID D. HO; ANDJOHN P. MOORE

1995-01-01

33

Identification and characterization of a neutralization site within the second variable region of human immunodeficiency virus type 1 gp120.  

PubMed Central

Two monoclonal antibodies designated BAT085 and G3-136 were raised by immunizing BALB/c mice with gp120 purified from human immunodeficiency virus type 1 (HIV-1) IIIB-infected H9 cell extracts. Among three HIV-1 laboratory isolates (IIIB, MN, and RF), BAT085 neutralized only IIIB infection of CEM-SS cells, whereas G3-136 neutralized both IIIB and RF. These antibodies also neutralized a few primary HIV-1 isolates in the infection of activated human peripheral blood mononuclear cells. In indirect immunofluorescence assays, BAT085 bound to H9 cells infected with IIIB or MN, while G3-136 bound to H9 cells infected with IIIB or RF, but not MN. Using sequence-overlapping synthetic peptides of HIV-1 IIIB gp120, the binding site of BAT085 and G3-136 was mapped to a peptidic segment in the V2 region (amino acid residues 169 to 183). The binding of these antibodies to immobilized gp120 was not inhibited by the antibodies directed to the principal neutralization determinant in the V3 region or to the CD4-binding domain of gp120. In a competition enzyme-linked immunosorbent assay, soluble CD4 inhibited G3-136 but not BAT085 from binding to gp120. Deglycosylation of gp120 by endo-beta-N-acetylglucosaminidase H or reduction of gp120 by dithiothreitol diminished its reactivity with G3-136 but not with BAT085. These results indicate that the V2 region of gp120 contains multiple neutralization determinants recognized by antibodies in both a conformation-dependent and -independent manner. PMID:1370558

Fung, M S; Sun, C R; Gordon, W L; Liou, R S; Chang, T W; Sun, W N; Daar, E S; Ho, D D

1992-01-01

34

Epitopes for Broad and Potent Neutralizing Antibody Responses during Chronic Infection with Human Immunodeficiency Virus Type 1  

PubMed Central

Neutralizing antibody (nAb) response is sporadic and has limited potency and breadth during infection with human immunodeficiency virus type 1 (HIV-1). In rare cases, broad and potent nAbs are actually induced in vivo. Identifying specific epitopes targeted by such broad and potent nAb response is valuable in guiding the design of a prophylactic vaccine aimed to induce nAb. In this study, we have defined neutralizing epitope usage in 7 out of 17 subjects with broad and potent nAbs by using targeted mutagenesis in known neutralizing epitopes of HIV-1 glycoproteins and by using in vitro depletion of serum neutralizing activity by various recombinant HIV-1 glycoproteins. Consistent with recent reports, the CD4 binding site (CD4BS) is targeted by nAbs in vivo (4 of the 7 subjects with defined neutralizing epitopes). The new finding from this study is that epitopes in the gp120 outer domain are also targeted by nAbs in vivo (5 of the 7 subjects). The outer domain epitopes include glycan-dependent epitopes (2 subjects), conserved non-linear epitope in the V3 region (2 subjects), and a CD4BS epitope composed mainly of the elements in the outer domain (1 subject). Importantly, we found indication for epitope poly-specificity, a dual usage of the V3 and CD4BS epitopes, in only one subject. This study provides a more complete profile of epitope usage for broad and potent nAb responses during HIV-1 infection. PMID:19922969

Nandi, Avishek; Lavine, Christine L.; Wang, Pengcheng; Lipchina, Inna; Goepfert, Paul A.; Shaw, George M.; Tomaras, Georgia D.; Montefiori, David C.; Haynes, Barton F.; Easterbrook, Philippa; Robinson, James E.; Sodroski, Joseph G.; Yang, Xinzhen

2009-01-01

35

Proline-rich tandem repeats of antibody complementarity-determining regions bind and neutralize human immunodeficiency virus type 1 particles.  

PubMed Central

The proline-rich tandem repeat domain of human mucin MUC1 forms an extended structure containing large repeating loops that are crested by a turn. We show that the repeating-loop structure of MUC1 can be replaced by an antibody complementarity-determining region loop of a human immunodeficiency virus type 1 (HIV-1)-specific neutralizing antibody to create a chimeric, multivalent, mucin-like, anti-HIV-1 compound. We used 8 residues of an antibody molecule to replace 8 of 20 residues of the MUC1 tandem-repeat sequence. The antiviral peptide discussed here contains three copies of a 20-residue tandem repeat, (IYYDYEEDPAPGSTAPPAHG)3, for a total of 60 residues. We demonstrate that the mucin-antibody chimera retains the binding specificity of the parent antibody (monoclonal antibody F58), GPGR of the HIV-1 gp120 V3 neutralizing epitope, and the ability to neutralize virus particles. In inhibition enzyme-linked immunosorbent assay, the mucin-antibody chimeric peptide could inhibit 71 to 84% of binding to a V3 loop peptide by monoclonal antibodies known to be specific for GPGR in the V3 loop. The mucin-antibody chimeric peptide could also inhibit monoclonal antibody binding to native gp120 captured from virus particles. In addition, the chimeric peptide neutralized the homologous HIV-IIIB virus in a standard neutralization assay. The methods of antiviral peptide design and construction presented here are general and theoretically limited only by the size of the antibody repertoire. This approach could be used to synthesize peptides for a variety of therapeutic applications. PMID:8794290

Fontenot, J D; Zacharopoulos, V R; Phillips, D M

1996-01-01

36

Impact of amino acid substitutions in the V2 and C2 regions of human immunodeficiency virus type 1 CRF01_AE envelope glycoprotein gp120 on viral neutralization susceptibility to broadly neutralizing antibodies specific for the CD4 binding site  

PubMed Central

Background The CD4 binding site (CD4bs) of envelope glycoprotein (Env) gp120 is a functionally conserved, important target of anti-human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies. Two neutralizing human monoclonal antibodies, IgG1 b12 (b12) and VRC01, are broadly reactive neutralizing antibodies which recognize conformational epitopes that overlap the CD4bs of Env gp120; however, many CRF01_AE viruses are resistant to neutralization mediated by these antibodies. We examined the mechanism underlying the b12 resistance of the viruses using CRF01_AE Env (AE-Env)-recombinant viruses in this study. Results Our results showed that an amino acid substitution at position 185 in the V2 region of gp120 played a crucial role in regulating the b12 susceptibility of AE-Env-recombinant viruses by cooperating with 2 previously reported potential N-linked glycosylation (PNLG) sites at positions 186 (N186) and 197 (N197) in the V2 and C2 regions of Env gp120. The amino acid residue at position 185 and 2 PNLG sites were responsible for the b12 resistance of 21 of 23 (>91%) AE-Env clones tested. Namely, the introduction of aspartic acid at position 185 (D185) conferred b12 susceptibility of 12 resistant AE-Env clones in the absence of N186 and/or N197, while the introduction of glycine at position 185 (G185) reduced the b12 susceptibility of 9 susceptible AE-Env clones in the absence of N186 and/or N197. In addition, these amino acid mutations altered the VRC01 susceptibility of many AE-Env clones. Conclusions We propose that the V2 and C2 regions of AE-Env gp120 contain the major determinants of viral resistance to CD4bs antibodies. CRF01_AE is a major circulating recombinant form of HIV-1 prevalent in Southeast Asia. Our data may provide important information to understand the molecular mechanism regulating the neutralization susceptibility of CRF01_AE viruses to CD4bs antibodies. PMID:24758333

2014-01-01

37

A simple procedure to generate chimeric Pr55gag virus-like particles expressing the principal neutralization domain of human immunodeficiency virus type  

Microsoft Academic Search

The Pr55gag human immunodeficiency virus type 1 (HIV-1) precursor protein that is capable of auto-assembling was used as a carrier for a consensus sequence of the principal neutralization domain (PND) of the HIV-1 envelope. For this purpose, a modified HTV-1 gag gene with deletion of the sequence encoding a previously described p24 epitope (amino acids 196–228 of Pr55gag) was first

Denys Brand; François Mallet; Catherine Truong; Philippe Roingeard; Alain Goudeau; Francis Barin

1995-01-01

38

Neutralizing Antibodies Do Not Mediate Suppression of Human Immunodeficiency Virus Type 1 in Elite Suppressors or Selection of Plasma Virus Variants in Patients on Highly Active Antiretroviral Therapy  

Microsoft Academic Search

Neutralizing antibodies (NAb) against autologous virus can reach high titers in human immunodeficiency virus type 1 (HIV-1)-infected patients with progressive disease. Less is known about the role of NAb in HIV-1-infected patients with viral loads of <50 copies\\/ml of plasma, including patients on effective highly active antiretroviral therapy (HAART) and elite suppressors, who control HIV-1 replication without antiretroviral therapy. In

Justin R. Bailey; Kara G. Lassen; Hung-Chih Yang; Thomas C. Quinn; Stuart C. Ray; Joel N. Blankson; Robert F. Siliciano

2006-01-01

39

Human Immunodeficiency Virus Type 1 Neutralization Epitope with Conserved Architecture Elicits Early Type-Specific Antibodies in Experimentally Infected Chimpanzees  

Microsoft Academic Search

Chimpanzees are susceptible to infection by divergent strains of human immunodeficiency virus type 1 (HIV-1), none of which cause clinical or immunological abnormalities. Chimpanzees were inoculated with one of four strains of HIV-1: human T-lymphotropic virus (HTLV) type IIIB, lymphadenopathy virus (LAV) type 1, HTLV type IIIRF, or an isolate from the brain of a patient with acquired immunodeficiency syndrome.

Jaap Goudsmit; Christine Debouck; Rob H. Meloen; Lia Smit; Margreet Bakker; David M. Asher; Axel V. Wolff; Clarence J. Gibbs; D. Carleton Gajdusek

1988-01-01

40

Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian–human immunodeficiency virus infection  

Microsoft Academic Search

Although maternal human immunodeficiency virus type 1 (HIV-1) transmission occurs during gestation, intrapartum and postpartum (by breast-feeding), 50–70% of all infected children seem to acquire HIV-1 shortly before or during delivery. Epidemiological evidence indicates that mucosal exposure is an important aspect of intrapartum HIV transmission. A simian immunodeficiency virus (SIV) macaque model has been developed that mimics the mucosal exposure

Timothy W. Baba; Vladimir Liska; Regina Hofmann-Lehmann; Josef Vlasak; Weidong Xu; Seyoum Ayehunie; Lisa A. Cavacini; Marshall R. Posner; Hermann Katinger; Gabriela Stiegler; Bruce J. Bernacky; Tahir A. Rizvi; Russell Schmidt; Lori R. Hill; Michale E. Keeling; Yichen Lu; Joel E. Wright; Ting-Chao Chou; Ruth M. Ruprecht

2000-01-01

41

A Cell Line-Based Neutralization Assay for Primary Human Immunodeficiency Virus Type 1 Isolates That Use either the CCR5 or the CXCR4 Coreceptor  

PubMed Central

We describe here a cell line-based assay for the evaluation of human immunodeficiency virus type 1 (HIV-1) neutralization. The assay is based on CEM.NKR cells, transfected to express the HIV-1 coreceptor CCR5 to supplement the endogenous expression of CD4 and the CXCR4 coreceptor. The resulting CEM.NKR-CCR5 cells efficiently replicate primary HIV-1 isolates of both R5 and X4 phenotypes. A comparison of the CEM.NKR-CCR5 cells with mitogen-activated peripheral blood mononuclear cells (PBMC) in neutralization assays with sera from HIV-1-infected individuals or specific anti-HIV-1 monoclonal antibodies shows that the sensitivity of HIV-1 neutralization is similar in the two cell types. The CEM.NKR-CCR5 cell assay, however, is more convenient to perform and eliminates the donor-to-donor variation in HIV-1 replication efficiency, which is one of the principal drawbacks of the PBMC-based neutralization assay. We suggest that this new assay is suitable for the general measurement of HIV-1 neutralization by antibodies. PMID:10516002

Trkola, Alexandra; Matthews, Jamie; Gordon, Cynthia; Ketas, Tom; Moore, John P.

1999-01-01

42

A cell line-based neutralization assay for primary human immunodeficiency virus type 1 isolates that use either the CCR5 or the CXCR4 coreceptor.  

PubMed

We describe here a cell line-based assay for the evaluation of human immunodeficiency virus type 1 (HIV-1) neutralization. The assay is based on CEM.NKR cells, transfected to express the HIV-1 coreceptor CCR5 to supplement the endogenous expression of CD4 and the CXCR4 coreceptor. The resulting CEM.NKR-CCR5 cells efficiently replicate primary HIV-1 isolates of both R5 and X4 phenotypes. A comparison of the CEM.NKR-CCR5 cells with mitogen-activated peripheral blood mononuclear cells (PBMC) in neutralization assays with sera from HIV-1-infected individuals or specific anti-HIV-1 monoclonal antibodies shows that the sensitivity of HIV-1 neutralization is similar in the two cell types. The CEM.NKR-CCR5 cell assay, however, is more convenient to perform and eliminates the donor-to-donor variation in HIV-1 replication efficiency, which is one of the principal drawbacks of the PBMC-based neutralization assay. We suggest that this new assay is suitable for the general measurement of HIV-1 neutralization by antibodies. PMID:10516002

Trkola, A; Matthews, J; Gordon, C; Ketas, T; Moore, J P

1999-11-01

43

Increased sensitivity to CD4 binding site-directed neutralization following in vitro propagation on primary lymphocytes of a neutralization-resistant human immunodeficiency virus IIIB strain isolated from an accidentally infected laboratory worker.  

PubMed

We previously described the adaptation of the neutralization-sensitive human immunodeficiency virus type 1 (HIV-1) strain IIIB to a neutralization-resistant phenotype in an accidentally infected laboratory worker. During long-term propagation of this resistant isolate, designated FF3346, on primary peripheral blood leukocytes in vitro, an HIV-1 variant appeared that had regained sensitivity to neutralization by soluble CD4 (sCD4) and the broadly neutralizing monoclonal antibody b12. When an early passage of FF3346 was subjected to limiting-dilution culture in peripheral blood mononuclear cells, eight virus variants with various degrees of neutralization resistance were isolated. Two of them, the sCD4 neutralization-resistant variant LW_H8(res) and the sCD4 neutralization-sensitive variant LW_G9(sens), were selected for further study. Interestingly, these two viruses were equally resistant to neutralization by agents that recognize domains other than the CD4 binding site. Site-directed mutagenesis revealed that the increased neutralization sensitivity of variant LW_G9(sens) resulted from only two changes, an Asn-to-Ser substitution at position 164 in the V2 loop and an Ala-to-Glu substitution at position 370 in the C3 domain of gp120. In agreement with this notion, the affinity of b12 for monomeric gp120 containing the N164S and A370E substitutions in the background of the molecular clone LW_H8(res) was higher than its affinity for the parental gp120. Surprisingly, no correlation was observed between CD4 binding affinity for monomeric gp120 and the level of neutralization resistance, suggesting that differences in sCD4 neutralization sensitivity between these viruses are only manifested in the context of the tertiary or quaternary structure of gp120 on the viral surface. The results obtained here indicate that the neutralization-sensitive strain IIIB can become neutralization resistant in vivo under selective pressure by neutralizing antibodies but that this resistance may be easily reversed in the absence of immunological pressure. PMID:15140962

Beaumont, Tim; Quakkelaar, Esther; van Nuenen, Ad; Pantophlet, Ralph; Schuitemaker, Hanneke

2004-06-01

44

Neutralizing Polyclonal IgG Present during Acute Infection Prevents Rapid Disease Onset in Simian-Human Immunodeficiency Virus SHIVSF162P3-Infected Infant Rhesus Macaques  

PubMed Central

Simian-human immunodeficiency virus (SHIV) models for human immunodeficiency virus (HIV) infection have been widely used in passive studies with HIV neutralizing antibodies (NAbs) to test for protection against infection. However, because SHIV-infected adult macaques often rapidly control plasma viremia and any resulting pathogenesis is minor, the model has been unsuitable for studying the impact of antibodies on pathogenesis in infected animals. We found that SHIVSF162P3 infection in 1-month-old rhesus macaques not only results in high persistent plasma viremia but also leads to very rapid disease progression within 12 to 16 weeks. In this model, passive transfer of high doses of neutralizing IgG (SHIVIG) prevents infection. Here, we show that at lower doses, SHIVIG reduces both plasma and peripheral blood mononuclear cell (PBMC)-associated viremia and mitigates pathogenesis in infected animals. Moreover, production of endogenous NAbs correlated with lower set-point viremia and 100% survival of infected animals. New SHIV models are needed to investigate whether passively transferred antibodies or antibodies elicited by vaccination that fall short of providing sterilizing immunity impact disease progression or influence immune responses. The 1-month-old rhesus macaque SHIV model of infection provides a new tool to investigate the effects of antibodies on viral replication and clearance, mechanisms of B cell maintenance, and the induction of adaptive immunity in disease progression. PMID:23885083

Jaworski, J. Pablo; Kobie, James; Brower, Zachary; Malherbe, Delphine C.; Landucci, Gary; Sutton, William F.; Guo, Biwei; Reed, Jason S.; Leon, Enrique J.; Engelmann, Flora; Zheng, Bo; Legasse, Al; Park, Byung; Dickerson, Mary; Lewis, Anne D.; Colgin, Lois M. A.; Axthelm, Michael; Messaoudi, Ilhem; Sacha, Jonah B.; Burton, Dennis R.; Forthal, Donald N.; Hessell, Ann J.

2013-01-01

45

Neutralization of Infectivity of Diverse R5 Clinical Isolates of Human Immunodeficiency Virus Type 1 by gp120-Binding 2?F-RNA Aptamers  

PubMed Central

Human immunodeficiency virus type 1 (HIV-1) has evolved a number of strategies to resist current antiretroviral drugs and the selection pressures of humoral and cellular adaptive immunity. For example, R5 strains, which use the CCR5 coreceptor for entry and are the dominant viral phenotype for HIV-1 transmission and AIDS pathogenesis, are relatively resistant to neutralization by antibodies, as are other clinical isolates. In order to overcome these adaptations, we raised nucleic acid aptamers to the SU glycoprotein (gp120) of the R5 strain, HIV-1Ba-L. These not only bound gp120 with high affinity but also neutralized HIV-1 infectivity in human peripheral blood mononuclear cells (PBMCs) by more than 1,000-fold. Furthermore, these aptamers were able to neutralize the infectivity of R5 clinical isolates of HIV-1 derived from group M (subtypes A, C, D, E, and F) and group O. One aptamer defined a site on gp120 that overlaps partially with the conserved, chemokine receptor-binding, CD4-induced epitope recognized by monoclonal antibody 17b. In contrast to the antibody, the site is accessible to aptamer in the absence of CD4 binding. Neutralizing aptamers such as this could be exploited to provide leads in developing alternative, efficacious anti-HIV-1 drugs and lead to a deeper understanding of the molecular interactions between the virus and its host cell. PMID:14610191

Khati, Makobetsa; Schüman, Michael; Ibrahim, Jamal; Sattentau, Quentin; Gordon, Siamon; James, William

2003-01-01

46

Neutralization of infectivity of diverse R5 clinical isolates of human immunodeficiency virus type 1 by gp120-binding 2'F-RNA aptamers.  

PubMed

Human immunodeficiency virus type 1 (HIV-1) has evolved a number of strategies to resist current antiretroviral drugs and the selection pressures of humoral and cellular adaptive immunity. For example, R5 strains, which use the CCR5 coreceptor for entry and are the dominant viral phenotype for HIV-1 transmission and AIDS pathogenesis, are relatively resistant to neutralization by antibodies, as are other clinical isolates. In order to overcome these adaptations, we raised nucleic acid aptamers to the SU glycoprotein (gp120) of the R5 strain, HIV-1(Ba-L). These not only bound gp120 with high affinity but also neutralized HIV-1 infectivity in human peripheral blood mononuclear cells (PBMCs) by more than 1,000-fold. Furthermore, these aptamers were able to neutralize the infectivity of R5 clinical isolates of HIV-1 derived from group M (subtypes A, C, D, E, and F) and group O. One aptamer defined a site on gp120 that overlaps partially with the conserved, chemokine receptor-binding, CD4-induced epitope recognized by monoclonal antibody 17b. In contrast to the antibody, the site is accessible to aptamer in the absence of CD4 binding. Neutralizing aptamers such as this could be exploited to provide leads in developing alternative, efficacious anti-HIV-1 drugs and lead to a deeper understanding of the molecular interactions between the virus and its host cell. PMID:14610191

Khati, Makobetsa; Schüman, Michael; Ibrahim, Jamal; Sattentau, Quentin; Gordon, Siamon; James, William

2003-12-01

47

21 CFR 660.50 - Anti-Human Globulin.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Anti-Human Globulin. 660.50 Section 660.50...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ...SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

2010-04-01

48

21 CFR 660.50 - Anti-Human Globulin.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2010-04-01 true Anti-Human Globulin. 660.50 Section 660.50...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ...SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

2011-04-01

49

21 CFR 660.50 - Anti-Human Globulin.  

...2014-04-01 2014-04-01 false Anti-Human Globulin. 660.50 Section 660.50...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ...SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

2014-04-01

50

21 CFR 660.50 - Anti-Human Globulin.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Anti-Human Globulin. 660.50 Section 660.50...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ...SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

2013-04-01

51

21 CFR 660.50 - Anti-Human Globulin.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Anti-Human Globulin. 660.50 Section 660.50...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ...SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

2012-04-01

52

Highly efficient neutralization by plasma antibodies from human immunodeficiency virus type-1 infected individuals on antiretroviral drug therapy.  

PubMed

Little is known about the neutralizing antibodies induced in HIV-1 patients on antiretroviral treatment, which constitute an interesting group of individuals with improved B cell profile. Plasma samples from 34 HIV-1 seropositive antiretroviral drug treated (ART) patients were tested for neutralization against a panel of 14 subtype-A, B and C tier 1 and tier 2 viruses in TZM-bl assay. Of the 34 plasma samples, remarkably all the plasma samples were able to neutralize at least one virus while 32 (94 %) were found to neutralize ?50 % viruses tested. In terms of overall neutralization frequency, approximately 86 %, 68 % and 17 % of the virus/plasma combinations showed 50 % neutralizing activity at 1 > 60, 1 ? 200 and 1 ??2000 dilutions respectively. The improvement in neutralizing activity was shown to be associated with ART in two follow up patients. The neutralization of viruses by two representative plasma samples, AIIMS221 and AIIMS265, was exclusively mediated by immunoglobulin G fractions independent of ART drugs and IgG retained cross-reactive binding to recombinant gp120 proteins. We observed a positive trend of neutralization with duration of ART (p = 0.06), however no such correlation was found with clinical and immunological variables like CD4 count (p = 0.35), viral load (p = 0.09) and plasma total IgG (p = 0.46). Our study suggests that the plasma antibodies from ART patients display high neutralizing activity most likely due to an improved B cell function induced by ART despite low antigenic stimulation. PMID:24682667

Andrabi, Raiees; Makhdoomi, M A; Kumar, Rajesh; Bala, Manju; Parray, Hilal; Gupta, Arjun; Kotnala, Ankita; Thirumurthy, Velpandian; Luthra, Kalpana

2014-05-01

53

Strain specificity and binding affinity requirements of neutralizing monoclonal antibodies to the C4 domain of gp120 from human immunodeficiency virus type 1.  

PubMed Central

The binding properties of seven CD4-blocking monoclonal antibodies raised against recombinant gp120 of human immunodeficiency virus type 1 strain MN (HIV-1MN) and two CD4-blocking monoclonal antibodies to recombinant envelope glycoproteins gp120 and gp160 of substrain IIIB of HIVLAI were analyzed. With a panel of recombinant gp120s from seven diverse HIV-1 isolates, eight of the nine antibodies were found to be strain specific and one was broadly cross-reactive. Epitope mapping revealed that all nine antibodies bound to epitopes located in the fourth conserved domain (C4) of gp120. Within this region, three distinct epitopes could be identified: two were polymorphic between HIV-1 strains, and one was highly conserved. Studies with synthetic peptides demonstrated that the conserved epitope, recognized by antibody 13H8, was located between residues 431 and 439. Site-directed mutagenesis of gp120 demonstrated that residue 429 and/or 432 was critical for the binding of the seven antibodies to gp120 from HIV-1MN. Similarly, residues 423 and 429 were essential for the binding of monoclonal antibody 5C2 raised against gp120 from HIV-1IIIB. The amino acids located at positions 423 and 429 were found to vary between strains of HIV-1 as well as between molecular clones derived from the MN and LAI isolates of HIV-1. Polymorphism at these positions prevented the binding of virus-neutralizing monoclonal antibodies and raised the possibility that HIV-1 neutralization serotypes may be defined on the basis of C4 domain sequences. Analysis of the binding characteristics of the CD4-blocking antibodies demonstrated that their virus-neutralizing activity was directly proportional to their gp120-binding affinity. These studies account for the strain specificity of antibodies to the C4 domain of gp120 and demonstrate for the first time that antibodies to this region can be as effective as those directed to the principal neutralizing determinant (V3 domain) in neutralizing HIV-1 infectivity. Images PMID:7690420

Nakamura, G R; Byrn, R; Wilkes, D M; Fox, J A; Hobbs, M R; Hastings, R; Wessling, H C; Norcross, M A; Fendly, B M; Berman, P W

1993-01-01

54

Human immunodeficiency virus 1. Predominance of a group-specific neutralizing epitope that persists despite genetic variation  

PubMed Central

HIV-1 is known to show a high degree of genetic diversity, which may have major implications for disease pathogenesis and prevention. If every divergent isolate represented a distinct serotype, then effective vaccination might be impossible. However, using a sensitive new plaque- forming assay for HIV-1, we have found that most infected patients make neutralizing antibodies, predominantly to a group-specific epitope shared among three highly divergent isolates. This epitope persists among divergent isolates and rarely mutates, despite the rapid overall mutation rate of HIV-1, suggesting that it may participate in an essential viral function. These findings, plus the rarity of reinfections among these patients, suggest that HIV-1 may be more susceptible to a vaccine strategy based on a group-specific neutralizing epitope than was previously suspected. PMID:2478654

1989-01-01

55

Neutralizing monoclonal antibodies to human immunodeficiency virus type 1 do not inhibit viral transcytosis through mucosal epithelial cells.  

PubMed

HIV-1 transcytosis has been proposed as a potential mechanism allowing the virus to cross the epithelium during mucosal transmission. Epitopes of the HIV-1 envelope involved in this process have not been identified yet. Here, we assessed a large panel of HIV neutralizing antibodies recognizing well-characterized epitopes of the HIV-1 envelope for their ability to block HIV-1 transcytosis across a confluent epithelial monolayer. We found that all of the 13 HIV-1-specific monoclonal antibodies tested in the present study, including the three broadly neutralizing antibodies 2F5, 2G12 and IgG1b12, lacked the ability to inhibit transcytosis of cell-free and cell-associated R5- as X4-tropic HIV-1 across a tight and polarized monolayer of HEC-1 epithelial cells. In contrast, anti-gp160 polyclonal antibodies purified from serum or breast milk of HIV-1-infected individuals potently inhibited HIV-1 transcytosis. Furthermore, polymeric S-IgA exhibited similar ability to inhibit transcytosis compared to IgG despite their lower anti-gp160 specific activity. Together, these results demonstrate that the major neutralizing envelope epitopes of HIV-1 are not involved in HIV-1 transcytosis, and suggest that surface agglutination of virus particles may participate to the blocking effect observed with both polyclonal and polymeric anti-gp160 immunoglobulins. PMID:17920650

Chomont, Nicolas; Hocini, Hakim; Gody, Jean-Chrysostome; Bouhlal, Hicham; Becquart, Pierre; Krief-Bouillet, Corinne; Kazatchkine, Michel; Bélec, Laurent

2008-01-20

56

Human Immunodeficiency Virus Type 1 Subtype B Ancestral Envelope Protein Is Functional and Elicits Neutralizing Antibodies in Rabbits Similar to Those Elicited by a Circulating Subtype B Envelope  

PubMed Central

Human immunodeficiency virus type 1 (HIV-1) is a difficult target for vaccine development, in part because of its ever-expanding genetic diversity and attendant capacity to escape immunologic recognition. Vaccine efficacy might be improved by maximizing immunogen antigenic similarity to viruses likely to be encountered by vaccinees. To this end, we designed a prototype HIV-1 envelope vaccine using a deduced ancestral state for the env gene. The ancestral state reconstruction method was shown to be >95% accurate by computer simulation and 99.8% accurate when estimating the known inoculum used in an experimental infection study in rhesus macaques. Furthermore, the deduced ancestor gene differed from the set of sequences used to derive the ancestor by an average of 12.3%, while these latter sequences were an average of 17.3% different from each other. A full-length ancestral subtype B HIV-1 env gene was constructed and shown to produce a glycoprotein of 160 kDa that bound and fused with cells expressing the HIV-1 coreceptor CCR5. This Env was also functional in a virus pseudotype assay. When either gp160- or gp140-expressing plasmids and recombinant gp120 were used to immunize rabbits in a DNA prime-protein boost regimen, the artificial gene induced immunoglobulin G antibodies capable of weakly neutralizing heterologous primary HIV-1 strains. The results were similar for rabbits immunized in parallel with a natural isolate, HIV-1 SF162. Further design efforts to better present conserved neutralization determinants are warranted. PMID:16103173

Doria-Rose, N. A.; Learn, G. H.; Rodrigo, A. G.; Nickle, D. C.; Li, F.; Mahalanabis, M.; Hensel, M. T.; McLaughlin, S.; Edmonson, P. F.; Montefiori, D.; Barnett, S. W.; Haigwood, N. L.; Mullins, J. I.

2005-01-01

57

Potent and synergistic neutralization of human immunodeficiency virus (HIV) type 1 primary isolates by hyperimmune anti-HIV immunoglobulin combined with monoclonal antibodies 2F5 and 2G12.  

PubMed Central

Three antibody reagents that neutralize primary human immunodeficiency virus type 1 (HIV-1) isolates were tested for magnitude and breadth of neutralization when used alone or in double or triple combinations. Hyperimmune anti-HIV immunoglobulin (HIVIG) is derived from the plasma of HIV-1-infected donors, and monoclonal antibodies (MAbs) 2F5 and 2G12 bind to distinct regions of the HIV-1 envelope glycoprotein. The antibodies were initially tested against a panel of 15 clade B HIV-1 isolates, using a single concentration that is achievable in vivo (HIVIG, 2,500 microg/ml; MAbs, 25 microg/ml). Individual antibody reagents neutralized many of the viruses tested, but antibody potency varied substantially among the viruses. The virus neutralization produced by double combinations of HIVIG plus 2F5 or 2G12, the two MAbs together, or the triple combination of HIVIG, 2F5, and 2G12 was generally equal to or greater than that predicted by the effect of individual antibodies. Overall, the triple combination displayed the greatest magnitude and breadth of neutralization. Synergistic neutralization was evaluated by analyzing data from dose-response curves of each individual antibody reagent compared to the triple combination and was demonstrated against each of four viruses tested. Therefore, combinations of polyclonal and monoclonal anti-HIV antibodies can produce additive or synergistic neutralization of primary HIV-1 isolates. Passive immunotherapy for treatment or prophylaxis of HIV-1 should consider mixtures of potent neutralizing antibody reagents to expand the magnitude and breadth of virus neutralization. PMID:9311792

Mascola, J R; Louder, M K; VanCott, T C; Sapan, C V; Lambert, J S; Muenz, L R; Bunow, B; Birx, D L; Robb, M L

1997-01-01

58

Analysis and validation of the phosphorylated metabolites of two anti-human immunodeficiency virus nucleotides (stavudine and didanosine) by pressure-assisted CE-ESI-MS/MS in cell extracts: sensitivity enhancement by the use of perfluorinated acids and alcohols as coaxial sheath-liquid make-up constituents.  

PubMed

A CE method utilizing triple quadrupole electrospray (ES) MS (MS/MS) detection was developed and validated for the simultaneous measurement of nucleoside 5'-triphosphate and 5'-monophosphate anabolites of the anti-HIV (human immunodeficiency virus) didanosine (ddAMP, ddATP) and stavudine (d4TMP, d4TTP), among a pool of 14 endogenous 5'-mono-, di-, and triphosphate nucleosides. These compounds were spiked and extracted from peripheral blood mononuclear cells (PBMCs) which are the sites of HIV replication and drug action. An acetic acid/ammonia buffer (pH 10, ionic strength of 40 mM) was selected as running electrolyte, and the separation was performed by the simultaneous application of a CE voltage of +30 kV and an overimposed pressure of 28 mbar (0.4 psi). The application of pressure assistance was needed to provide stable ES conditions for successful coupling. The coupling was carried out with a modified sheath-flow interface, with one uninterrupted capillary (80 cmx 50 microm id; 192 microm od) in a dimension that fits into the ESI needle to get a stable ion spray. Some CE-MS parameters such as overimposed pressure, sheath-liquid composition, sheath-liquid and sheath-gas flow rates, ES voltage, and the CE capillary position were optimized in order to obtain an optimal sensitivity. The use of perfluorinated alcohols and acids in the coaxial sheath-liquid make-up (2,2,2-trifluoroethanol + 0.2 mM tridecafluoroheptanoic acid) appeared to provide the best MS sensitivity and improve the stability of spray. The linearity of the CE-MS and CE-MS/MS methods was checked under these conditions. Validation parameters such as accuracy, intraday and interday precision, and LOQs were determined in CE-MS/MS mode. Finally, the quantitation of d4T-TP and ddA-TP was validated in this CE-MS/MS system. PMID:16786481

Bezy, Vincent; Chaimbault, Patrick; Morin, Philippe; Unger, Steve E; Bernard, Marie-Charlotte; Agrofoglio, Luigi A

2006-06-01

59

Limited Contribution of Mucosal IgA to Simian Immunodeficiency Virus (SIV)-Specific Neutralizing Antibody Response and Virus Envelope Evolution in Breast Milk of SIV-Infected, Lactating Rhesus Monkeys?  

PubMed Central

Breast milk transmission of human immunodeficiency virus (HIV) remains an important mode of infant HIV acquisition. Interestingly, the majority of infants remain uninfected during prolonged virus exposure via breastfeeding, raising the possibility that immune components in milk prevent mucosal virus transmission. HIV-specific antibody responses are detectable in the milk of HIV-infected women and simian immunodeficiency virus (SIV)-infected monkeys; however, the role of these humoral responses in virus neutralization and local virus quasispecies evolution has not been characterized. In this study, four lactating rhesus monkeys were inoculated with SIVmac251 and monitored for SIV envelope-specific humoral responses and virus evolution in milk and plasma throughout infection. While the kinetics and breadth of the SIV-specific IgG and IgA responses in milk were similar to those in plasma, the magnitude of the milk responses was considerably lower than that of the plasma responses. Furthermore, a neutralizing antibody response against the inoculation virus was not detected in milk samples at 1 year after infection, despite a measurable autologous neutralizing antibody response in plasma samples obtained from three of four monkeys. Interestingly, while IgA is the predominant immunoglobulin in milk, the milk SIV envelope-specific IgA response was lower in magnitude and demonstrated more limited neutralizing capacity against a T-cell line-adapted SIV compared to those of the milk IgG response. Finally, amino acid mutations in the envelope gene product of SIV variants in milk and plasma samples occurred in similar numbers and at similar positions, indicating that the humoral immune pressure in milk does not drive distinct virus evolution in the breast milk compartment. PMID:21041730

Permar, Sallie R.; Wilks, Andrew B.; Ehlinger, Elizabeth P.; Kang, Helen H.; Mahlokozera, Tatenda; Coffey, Rory T.; Carville, Angela; Letvin, Norman L.; Seaman, Michael S.

2011-01-01

60

Human immunodeficiency virus (HIV)-infected cells and free virus directly activate the classical complement pathway in rabbit, mouse and guinea-pig sera; activation results in virus neutralization by virolysis.  

PubMed Central

Since animal models of human immunodeficiency virus (HIV) infection are being used increasingly in determining various aspects of virus/host interaction and as models for virus expression, it will be important to assess any significant differences in anti-viral immune responses between animals and humans. Previous studies have shown that incubation of HIV with non-immune sera from several animal species results in virus neutralization, and that rabbit serum can lyse HIV-infected cells. The objectives of the current study were to evaluate the animal complement pathway(s) activated by HIV and HIV-infected cells and determine the mechanism by which complement could mediate viral neutralization. Incubation of HIV-infected cells with mouse, guinea-pig or rabbit sera resulted in cell-surface deposition of C3 fragments. Deposition of C3 fragments did not occur either in the presence of C4-deficient guinea-pig serum or in the absence of Ca2+, indicating that activation by infected cells occurred via the classical pathway. Neutralization of free virus was also mediated by the classical pathway since C4-deficient guinea-pig serum and Ca(2+)-chelated sera lacked activity. Serum treatment of virus resulted in release of HIV reverse transcriptase (RT), suggesting that neutralization occurred by C5b-9-mediated virolysis. RT was also released from simian immunodeficiency virus by animal complement. Antibodies in animal sera were not responsible for the classical pathway activation by free virus or HIV-infected cells. These results define several substantial differences between animal and human complement reactivity with HIV which could significantly affect the ability of HIV to replicate in animals, and which need to be considered in the assessment of animal models of HIV infection. PMID:1916889

Spear, G T; Sullivan, B L; Takefman, D M; Landay, A L; Lint, T F

1991-01-01

61

Immunodeficiency disorders  

MedlinePLUS

... HIV in their immune systems and improve their immunity. Patients who are going to have a planned ... be used to treat certain immunodeficiency conditions. Passive immunity (receiving antibodies produced by another person or animal) ...

62

Identification of 81LGxGxxIxW89 and 171EDRW174 Domains from Human Immunodeficiency Virus Type 1 Vif That Regulate APOBEC3G and APOBEC3F Neutralizing Activity?  

PubMed Central

The human cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F) potently restrict human immunodeficiency virus type 1 (HIV-1) replication, but they are neutralized by the viral protein Vif. Vif bridges A3G and A3F with a Cullin 5 (Cul5)-based E3 ubiquitin ligase and mediates their proteasomal degradation. This mechanism has been extensively studied, and several Vif domains have been identified that are critical for A3G and A3F neutralization. Here, we identified two additional domains. Via sequence analysis of more than 2,000 different HIV-1 Vif proteins, we identified two highly conserved amino acid sequences, 81LGxGxSIEW89 and 171EDRWN175. Within the 81LGxGxSIEW89 sequence, residues L81, G82, G84, and, to a lesser extent, I87 and W89 play very critical roles in A3G/A3F neutralization. In particular, residues L81 and G82 determine Vif binding to A3F, residue G84 determines Vif binding to both A3G and A3F, and residues 86SIEW89 affect Vif binding to A3F, A3G, and Cul5. Accordingly, this 81LGxGxSIEW89 sequence was designated the 81LGxGxxIxW89 domain. Within the 171EDRWN175 sequence, all residues except N175 are almost equally important for regulation of A3F neutralization, and consistently, they determine Vif binding only to A3F. Accordingly, this domain was designated 171EDRW174. The LGxGxxIxW domain is also partially conserved in simian immunodeficiency virus Vif from rhesus macaques (SIVmac239) and has a similar activity. Thus, 81LGxGxxIxW89 and 171EDRW174 are two novel functional domains that are very critical for Vif function. They could become new targets for inhibition of Vif activity during HIV replication. PMID:20335268

Dang, Ying; Davis, Roderick W.; York, Ian A.; Zheng, Yong-Hui

2010-01-01

63

Scorpion-Toxin Mimics of CD4 in Complex with Human Immunodeficiency Virus gp120: Crystal Structures, Molecular Mimicry, and Neutralization Breadth  

SciTech Connect

The binding surface on CD4 for the HIV-1 gp120 envelope glycoprotein has been transplanted previously onto a scorpion-toxin scaffold. Here, we use X-ray crystallography to characterize atomic-level details of gp120 with this transplant, CD4M33. Despite known envelope flexibility, the conformation of gp120 induced by CD4M33 was so similar to that induced by CD4 that localized measures were required to distinguish ligand-induced differences from lattice variation. To investigate relationships between structure, function, and mimicry, an F23 analog of CD4M33 was devised. Structural and thermodynamic analyses showed F23 to be a better molecular mimic of CD4 than CD4M33. F23 also showed increased neutralization breadth, against diverse isolates of HIV-1, HIV-2, and SIVcpz. Our results lend insight into the stability of the CD4 bound conformation of gp120, define measures that quantify molecular mimicry as a function of evolutionary distance, and suggest how such evaluations might be useful in developing mimetic antagonists with increased neutralization breadth.

Huang, Chih-chin; Stricher, Francois; Martin, Loic; Decker, Julie M.; Majeed, Shahzad; Barthe, Phillippe; Hendrickson, Wayne A.; Robinson, James; Roumestand, Christian; Sodroski, Joseph; Wyatt, Richard; Shaw, George M.; Vita, Claudio; Kwong, Peter D. (Havard-Med); (NIH); (UAB); (Columbia); (CEA Saclay); (Tulane); (Faculty of Pharmacy)

2010-07-19

64

Protection against High-Dose Highly Pathogenic Mucosal SIV Challenge at Very Low Serum Neutralizing Titers of the Antibody-Like Molecule CD4-IgG2  

PubMed Central

Passive transfer studies using monoclonal or polyclonal antibodies in the macaque model have been valuable for determining conditions for antibody protection against immunodeficiency virus challenge. Most studies have employed hybrid simian/human immunodeficiency virus (SHIV) challenge in conjunction with neutralizing human monoclonal antibodies. Passive protection against SIV, particularly the pathogenic prototype virus SIVmac239, has been little studied because of the paucity of neutralizing antibodies to this virus. Here, we show that the antibody-like molecule CD4-IgG2 potently neutralizes SIVmac239 in vitro. When administered by an osmotic pump to maintain concentrations given the short half-life of CD4-IgG2 in macaques, the molecule provided sterilizing immunity/protection against high-dose mucosal viral challenge to a high proportion of animals (5/7 at a 200 mg dose CD4-IgG2 and 3/6 at a 20 mg dose) at serum concentrations below 1.5 µg/ml. The neutralizing titers of such sera were predicted to be very low and indeed sera at a 1?4 dilution produced no neutralization in a pseudovirus assay. Macaque anti-human CD4 titers did develop weakly at later time points in some animals but were not associated with the level of protection against viral challenge. The results show that, although SIVmac239 is considered a highly pathogenic virus for which vaccine-induced T cell responses in particular have provided limited benefit against high dose challenge, the antibody-like CD4-IgG2 molecule at surprisingly low serum concentration affords sterilizing immunity/protection to a majority of animals. PMID:22848744

Poignard, Pascal; Moldt, Brian; Maloveste, Karla; Campos, Noëlie; Olson, William C.; Rakasz, Eva; Watkins, David I.; Burton, Dennis R.

2012-01-01

65

Polysaccharopeptide from Coriolus versicolor has potential for use against human immunodeficiency virus type 1 infection  

Microsoft Academic Search

Polysaccharopeptide (PSP) isolated from the edible mushroom Coriolus versicolor was tested for its potential as an anti-human immunodeficiency virus type 1 (HIV-1) compound in a series of in vitro assays. It demonstrated inhibition of the interaction between HIV-1 gp120 and immobilized CD4 receptor (IC50 = 150?gml), potent inhibition of recombinant HIV-1 reverse transcriptase (IC50 = 6.25?gml), and inhibited a glycohydrolase

Richard A. Collins; Tzi Bun Ng

1997-01-01

66

Sensitivity of human immunodeficiency virus infection to various a, b and c chemokines  

Microsoft Academic Search

Examination of a large panel of chemokines indi- cates that in addition to RANTES, MIP-1a and MIP- 1b, the b-chemokine MCP-2 and, to a lesser extent, the c-chemokine lymphotactin also show anti- human immunodeficiency virus (HIV) activity in cell culture. The amount of chemokine needed to sup- press HIV replication by Z 50% was generally greater (Z 250 ng\\/ml) than

Giampaolo Greco; Carl Mackewicz; Jay A. Levy

67

Structure-Based Design of a Protein Immunogen that Displays an HIV-1 gp41 Neutralizing Epitope  

SciTech Connect

Antibody Z13e1 is a relatively broadly neutralizing anti-human immunodeficiency virus type 1 antibody that recognizes the membrane-proximal external region (MPER) of the human immunodeficiency virus type 1 envelope glycoprotein gp41. Based on the crystal structure of an MPER epitope peptide in complex with Z13e1 Fab, we identified an unrelated protein, interleukin (IL)-22, with a surface-exposed region that is structurally homologous in its backbone to the gp41 Z13e1 epitope. By grafting the gp41 Z13e1 epitope sequence onto the structurally homologous region in IL-22, we engineered a novel protein (Z13-IL22-2) that contains the MPER epitope sequence for use as a potential immunogen and as a reagent for the detection of Z13e1-like antibodies. The Z13-IL22-2 protein binds Fab Z13e1 with a K{sub d} of 73 nM. The crystal structure of Z13-IL22-2 in complex with Fab Z13e1 shows that the epitope region is faithfully replicated in the Fab-bound scaffold protein; however, isothermal calorimetry studies indicate that Fab binding to Z13-IL22-2 is not a lock-and-key event, leaving open the question of whether conformational changes upon binding occur in the Fab, in Z13-IL-22, or in both.

Stanfield, Robyn L.; Julien, Jean-Philippe; Pejchal, Robert; Gach, Johannes S.; Zwick, Michael B.; Wilson, Ian A. (Scripps)

2012-06-27

68

Novel Inhibitory Effects of g-Glutamylcysteine Ethyl Ester against Human Immunodeficiency Virus Type 1 Production and Propagation  

Microsoft Academic Search

The anti-human immunodeficiency virus type I (anti-HIV-1) effects of g-glutamylcysteine ethyl ester (g-GCE; TEI-2306) were examined in vitro. In initial studies using a vigorously HIV-1-producing human T-lymphocytic cell line, g-GCE displayed a novel biphasic repressive effect on chronic HIV-1 infection that was unlike that of other glutathione prodrugs or other reported antioxidants. In high doses, up to a concentration of

SATOSHI KUBOTA; SHUBHRA SHETTY; HUIZHONG ZHANG; SHIGEHISA KITAHARA; ROGER J. POMERANTZ

1998-01-01

69

Common variable immunodeficiency.  

PubMed

Common variable immunodeficiency (CVI) is a heterogeneous immunodeficiency syndrome characterized by hypogammaglobulinemia, recurrent bacterial infections, and a variety of immunological abnormalities. In addition to recurrent infections, patients with this syndrome also suffer from an increased incidence of autoimmune disease and malignancy. Because the spectrum of associated diseases is broad, patients with CVI are seen by a variety of medical specialists. In this review, the pathogenesis, clinical manifestations, diagnosis, and treatment of CVI are discussed. PMID:11202479

Sneller, M C

2001-01-01

70

Disparate Actions of Hydroxyurea in Potentiation of Purine and Pyrimidine 2',3'-Dideoxynucleoside Activities Against Replication of Human Immunodeficiency Virus  

Microsoft Academic Search

We and other groups have recently reported the potentiation by ribonucleotide reductase inhibitors such as hydroxyurea of the anti-human immunodeficiency virus type 1 (HIV-1) activity of purine and pyrimidine 2',3'-dideoxynucleosides in both resting and phytohemagglutininstimulated peripheral blood mononuclear cells. Little agreement prevails, however, as to the mechanism of the synergistic effects described. We report here that in phytohemagglutininstimulated peripheral blood

Wen-Yi Gao; David G. Johns; Sudhichai Chokekijchai; Hiroaki Mitsuya

1995-01-01

71

Testing for Human Immunodeficiency Virus  

MedlinePLUS

... incisions made in the mother’s abdomen and uterus. Human Immunodeficiency Virus (HIV): A virus that attacks certain cells of the body’s immune system and causes acquired immunodeficiency syndrome (AIDS). Immune System: ...

72

Autoimmunity in Immunodeficiency  

PubMed Central

Primary immunodeficiencies (PID) comprise a diverse group of clinical disorders with varied genetic defects. Paradoxically, a substantial proportion of PID patients develop autoimmune phenomena in addition to having increased susceptibility to infections from their impaired immunity. Although much of our understanding comes from data gathered through experimental models, there are several well-characterized PID that have improved our knowledge of the pathways that drive autoimmunity. The goals of this review will be to discuss these immunodeficiencies and to review the literature with respect to the proposed mechanisms for autoimmunity within each put forth to date. PMID:23591608

Todoric, Krista; Koontz, Jessica B.; Mattox, Daniel; Tarrant, Teresa K.

2013-01-01

73

Primary immunodeficiencies: 2009 update  

PubMed Central

More than 50 years after Ogdeon Bruton’s discovery of congenital agammaglobulinemia, human primary immunodeficiencies (PIDs) continue to unravel novel molecular and cellular mechanisms that govern development and function of the human immune system. This report provides the updated classification of PIDs, that has been compiled by the International Union of Immunological Societies (IUIS) Expert Committee of Primary Immunodeficiencies after its biannual meeting, in Dublin (Ireland) in June 2009. Since the appearance of the last classification in 2007, novel forms of PID have been discovered, and additional pathophysiology mechanisms that account for PID in humans have been unraveled. Careful analysis and prompt recognition of these disorders is essential to prompt effective forms of treatment and thus to improve survival and quality of life in patients affected with PIDs. PMID:20004777

Notarangelo, Luigi D.; Fischer, Alain; Geha, Raif. S.; Casanova, Jean-Laurent; Chapel, Helen; Conley, Mary Ellen; Cunningham-Rundles, Charlotte; Etzioni, Amos; Hammartröm, Lennart; Nonoyama, Shigeaki; Ochs, Hans D.; Puck, Jennifer; Roifman, Chaim; Seger, Reinhard; Wedgwood, Josiah

2009-01-01

74

Characterization of a DNA vaccine expressing a human immunodeficiency virus-like particle  

Microsoft Academic Search

An ideal human immunodeficiency virus type-1 (HIV-1) vaccine will most likely need to elicit cross-reactive neutralizing antibodies and a strong cell-mediated immune response against multiple HIV-1 antigens to confer protection against challenge. In this study, DNA vaccines were constructed to express virally regulated human immunodeficiency virus-like particles (VLP) to elicit broad-spectrum immune responses to multiple HIV-1 antigens. VLPs were efficiently

Kelly R. Young; James M. Smith; Ted M. Ross

2004-01-01

75

Humoral immune response to the entire human immunodeficiency virus envelope glycoprotein made in insect cells  

SciTech Connect

The human immunodeficiency virus envelope gene was expressed in insect cells by using a Baculovirus expression vector. The protein has an apparent molecular mass of 160 kDa, appears on the surface of infected insect cells, and does not appear to be cleaved to glycoproteins gp120 and gp41. Goats immunized with the 160-kDa protein have high titers of antibody that neutralizes virus infection as measured by viral gene expression or cell cytolysis. In addition, immune sera can block fusion of human immunodeficiency virus-infected cells in culture. Both neutralization and fusion-blocking activities are bound to and eluted from immobilized gp120.

Rusche, J.R.; Lynn, D.L.; Robert-Guroff, M.; Langlois, A.J.; Lyerly, H.K.; Carson, H.; Krohn, K.; Ranki, A.; Gallo, R.C.; Bolognesi, D.P.; Putney, S.D.

1987-10-01

76

Space Flight Immunodeficiency  

NASA Technical Reports Server (NTRS)

The National Aeronautics and Space Administration (NASA) has had sufficient concern for the well-being of astronauts traveling in space to create the National Space Biomedical Research Institute (NSBRI), which is investigating several areas of biomedical research including those of immunology. As part of the Immunology, Infection, and Hematology Team, the co-investigators of the Space Flight Immunodeficiency Project began their research projects on April 1, 1998 and are now just into the second year of work. Two areas of research have been targeted: 1) specific immune (especially antibody) responses and 2) non-specific inflammation and adhesion. More precise knowledge of these two areas of research will help elucidate the potential harmful effects of space travel on the immune system, possibly sufficient to create a secondary state of immunodeficiency in astronauts. The results of these experiments are likely to lead to the delineation of functional alterations in antigen presentation, specific immune memory, cytokine regulation of immune responses, cell to cell interactions, and cell to endothelium interactions.

Shearer, William T.

1999-01-01

77

An anti-human ICAM-1 antibody inhibits rhinovirus-induced exacerbations of lung inflammation.  

PubMed

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ?90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo. PMID:23935498

Traub, Stephanie; Nikonova, Alexandra; Carruthers, Alan; Dunmore, Rebecca; Vousden, Katherine A; Gogsadze, Leila; Hao, Weidong; Zhu, Qing; Bernard, Katie; Zhu, Jie; Dymond, Michael; McLean, Gary R; Walton, Ross P; Glanville, Nicholas; Humbles, Alison; Khaitov, Musa; Wells, Ted; Kolbeck, Roland; Leishman, Andrew J; Sleeman, Matthew A; Bartlett, Nathan W; Johnston, Sebastian L

2013-01-01

78

Immunodeficiency in methylmalonic acidaemia.  

PubMed

Three Chinese infants with methylmalonic acidaemia were described. They presented in the neonatal period with recurrent episodes of poor feeding, lethargy, apnoea and severe acidosis. The diagnosis was established by increased methylmalonic acid concentration in the plasma and/or urine. Pancytopenia was a prominent feature in all three patients. Only patient three had assessment of lymphocyte subsets and it showed diminished population of B-lymphocytes and a reversed CD4/CD8 ratio. All three patients were unresponsive to vitamin B12. They experienced severe infections including Gram-negative septicaemia, candidiasis and Pneumocystis carinii pneumonia which caused their deaths. Patients with this disease should be regarded as having severe immunodeficiency, and in addition to optimal metabolic control, they should be treated aggressively for any suspected infective episodes. PMID:1562372

Wong, S N; Low, L C; Lau, Y L; Nicholls, J; Chan, M Y

1992-04-01

79

Human immunodeficiency virus endocrinopathy  

PubMed Central

Human immunodeficiency virus (HIV) endocrinopathy encompasses a broad spectrum of disorders. Almost all the endocrine organs are virtually affected by HIV infection. HIV can directly alter glandular function. More commonly secondary endocrine dysfunction occurs due to opportunistic infections and neoplasms in immunocompromised state. The complex interaction between HIV infection and endocrine system may be manifested as subtle biochemical and hormonal perturbation to overt glandular failure. Antiretroviral therapy as well as other essential medications often result in adverse endocrinal consequences. Apart from adrenal insufficiency, hypogonadism, diabetes and bone loss, AIDS wasting syndrome and HIV lipodystrophy need special reference. Endocrinal evaluation should proceed as in other patients with suspected endocrine dysfunction. Available treatment options have been shown to improve quality of life and long-term mortality in AIDS patients. PMID:22028995

Sinha, Uma; Sengupta, Nilanjan; Mukhopadhyay, Prasanta; Roy, Keshab Sinha

2011-01-01

80

Recurrent Infections May Signal Immunodeficiencies  

MedlinePLUS

... for reaching a diagnosis and developing an effective treatment plan. The most common forms of immunodeficiency are often treated with infusions of antibodies called intravenous immunoglobulins (IVIG). IVIG replaces the antibodies that your body is ...

81

Characteristics of polyclonal anti-human nephrin antibodies induced by genetic immunization using nephrin cDNA  

Microsoft Academic Search

Background. Nephrin is an essential protein for maintaining the normal structure of the podocyte foot process and the glomerular filtration barrier. To analyse the mechanism of proteinuria and treat- ment of nephrotic syndrome, we produced and characterized polyclonal anti-human nephrin anti- bodies using a newly developed genetic immunization technique. Methods. An expression vector with full-length or fragmented cDNA of human

Togo Aoyama; Kouju Kamata; Nozomu Yamanaka; Yasuo Takeuchi; Masaaki Higashihara; Seishi Kato

2006-01-01

82

Optical Imaging of the Adoptive Transfer of Human Endothelial Cells in Mice Using Anti-Human CD31 Monoclonal Antibody  

PubMed Central

Purpose The development of endothelium-specific imaging agents capable of specific binding to human cells under the conditions of flow for the needs of regenerative medicine and cancer research. The goal of the study was testing the feasibility of optical imaging of human endothelial cells implanted in mice. Methods Mouse model of adoptive human endothelial cell transfer was obtained by implanting cells in Matrigel matrix in subcutaneous space (Kang, Torres, Wald, Weissleder, and Bogdanov, Jr., Targeted imaging of human endothelial-specific marker in a model of adoptive cell transfer. Lab. Invest. 86: 599-609, 2006). Several endothelium-specific proteins were labeled with near-infrared fluorochrome (Cy5.5) and tested in vitro. Fluorescence imaging using anti-human CD31 antibody was performed in vivo. The obtained results were corroborated by using fluorescence microscopy of tissue sections. Results We determined that monoclonal anti-human CD31 antibodies labeled with Cy5.5 were efficiently binding to human endothelial cells and were not subject to rapid endocytosis. We further demonstrated that specific near-infrared optical imaging signal was present only in Matrigel implants seeded with human endothelium cells and was absent from control Matrigel implants. Histology showed staining of cells lining vessels and revealed the formation of branched networks of CD31-positive cells. Conclusions Anti-human CD31 antibodies tagged with near-infrared fluorochromes can be used for detection of perfused blood vessels harboring human endothelial cells in animal models of adoptive transfer. PMID:17373582

Bogdanov, Alexei A.; Lin, Charles P.; Kang, Hye-Won

2009-01-01

83

Screening of anti-human leukocyte monoclonal antibodies for reactivity with equine leukocytes.  

PubMed

Three hundred and seventy-nine monoclonal antibodies (mAbs) against various human CD molecules supplied to the HLDA8 animal homologues section (including four isotype controls) were analysed for cross-reactivity with equine leukocytes. First, flow cytometric identification of positively reacting mAbs was performed in one laboratory. Thereafter, a second round of flow cytometric evaluation was performed, involving three laboratories participating in the study. The first test-round indicated 17 mAbs as potentially positive. After the second round of flow cytometric analysis, 14 mAbs remained (directed against CD2, CD11a, CD18, CD44, CD45, CD49d, CD91, CD163 and CD172) where cross-reactivity was anticipated based on similarities between the human and equine staining pattern. Additionally, there was 1 mAb with weak likely positive reactivity, 12 mAbs with positive staining, which likely do not reflect valuable data, 5 mAbs with clear alternate expression pattern from that expected from humans, 5 mAbs with a questionable staining pattern itself, i.e. that was variable between the three labs, 32 mAbs with weak-positive expression and alternate staining pattern, and 279 negative mAbs (including the four isotype controls) were detected. In 31 cases, more appropriate target cells, such as thymocytes or stem cells, were not available for the screening. The results underline the value of this "cross-reactivity" approach for equine immunology. However, as only a few mAbs against leukocyte surface antigens reacted positively (approximately 4% of the mAbs submitted), the analysis of further anti-human mAbs and directed efforts to develop species-specific anti-CD mAb are still required. PMID:17707518

Ibrahim, Sherif; Saunders, Kelly; Kydd, Julia H; Lunn, D Paul; Steinbach, Falko

2007-09-15

84

Screening for Human Immunodeficiency Virus (HIV)  

MedlinePLUS

... FINAL | 1 Understanding Task Force Recommendations Screening for Human Immunodeficiency Virus (HIV) The U.S. Preventive Services Task ... transmit the virus to her baby. Facts About Human Immunodeficiency Virus (HIV) Infection Nearly 1.2 million ...

85

Human immunodeficiency virus infection and pneumothorax.  

PubMed

Pneumothorax is a serious and relatively frequent complication of human immunodeficiency virus (HIV) infection that may associate with increased morbidity and mortality and may prove difficult to manage, especially in patients with acquired immunodeficiency syndrome (AIDS). PMID:25337392

Terzi, Eirini; Zarogoulidis, Konstantinos; Kougioumtzi, Ioanna; Dryllis, Georgios; Kioumis, Ioannis; Pitsiou, Georgia; Machairiotis, Nikolaos; Katsikogiannis, Nikolaos; Tsiouda, Theodora; Madesis, Athanasios; Karaiskos, Theodoros; Zarogoulidis, Paul

2014-10-01

86

Human immunodeficiency virus infection and pneumothorax  

PubMed Central

Pneumothorax is a serious and relatively frequent complication of human immunodeficiency virus (HIV) infection that may associate with increased morbidity and mortality and may prove difficult to manage, especially in patients with acquired immunodeficiency syndrome (AIDS). PMID:25337392

Terzi, Eirini; Zarogoulidis, Konstantinos; Kougioumtzi, Ioanna; Dryllis, Georgios; Kioumis, Ioannis; Pitsiou, Georgia; Machairiotis, Nikolaos; Katsikogiannis, Nikolaos; Tsiouda, Theodora; Madesis, Athanasios; Karaiskos, Theodoros

2014-01-01

87

Actin cytoskeletal defects in immunodeficiency  

PubMed Central

The importance of the cytoskeleton in mounting a successful immune response is evident from the wide range of defects that occur in actin-related primary immunodeficiencies (PIDs). Studies of these PIDs have revealed a pivotal role for the actin cytoskeleton in almost all stages of immune system function, from hematopoiesis and immune cell development, through to recruitment, migration, intercellular and intracellular signaling, and activation of both innate and adaptive immune responses. The major focus of this review is the immune defects that result from mutations in the Wiskott-Aldrich syndrome gene (WAS), which have a broad impact on many different processes and give rise to clinically heterogeneous immunodeficiencies. We also discuss other related genetic defects and the possibility of identifying new genetic causes of cytoskeletal immunodeficiency. PMID:24117828

Moulding, Dale A; Record, Julien; Malinova, Dessislava; Thrasher, Adrian J

2013-01-01

88

Laboratory evaluation of primary immunodeficiencies  

PubMed Central

Primary immunodeficiencies are congenital disorders caused by defects in different elements of the immune system. Affected patients usually present clinically with recurrent infections, severe infections, or both, as well as autoimmune phenomena that are associated with many of these disorders. Early diagnosis is essential for referral to specialized care centers and the prompt initiation of appropriate therapy. In this article the authors describe a general approach for the investigation of the most common primary immunodeficiencies, outlining the typical clinical symptoms and most appropriate laboratory investigations. PMID:20042230

Oliveira, João B.; Fleisher, Thomas A.

2012-01-01

89

Primary immunodeficiencies underlying fungal infections  

PubMed Central

Purpose of review We review the primary immunodeficiencies underlying an increasing variety of superficial and invasive fungal infections. We also stress that the occurrence of such fungal infections should lead physicians to search for the corresponding single-gene inborn errors of immunity. Finally, we suggest that other fungal infections may also result from hitherto unknown inborn errors of immunity, at least in some patients with no known risk factors. Recent findings An increasing number of primary immunodeficiencies are being shown to underlie fungal infectious diseases in children and young adults. Inborn errors of the phagocyte NADPH oxidase complex (chronic granulomatous disease), severe congenital neutropenia and leukocyte adhesion deficiency type I confer a predisposition to invasive aspergillosis and candidiasis. More rarely, inborn errors of IFN-? immunity underlie endemic mycoses. Inborn errors of IL-17 immunity have recently been shown to underlie chronic mucocutaneous candidiasis, whereas inborn errors of CARD9 immunity underlie deep dermatophytosis and invasive candidiasis. Summary Chronic mucocutaneous candidiasis, invasive candidiasis, invasive aspergillosis, deep dermatophytosis, pneumocystosis, and endemic mycoses can all be caused by primary immunodeficiencies. Each type of infection is highly suggestive of a specific type of primary immunodeficiency. In the absence of overt risk factors, single-gene inborn errors of immunity should be sought in children and young adults with these and other fungal diseases. PMID:24240293

Lanternier, Fanny; Cypowyj, Sophie; Picard, Capucine; Bustamante, Jacinta; Lortholary, Olivier; Casanova, Jean-Laurent; Puel, Anne

2014-01-01

90

Hematopoiesis and models of immunodeficiency  

Microsoft Academic Search

This review focuses on recessive mutations at three loci whose gene products play critical roles in the development and regulation of the murine immune system. These mutations are: severe combined immunodeficiency (scid), osteopetrosis (op), and motheaten (me). The scid mutation blocks differentiation of functional T and B lymphocytes and interferes with DNA repair processes in multiple cell lineages. The normal

L D Shultz

1991-01-01

91

Respiratory syncytial virus infections in infants affected by primary immunodeficiency.  

PubMed

Primary immunodeficiencies are rare inherited disorders that may lead to frequent and often severe acute respiratory infections. Respiratory syncytial virus (RSV) is one of the most frequent pathogens during early infancy and the infection is more severe in immunocompromised infants than in healthy infants, as a result of impaired T- and B-cell immune response unable to efficaciously neutralize viral replication, with subsequent increased viral shedding and potentially lethal lower respiratory tract infection. Several authors have reported a severe clinical course after RSV infections in infants and children with primary and acquired immunodeficiencies. Environmental prophylaxis is essential in order to reduce the infection during the epidemic season in hospitalized immunocompromised infants. Prophylaxis with palivizumab, a humanized monoclonal antibody against the RSV F protein, is currently recommended in high-risk infants born prematurely, with chronic lung disease or congenital heart disease. Currently however the prophylaxis is not routinely recommended in infants with primary immunodeficiency, although some authors propose the extension of prophylaxis to this high risk population. PMID:25089282

Lanari, Marcello; Vandini, Silvia; Capretti, Maria Grazia; Lazzarotto, Tiziana; Faldella, Giacomo

2014-01-01

92

Respiratory Syncytial Virus Infections in Infants Affected by Primary Immunodeficiency  

PubMed Central

Primary immunodeficiencies are rare inherited disorders that may lead to frequent and often severe acute respiratory infections. Respiratory syncytial virus (RSV) is one of the most frequent pathogens during early infancy and the infection is more severe in immunocompromised infants than in healthy infants, as a result of impaired T- and B-cell immune response unable to efficaciously neutralize viral replication, with subsequent increased viral shedding and potentially lethal lower respiratory tract infection. Several authors have reported a severe clinical course after RSV infections in infants and children with primary and acquired immunodeficiencies. Environmental prophylaxis is essential in order to reduce the infection during the epidemic season in hospitalized immunocompromised infants. Prophylaxis with palivizumab, a humanized monoclonal antibody against the RSV F protein, is currently recommended in high-risk infants born prematurely, with chronic lung disease or congenital heart disease. Currently however the prophylaxis is not routinely recommended in infants with primary immunodeficiency, although some authors propose the extension of prophylaxis to this high risk population. PMID:25089282

Capretti, Maria Grazia; Lazzarotto, Tiziana; Faldella, Giacomo

2014-01-01

93

Acquired immunodeficiency syndrome and human immunodeficiency virus infection in Nevada.  

PubMed Central

We summarize information from three sets of epidemiologic data: the Nevada AIDS [acquired immunodeficiency syndrome] Surveillance System, which contains information about every case identified within the state boundaries through September 1989; the human immunodeficiency virus (HIV) seroprevalence reporting systems, which currently include data on all HIV-positive reports submitted statewide to public health authorities; and surveys on the knowledge, attitudes, and behaviors of Nevadans concerning HIV-related disease. The Nevada State AIDS Task Force outlined major policy recommendations, nearly half of which concerned testing; only 2 dealt with preventing HIV transmission. Greater efforts should go into education, particularly directed toward groups at greatest risk of exposure to HIV, and to improve community-based care of infected persons. PMID:2024509

Jarvis, J. Q.; Semiatin, S. L.

1991-01-01

94

Inactivation of human immunodeficiency virus type 1 by porphyrins.  

PubMed

We have evaluated the anti-human immunodeficiency virus (HIV) activity of a series of natural and synthetic porphyrins to identify compounds that could potentially be used as microbicides to provide a defense against infection by sexually transmitted virus. For assays we used an epithelial HeLa-CD4 cell line with an integrated long terminal repeat-beta-galactosidase gene. For structure-activity analysis, we divided the porphyrins tested into three classes: (i) natural porphyrins, (ii) metallo-tetraphenylporphyrin tetrasulfonate (metallo-TPPS4) derivatives, and (iii) sulfonated tetra-arylporphyrin derivatives. None of the natural porphyrins studied reduced infection by more than 80% at a concentration of 5 micro g/ml in these assays. Some metal chelates of TPPS4 were more active, and a number of sulfonated tetra-aryl derivatives showed significantly higher activity. Some of the most active compounds were the sulfonated tetranaphthyl porphyrin (TNapPS), sulfonated tetra-anthracenyl porphyrin (TAnthPS), and sulfonated 2,6-difluoro-meso-tetraphenylporphine [TPP(2,6-F2)S] and its copper chelate [TPP(2,6-F2)S,Cu], which reduced infection by 99, 96, 94, and 96%, respectively. Our observations indicate that at least some of these compounds are virucidal, i.e., that they render the virus noninfectious. The active compounds were found to inhibit binding of the HIV type 1 gp120 to CD4 and also to completely inhibit the ability of Env proteins expressed from recombinant vectors to induce cell fusion with receptor-bearing target cells. These results support the conclusion that modified porphyrins exhibit substantial activity against HIV and that their target is the HIV Env protein. PMID:12435696

Vzorov, Andrei N; Dixon, Dabney W; Trommel, Jenna S; Marzilli, Luigi G; Compans, Richard W

2002-12-01

95

Inactivation of Human Immunodeficiency Virus Type 1 by Porphyrins  

PubMed Central

We have evaluated the anti-human immunodeficiency virus (HIV) activity of a series of natural and synthetic porphyrins to identify compounds that could potentially be used as microbicides to provide a defense against infection by sexually transmitted virus. For assays we used an epithelial HeLa-CD4 cell line with an integrated long terminal repeat-?-galactosidase gene. For structure-activity analysis, we divided the porphyrins tested into three classes: (i) natural porphyrins, (ii) metallo-tetraphenylporphyrin tetrasulfonate (metallo-TPPS4) derivatives, and (iii) sulfonated tetra-arylporphyrin derivatives. None of the natural porphyrins studied reduced infection by more than 80% at a concentration of 5 ?g/ml in these assays. Some metal chelates of TPPS4 were more active, and a number of sulfonated tetra-aryl derivatives showed significantly higher activity. Some of the most active compounds were the sulfonated tetranaphthyl porphyrin (TNapPS), sulfonated tetra-anthracenyl porphyrin (TAnthPS), and sulfonated 2,6-difluoro-meso-tetraphenylporphine [TPP(2,6-F2)S] and its copper chelate [TPP(2,6-F2)S,Cu], which reduced infection by 99, 96, 94, and 96%, respectively. Our observations indicate that at least some of these compounds are virucidal, i.e., that they render the virus noninfectious. The active compounds were found to inhibit binding of the HIV type 1 gp120 to CD4 and also to completely inhibit the ability of Env proteins expressed from recombinant vectors to induce cell fusion with receptor-bearing target cells. These results support the conclusion that modified porphyrins exhibit substantial activity against HIV and that their target is the HIV Env protein. PMID:12435696

Vzorov, Andrei N.; Dixon, Dabney W.; Trommel, Jenna S.; Marzilli, Luigi G.; Compans, Richard W.

2002-01-01

96

Evolution of a simian immunodeficiency virus pathogen.  

PubMed

Analysis of disease induction by simian immunodeficiency viruses (SIV) in macaques was initially hampered by a lack of molecularly defined pathogenic strains. The first molecularly cloned SIV strains inoculated into macaques, SIVmacBK28 and SIVmacBK44 (hereafter designated BK28 and BK44, respectively), were cases in point, since they failed to induce disease within 1 year postinoculation in any inoculated animal. Here we report the natural history of infection with BK28 and BK44 in inoculated rhesus macaques and efforts to increase the pathogenicity of BK28 through genetic manipulation and in vivo passage. BK44 infection resulted in no disease in four animals infected for more than 7 years, whereas BK28 induced disease in less than half of animals monitored for up to 7 years. Elongation of the BK28 transmembrane protein (TM) coding sequence truncated by prior passage in human cells marginally increased pathogenicity, with two of four animals dying in the third year and one dying in the seventh year of infection. Modification of the BK28 long terminal repeat to include four consensus nuclear factor SP1 and two consensus NF-kappaB binding sites enhanced early virus replication without augmenting pathogenicity. In contrast, in vivo passage of BK28 from the first animal to die from immunodeficiency disease (1.5 years after infection) resulted in a consistently pathogenic strain and a 50% survival time of about 1.3 years, thus corresponding to one of the most pathogenic SIV strains identified to date. To determine whether the diverse viral quasispecies that evolved during in vivo passage was required for pathogenicity or whether a more virulent virus variant had evolved, we generated a molecular clone composed of the 3' half of the viral genome derived from the in vivo-passaged virus (H824) fused with the 5' half of the BK28 genome. Kinetics of disease induction with this cloned virus (BK28/H824) were similar to those with the in vivo-passaged virus, with four of five animals surviving less than 1.7 years. Thus, evolution of variants with enhanced pathogenicity can account for the increased pathogenicity of this SIV strain. The genetic changes responsible for this virulent transformation included at most 59 point mutations and 3 length-change mutations. The critical mutations were likely to have been multiple and dispersed, including elongation of the TM and Nef coding sequences; changes in RNA splice donor and acceptor sites, TATA box sites, and Sp1 sites; multiple changes in the V2 region of SU, including a consensus neutralization epitope; and five new N-linked glycosylation sites in SU. PMID:9420239

Edmonson, P; Murphey-Corb, M; Martin, L N; Delahunty, C; Heeney, J; Kornfeld, H; Donahue, P R; Learn, G H; Hood, L; Mullins, J I

1998-01-01

97

Human Immunodeficiency Virus (HIV) Primary Infection  

MedlinePLUS

newsletter | contact Share | Human Immunodeficiency Virus (HIV) Primary Infection Information for adults A A A When HIV is first contracted, there may be ... 1–6 weeks following exposure to HIV (the human immunodeficiency virus). Chronic infection with this virus can ...

98

Severe Viral Infections and Primary Immunodeficiencies  

PubMed Central

Patients with severe viral infections are often not thoroughly evaluated for immunodeficiencies. In this review, we summarize primary immunodeficiencies that predispose individuals to severe viral infections. Some immunodeficiencies enhance susceptibility to disease with a specific virus or family of viruses, whereas others predispose to diseases with multiple viruses in addition to disease with other microbes. Although the role of cytotoxic T cells in controlling viral infections is well known, a number of immunodeficiencies that predispose to severe viral diseases have recently been ascribed to defects in the Toll-like receptor–interferon signaling pathway. These immunodeficiencies are rare, but it is important to identify them both for prognostic information and for genetic counseling. Undoubtedly, additional mutations in proteins in the innate and adaptive arms of the immune system will be identified in the future, which will reveal the importance of these proteins in controlling infections caused by viruses and other pathogens. PMID:21960712

Cohen, Jeffrey I.

2011-01-01

99

Pathogenesis of human immunodeficiency virus infection.  

PubMed Central

The lentivirus human immunodeficiency virus (HIV) causes AIDS by interacting with a large number of different cells in the body and escaping the host immune response against it. HIV is transmitted primarily through blood and genital fluids and to newborn infants from infected mothers. The steps occurring in infection involve an interaction of HIV not only with the CD4 molecule on cells but also with other cellular receptors recently identified. Virus-cell fusion and HIV entry subsequently take place. Following virus infection, a variety of intracellular mechanisms determine the relative expression of viral regulatory and accessory genes leading to productive or latent infection. With CD4+ lymphocytes, HIV replication can cause syncytium formation and cell death; with other cells, such as macrophages, persistent infection can occur, creating reservoirs for the virus in many cells and tissues. HIV strains are highly heterogeneous, and certain biologic and serologic properties determined by specific genetic sequences can be linked to pathogenic pathways and resistance to the immune response. The host reaction against HIV, through neutralizing antibodies and particularly through strong cellular immune responses, can keep the virus suppressed for many years. Long-term survival appears to involve infection with a relatively low-virulence strain that remains sensitive to the immune response, particularly to control by CD8+ cell antiviral activity. Several therapeutic approaches have been attempted, and others are under investigation. Vaccine development has provided some encouraging results, but the observations indicate the major challenge of preventing infection by HIV. Ongoing research is necessary to find a solution to this devastating worldwide epidemic. Images PMID:8464405

Levy, J A

1993-01-01

100

Common variable immunodeficiency - an update  

PubMed Central

Common variable immunodeficiency (CVID) describes a heterogeneous subset of hypogammaglobulinemias of unknown etiology. Typically, patients present with recurrent bacterial infections of the respiratory and gastrointestinal tract. A significant proportion of CVID patients develops additional autoimmune, inflammatory or lymphoproliferative complications. CVID is the most frequent symptomatic primary immunodeficiency encountered in adults. Informative monogenetic defects have been found in single patients and families but in most cases the pathogenesis is still elusive. Numerous immunological studies have demonstrated phenotypic and functional abnormalities of T cells, B cells and antigen-presenting cells. A hallmark is the impaired memory B-cell formation that has been taken advantage of for classifying CVID patients. Clinical multi-center studies have demonstrated a correlation between immunological markers and clinical presentation. Long-term outcome is significantly influenced by delay of diagnosis and treatment and the presence of chronic inflammatory complications. While immunoglobulin replacement therapy plus antibiotics can control infections in most cases, patients with non-infectious inflammatory complications such as granulomatous inflammation, interstitial lung disease, inflammatory bowel disease, lymphoproliferation and developing malignancies still represent a therapeutic challenge. In this review we provide a systematic overview of the immunological, clinical, diagnostic and therapeutic aspects of CVID and highlight recent developments in these fields. PMID:23043756

2012-01-01

101

Establishment of monoclonal anti-human CD26 antibodies suitable for immunostaining of formalin-fixed tissue  

PubMed Central

Background A T cell costimulatory molecule with dipeptidyl peptidase IV (DPPIV) activity in its extracellular region, CD26 is a multifunctional molecule associated with various proteins such as adenosine deaminase, caveolin-1, CXCR4, collagen, and fibronectin, while playing an important role in the regulation of inflammatory responses and tumor biology. We have focused on CD26 as a novel therapeutic target for various tumors and immune disorders, and have developed a humanized anti-CD26 monoclonal antibody (mAb), YS110, which is currently being evaluated in a phase I clinical trial for patients with CD26-expressing tumors, including malignant mesothelioma. Since detection of tumor CD26 expression is required for determining potential eligibility for YS110 therapy, the development of anti-human CD26 mAb that can clearly and reliably detect the denatured CD26 molecule in the formalin-fixed paraffin-embedded tissues is critical. Methods To develop novel anti-CD26 mAbs capable of binding to the denatured CD26, we immunized mice with CD26 protein denatured in urea buffer. After the fusion of splenocytes and myeloma cells, the mAbs were screened for specific reactivity with human CD26 by flow cytometry, enzyme-linked immunosorbent assay, and immunohistochemistry. The binding competitiveness of novel anti-CD26 mAbs with the humanized anti-CD26 mAb YS110 was also examined. Results We have succeeded in developing novel anti-human CD26 mAbs suitable for immunohistochemical staining of CD26 in formalin-fixed tissue sections with reliable clarity and intensity. Importantly, some of these mAbs exhibit no cross-reactivity with the humanized anti-CD26 mAb. Conclusions These novel mAbs are potentially useful as companion diagnostic agents to analyze CD26 expression in the clinical setting while advancing future CD26-related research. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5987140221097729 PMID:24502396

2014-01-01

102

Two novel inhibitory anti-human factor XI antibodies prevent cessation of blood flow in a murine venous thrombosis model.  

PubMed

Coagulation factor XI (FXI) is a promising target for anticoagulation, because of its major role in thrombosis and relatively minor role in haemostasis. This implies that inhibition of FXI can prevent thrombosis without causing bleeding. It was our aim to investigate the antithrombotic properties of two novel inhibitory anti-human FXI antibodies (?FXI-175 and ?FXI-203). The in vitro properties of both antibodies were analysed using standard clotting assays and calibrated automated thrombography. For the in vivo model we used FXI knockout mice, in which FXI plasma levels were restored with purified human FXI. Thrombosis was induced by applying ferric chloride to the vena cava inferior, after which time to occlusion was analysed. A tail bleeding assay was used to investigate the safety of both antibodies. Using calibrated automated thrombography, both antibodies inhibited thrombin generation initiated via the intrinsic pathway. In contrast, upon tissue factor (TF)-initiated thrombin generation, ?FXI-203 did not inhibit thrombin generation, while ?FXI-175 inhibited thrombin generation only at low concentrations of TF. In the murine thrombosis model, the vena cava inferior remained patent for 25 minutes (min) in mice treated with ?FXI-175 and for 12.5 min in ?FXI-203 treated animals, which was significantly longer than in placebo-treated animals (5 min, p<0.05). Neither antibody caused severe blood loss in a tail bleeding assay. In conclusion, the two inhibitory antibodies against FXI prevented cessation of blood flow in a murine thrombosis model without inducing a bleeding tendency. PMID:23925504

van Montfoort, M L; Knaup, V L; Marquart, J A; Bakhtiari, K; Castellino, F J; Hack, C E; Meijers, J C M

2013-11-01

103

Current Perspectives on Primary Immunodeficiency Diseases  

PubMed Central

Since the original description of X-linked agammaglobulinemia in 1952, the number of independent primary immunodeficiency diseases (PIDs) has expanded to more than 100 entities. By definition, a PID is a genetically determined disorder resulting in enhanced susceptibility to infectious disease. Despite the heritable nature of these diseases, some PIDs are clinically manifested only after prerequisite environmental exposures but they often have associated malignant, allergic, or autoimmune manifestations. PIDs must be distinguished from secondary or acquired immunodeficiencies, which are far more common. In this review, we will place these immunodeficiencies in the context of both clinical and laboratory presentations as well as highlight the known genetic basis. PMID:17162365

Kumar, Arvind; Teuber, Suzanne S.; Gershwin, M. Eric

2006-01-01

104

Botryomycosis in acquired immunodeficiency syndrome.  

PubMed

The first case, to our knowledge, of an integumentary form of botryomycosis is reported in a homosexual man with acquired immunodeficiency syndrome. Anal fistula and ischiorectal and gluteal abscesses developed following severe cryptosporidial diarrhea. Grains composed of gram-positive cocci were identified in the suppurative exudate. The grains had attached to multinucleated macrophages, many of which contained clusters of cocci in their cytoplasm. It is postulated that the cocci were able to survive and probably replicate in the cytoplasm of multinucleated macrophages, and were subsequently extruded as grains. These observations suggest a defect in intracellular killing of cocci by the monocyte-macrophage system. This may relate to failure in induction of control of macrophage activity by T4-inducer subsets. PMID:3827528

Toth, I R; Kazal, H L

1987-03-01

105

Autoimmunity in Common Variable Immunodeficiency  

PubMed Central

Common variable immunodeficiency (CVID) is the most common clinically significant primary immune defect. Although the hallmark of CVID is hypogammaglobulinemia, the intrinsic dysregulation of the immune system leads to defective T-cell activation and proliferation, as well as dendritic cell and cytokine defects. Although 70% to 80% of patients have had recurrent sinopulmonary infections, auto-immunity and inflammatory complications are also common. The most common autoimmune conditions are immune thrombocytopenic purpura and hemolytic anemia, but other autoimmune complications arise, including rheumatoid arthritis, pernicious anemia, primary biliary cirrhosis, thyroiditis, sicca syndrome, systemic lupus, and inflammatory bowel disease. Treatment of autoimmunity includes high-dose immunoglobulins, corticosteroids, selected immunosuppressants, and other immune modulators. This review focuses on autoimmune conditions associated with CVID, potential mechanisms of immune dysregulation, and therapeutic strategies. PMID:19671377

Agarwal, Shradha; Cunningham-Rundles, Charlotte

2010-01-01

106

Use of Human Immunodeficiency Virus Nucleoside-Analog Reverse Transcriptase Inhibitors to Control Human Immunodeficiency Virus  

NSDL National Science Digital Library

This animation illustrates how human immunodeficiency virus (HIV) nucleoside-analog reverse transcriptase inhibitors (zidovudine, didanosine, zalcitabine, stavudine, lamivudine, and abacavir) inhibit replication of the HIV.

American Society For Microbiology;

2005-03-11

107

Laboratory diagnosis of primary immunodeficiencies.  

PubMed

Primary immune deficiency disorders represent a highly heterogeneous group of disorders with an increased propensity to infections and other immune complications. A careful history to delineate the pattern of infectious organisms and other complications is important to guide the workup of these patients, but a focused laboratory evaluation is essential to the diagnosis of an underlying primary immunodeficiency. Initial workup of suspected immune deficiencies should include complete blood counts and serologic tests of immunoglobulin levels, vaccine titers, and complement levels, but these tests are often insufficient to make a diagnosis. Recent advancements in the understanding of the immune system have led to the development of novel immunologic assays to aid in the diagnosis of these disorders. Classically utilized to enumerate lymphocyte subsets, flow cytometric-based assays are increasingly utilized to test immune cell function (e.g., neutrophil oxidative burst, NK cytotoxicity), intracellular cytokine production (e.g., TH17 production), cellular signaling pathways (e.g., phosphor-STAT analysis), and protein expression (e.g., BTK, Foxp3). Genetic testing has similarly expanded greatly as more primary immune deficiencies are defined, and the use of mass sequencing technologies is leading to the identification of novel disorders. In order to utilize these complex assays in clinical care, one must have a firm understanding of the immunologic assay, how the results are interpreted, pitfalls in the assays, and how the test affects treatment decisions. This article will provide a systematic approach of the evaluation of a suspected primary immunodeficiency, as well as provide a comprehensive list of testing options and their results in the context of various disease processes. PMID:24569953

Locke, Bradley A; Dasu, Trivikram; Verbsky, James W

2014-04-01

108

International Network for Comparison of HIV Neutralization Assays: The NeutNet Report  

Microsoft Academic Search

Background: Neutralizing antibody assessments play a central role in human immunodeficiency virus type-1 (HIV-1) vaccine development but it is unclear which assay, or combination of assays, will provide reliable measures of correlates of protection. To address this, an international collaboration (NeutNet) involving 18 independent participants was organized to compare different assays. Methods: Each laboratory evaluated four neutralizing reagents (TriMab, 447-52D,

Eva Maria Fenyö; Alan Heath; Stefania Dispinseri; Harvey Holmes; Paolo Lusso; Susan Zolla-Pazner; Helen Donners; Leo Heyndrickx; Jose Alcami; Vera Bongertz; Christian Jassoy; Mauro Malnati; David Montefiori; Christiane Moog; Lynn Morris; Saladin Osmanov; Victoria Polonis; Quentin Sattentau; Hanneke Schuitemaker; Ruengpung Sutthent; Terri Wrin; Gabriella Scarlatti

2009-01-01

109

Warts and All: HPV in Primary Immunodeficiencies  

PubMed Central

Infection with human papilloma virus (HPV) is almost universal and eventually asymptomatic, but pathologic infection with HPV is severe, recurrent, and recalcitrant to therapy. It is also an underappreciated manifestation of primary immunodeficiency. Mutations in EVER1, EVER2, GATA2, CXCR4, and DOCK8 are typically associated with extensive HPV infections, whereas several other primary immune defects have severe HPV much less frequently. We review immunodeficiencies with severe HPV infections and the mechanisms underlying them. PMID:23036745

Leiding, Jennifer W.; Holland, Steven M.

2012-01-01

110

History of Primary Immunodeficiency Diseases in Iran  

PubMed Central

Pediatric immunology came into sight in the second half of 20th century, when pediatricians and basic immunologists began to give attention to diagnosis and treatment of children with primary immunodeficiency diseases (PIDs). Understanding the genetic and mechanistic basis of PIDs provides unique insight into the functioning of the immune system. By progress in basic and clinical immunology, many infrastructural organizations and academic centers have been established in many countries worldwide to focus on training and research on the immune system and related disorders. Along with progress in basic and clinical immunology in the world, pediatric immunology had a good progress in Iran during the last 33-year period. Now, patients with PIDs can benefit from multidisciplinary comprehensive care, which is provided by clinical immunologists in collaboration with other specialists. Patients with history of recurrent and/or chronic infections suggestive of PIDs are evaluated by standard and research-based testing and receive appropriate treatment. The progress in PIDs can be described in three periods. Development of training program for clinical fellowship in allergy and immunology, multidisciplinary and international collaborative projects, primary immunodeficiency diseases textbooks, meetings on immunodeficiency disorders, improvement in diagnosis and treatment, and construction of Iranian primary immunodeficiency association, Students' research group for immunodeficiencies, Iranian primary immunodeficiency registry, and the immunological societies and centers were the main activities on PIDs during these years. In this article, we review the growth of modern pediatric immunology and PIDs status in Iran. PMID:23056678

Aghamohammadi, Asghar; Moin, Mostafa; Rezaei, Nima

2010-01-01

111

Improved Breadth and Potency of an HIV1Neutralizing Human Single-chain Antibody by Random Mutagenesis and Sequential Antigen Panning  

Microsoft Academic Search

Several human monoclonal antibodies can neutralize a range of human immunodeficiency virus type 1 (HIV-1) primary isolates but their potency and related ability to suppress generation of HIV-1 escape mutants is significantly lower than the activity of antiretroviral drugs currently in clinical use. Recently, a human Fab, X5, was identified and found to neutralize primary isolates from different clades. Further

Mei-Yun Zhang; Yuuei Shu; Donna Rudolph; Ponraj Prabakaran; Aran F. Labrijn; Michael B. Zwick; Renu B. Lal; Dimiter S. Dimitrov

2004-01-01

112

Alopecia Areata and Vitiligo as Primary Presentations in a Young Male with Human Immunodeficiency Virus  

PubMed Central

A 26-year-old Chinese male consulted with the team regarding his alopecia areata and vitiligo for which previous treatment was ineffective. The patient, a homosexual man, denied having a history of drug abuse and of blood transfusion. No member of his family had vitiligo or alopecia. Laboratory studies revealed that the serum for anti-human immunodeficiency virus (HIV) antibody was positive. The patient's CD4 lymphocyte count and CD4/CD8 ratio were both strikingly low (20 cells/mL and 0.04), but no other complaints or opportunistic infections were reported. One month after antiretroviral therapy, the patient's alopecia areata dramatically improved, but no evident improvement in his vitiligo was found. This case is a very rare case of alopecia areata and vitiligo associated with HIV infection that might be attributed to the generation and maintenance of self-reactive CD8+ T-cells due to chronic immune activation with progressive immune exhaustion in HIV infection. PMID:24700956

Xuan, Li; Baohua, Yang; Lan, Baohua

2014-01-01

113

Separation and partial characterization of proteinases with substrate specificity for basic amino acids from human MOLT-4 T lymphocytes: identification of those inhibited by variable-loop-V3 peptides of HIV-1 (human immunodeficiency virus-1) envelope glycoprotein.  

PubMed Central

The V3 loop of the HIV (human immunodeficiency virus)-1 envelope glycoprotein gp120 likely plays a role in HIV-1 infectivity. Although the amino acid sequence of the V3 loop is hypervariable, it contains a conserved region, Gly-Pro-Gly-Arg, that shows similarity to the active-site Gly-Pro-Cys-Arg sequence of inter-alpha-trypsin and trypstatin proteinase inhibitors. The purpose of the present work was to identify proteinases recognizing substrates with basic amino acids in the P1 substrate site that are present in MOLT-4 cells, a human CD4-positive T helper lymphocyte cell line, and to characterize these enzymes in terms of substrate, pH and ionic-strength preferences, size and susceptibility to various inhibitors, including 24- and 36-amino-acid-long V3 loop peptides. Extraction of MOLT-4 cells at low ionic strength solubilized nearly all of the trypsin-like activity, which was separable into five peaks of activity by chromatography on Mono-Q: Peaks 1, 2a, 2b, 3 and 4. All showed a neutral pH optimum, and all except Peak 4 showed optimal activity at high ionic strength. Peak 1 preferred Tos-Gly-Pro-Arg, p-nitroanilide (-pNA) substrate; Peaks 2-4 preferred benzyloxycarbonyl-Val-Leu-Gly-Arg-pNA. Peak 1, a zinc-dependent enzyme with serine and histidine in the active site, exhibited an M(r) of 75,000 on Superose 12 and was poorly inhibited by V3 loop peptides. Peak 2 contained two overlapping peaks, called 2a and 2b, that exhibited properties of zinc-dependent metalloproteinases. Gel filtration of Peak 2 activities revealed a major peak of activity at 81 kDa and a shoulder centred at 240 kDa. Each was modestly inhibited by V3 loop peptides. Peak 3, a zinc-dependent proteinase, exhibited a molecular mass of 100 kDa by gel filtration and was particularly sensitive to inhibition by V3 loop peptides. Peak 4 exhibited a molecular mass of 1100 kDa by gel filtration and was not inhibited by V3 loop peptides. None of these enzymes could be classified as mast-cell tryptase, and material in MOLT-4 cells cross-reactive with anti-(human tryptase) antibodies was not detected. Whether any of the MOLT-4 proteinases described in this study play a role in HIV-1 infectivity remains to be examined. PMID:8318003

Harvima, I T; Harvima, R J; Nilsson, G; Ivanoff, L; Schwartz, L B

1993-01-01

114

Human immunodeficiency virus & cardiovascular risk.  

PubMed

Highly active antiretroviral therapy (HAART) significantly changed the prevalence of the cardiovascular manifestations of human immunodeficiency virus (HIV)/AIDS. In developed countries, a 30 per cent reduction in the prevalence of cardiomyopathy and pericardial effusion was observed, possibly related to a reduction of opportunistic infections and myocarditis. In developing countries, however, where the availability of HAART is limited, and the pathogenic impact of nutritional factors is significant, a 32 per cent increase was seen in the prevalence of cardiomyopathy and related high mortality rate from congestive heart failure. Also, some HAART regimens in developed countries, especially those including protease inhibitors, may cause, in a high proportion of HIV-infected patients, a lipodystrophy syndrome that is associated with an increased risk of cardiovascular events related to a process of accelerated atherosclerosis. Careful cardiac screening is warranted for patients who are being evaluated for, or who are receiving HAART regimens, particularly for those with known underlying cardiovascular risk factors, according to the most recent clinical guidelines. PMID:22310821

Barbaro, Giuseppe; Barbarini, Giorgio

2011-12-01

115

Human immunodeficiency virus & cardiovascular risk  

PubMed Central

Highly active antiretroviral therapy (HAART) significantly changed the prevalence of the cardiovascular manifestations of human immunodeficiency virus (HIV)/AIDS. In developed countries, a 30 per cent reduction in the prevalence of cardiomyopathy and pericardial effusion was observed, possibly related to a reduction of opportunistic infections and myocarditis. In developing countries, however, where the availablity of HAART is limited, and the pathogenic impact of nutritional factors is significant, a 32 per cent increase was seen in the prevalence of cardiomyopathy and related high mortality rate from congestive heart failure. Also, some HAART regimens in developed countries, especially those including protease inhibitors, may cause, in a high proportion of HIV-infected patients, a lipodystrophy syndrome that is associated with an increased risk of cardiovascular events related to a process of accelerated atherosclerosis. Careful cardiac screening is warranted for patients who are being evaluated for, or who are receiving HAART regimens, particularly for those with known underlying cardiovascular risk factors, according to the most recent clinical guidelines. PMID:22310821

Barbaro, Giuseppe; Barbarini, Giorgio

2011-01-01

116

Brucella abortus conjugated with a gp120 or V3 loop peptide derived from human immunodeficiency virus (HIV) type 1 induces neutralizing anti-HIV antibodies, and the V3-B. abortus conjugate is effective even after CD4+ T-cell depletion.  

PubMed Central

Human immunodeficiency virus type 1 (HIV-1) infection is associated with loss of function and numbers of CD4+ T-helper cells. In order to bypass the requirement for CD4+ cells in antibody responses, we have utilized heat-inactivated Brucella abortus as a carrier. In this study we coupled a 14-mer V3 loop peptide (V3), which is homologous to 9 of 11 amino acids from the V3 loop of HIV-1 MN, and gp120 from HIV-1 SF2 to B. abortus [gp120(SF2)-B. abortus]. Our results showed that specific antibody responses, dominated by immunoglobulin G2a in BALB/c mice, were induced by these conjugates. Sera from the immunized mice bound native gp120 expressed on the surfaces of cells infected with a recombinant vaccinia virus gp160 vector (VPE16). Sera from mice immunized with gp120(SF2)-B. abortus inhibited binding of soluble CD4 to gp120, whereas sera from mice immunized with V3-B. abortus were ineffective. Sera from mice immunized with either conjugate were capable of blocking syncytium formation between CD4+ CEM cells and H9 cells chronically infected with the homologous virus. Sera from mice immunized with gp120(SF2)-B. abortus were more potent than sera from mice immunized with V3-B. abortus in inhibiting syncytia from heterologous HIV-1 laboratory strains. Importantly, in primary and secondary responses, V3-B. abortus evoked anti-HIV MN antibodies in mice depleted of CD4+ cells, and sera from these mice were able to inhibit syncytia. These findings indicate that B. abortus can provide carrier function for peptides and proteins from HIV-1 and suggest that they could be used for immunization of individuals with compromised CD4+ T-cell function. PMID:7745677

Golding, B; Inman, J; Highet, P; Blackburn, R; Manischewitz, J; Blyveis, N; Angus, R D; Golding, H

1995-01-01

117

Genetics Home Reference: ZAP70-related severe combined immunodeficiency  

MedlinePLUS

... with SCID lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated ... ZAP70-related severe combined immunodeficiency? autosomal ; autosomal recessive ; bacteria ; cell ; chronic ; deficiency ; gene ; immune system ; immunodeficiency ; infection ; ...

118

Genetics Home Reference: X-linked severe combined immunodeficiency  

MedlinePLUS

... PubMed Recent literature OMIM Genetic disorder catalog Conditions > X-linked severe combined immunodeficiency (often shortened to X- ... names Glossary definitions Reviewed May 2009 What is X-linked SCID? X-linked severe combined immunodeficiency (SCID) ...

119

Frequent Transmission of Immunodeficiency Viruses among Bobcats and Pumas  

Microsoft Academic Search

With the exception of human immunodeficiency virus (HIV), which emerged in humans after cross-species transmissions of simian immunodeficiency viruses from nonhuman primates, immunodeficiency viruses of the family Lentiviridae represent species-specific viruses that rarely cross species barriers to infect new hosts. Among the Felidae, numerous immunodeficiency-like lentiviruses have been documented, but only a few cross-species transmissions have been recorded, and these

S. P. Franklin; J. L. Troyer; J. A. Terwee; L. M. Lyren; W. M. Boyce; S. P. D. Riley; M. E. Roelke; K. R. Crooks; S. VandeWoude

2007-01-01

120

Vaginal infections in human immunodeficiency virus–infected women  

Microsoft Academic Search

Objective: This study was undertaken to compare the frequencies of vaginal infections among human immunodeficiency virus–infected women with those among human immunodeficiency virus–seronegative women. Study Design: Human immunodeficiency virus–seropositive women attending a comprehensive care center for human immunodeficiency virus disease at the outpatient department of an inner-city hospital in Houston underwent rigorous gynecologic evaluation for sexually transmitted diseases, including evidence

Andrew Helfgott; Nancy Eriksen; C. Michael Bundrick; Ronald Lorimor; Barbara Van Eckhout

2000-01-01

121

Common variable immunodeficiency complicated with hemolytic uremic syndrome  

PubMed Central

Common variable immunodeficiency is a primary immunodeficiency disease characterized by reduced serum immunoglobulins and heterogeneous clinical features. Recurrent pyogenic infections of upper and lower respiratory tracts are the main clinical manifestations of common variable immunodeficiency. Hemolytic uremic syndrome is a multisystemic disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ ischemia due to platelet aggregation in the arterial microvasculature. This is one of the rare cases of patients diagnosed with common variable immunodeficiency, which was complicated by hemolytic uremic syndrome. PMID:22059898

2012-01-01

122

Mutation and Control of the Human Immunodeficiency Virus  

E-print Network

Mutation and Control of the Human Immunodeficiency Virus Robert F. Stengel Princeton University of infection by the hu- man immunodeficiency virus (HIV), as well as therapies that minimize viral load the relative fitness of mutant strains. Index Terms ­ Human immunodeficiency virus, immune system dynamics

Stengel, Robert F.

123

Neutral beam monitoring  

DOEpatents

Method and apparatus for monitoring characteristics of a high energy neutral beam. A neutral beam is generated by passing accelerated ions through a walled cell containing a low energy neutral gas, such that charge exchange neutralizes the high energy ion beam. The neutral beam is monitored by detecting the current flowing through the cell wall produced by low energy ions which drift to the wall after the charge exchange. By segmenting the wall into radial and longitudinal segments various beam conditions are further identified.

Fink, Joel H. (Livermore, CA)

1981-08-18

124

Oral Manifestations of Human Immunodeficiency Virus Infection  

PubMed Central

The AIDS epidemic continues. All health-care workers, including physicians and dental personnel, may be instrumental in recognizing risk factors associated with Acquired Immunodeficiency Syndrome (AIDS) and Human Immunodeficiency Virus (HIV) infection. Oral signs and symptoms of HIV infection may be the first presentation of the disease or may develop during the course of the disease and require management. Knowledge of the signs, symptoms and associated infections and tumours is needed to assist in recognition, diagnosis, and treatment. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8Figure 9Figure 10Figure 11Figure 12Figure 13 PMID:21253078

Epstein, Joel B.; Mathias, Richard G.

1988-01-01

125

Protective effects of HFE7A, mouse anti-human\\/mouse Fas monoclonal antibody against acute and lethal hepatic injury induced by Jo2  

Microsoft Academic Search

HFE7A is a mouse anti-human\\/mouse Fas monoclonal antibody which, protects mice from fulminant hepatitis induced by Jo2. Herein,\\u000a we report on the mechanism of the protective effect of HFE7A against Jo2-induced acute and lethal hepatic injury. HFE7A reduced\\u000a the serum aminotransferase level which was elevated after Jo2 injection. HFE7A also inhibited caspase activation and mitochondrial\\u000a depolarization in hepatocytes derived from

Hiroko Yoshida; Kenji Watanabe; Shu Takahashi; Kimihisa Ichikawa

2010-01-01

126

Women at Risk for Human Immunodeficiency Virus.  

ERIC Educational Resources Information Center

This article reports results from a survey among women at risk for contracting Human Immunodeficiency Virus (HIV) as well as transmitting it in a vertical (to offspring) and horizontal (sexual partner or intravenous [IV] drug usage) mode. Little is known about the extent of HIV knowledge, sexual behaviors, and IV drug usage for women at risk for…

Quadagno, David; And Others

127

Cardiac sequelae of human immunodeficiency virus disease.  

PubMed

Presently, patients with human immunodeficiency virus infection are living longer and are frequently encountered in medical practice. HIV infection is a systemic disease, which affects a wide spectrum of organs. Cardiac involvement is frequent, and the consequent clinical manifestations are a common reason to seek medical advice. In this review, we discuss the different cardiac sequelae of HIV infection. PMID:24743404

Alqaqa, Ashraf; Suleiman, Addi; Birnhak, Stefani; Tariq, Saad; Sison, Raymund; Hamdan, Aiman; DeBari, Vincent A; Shamoon, Fayez

2014-07-01

128

Immunodeficiency and laser magnetic therapy in urology  

Microsoft Academic Search

The importance of immunodeficiency problem has increased last time not only due to AIDS appearance, but also to a great extent as a result of the development and active practical use of the methods of immunology parameters investigations. Al great pharmaceutical firms are organizing the process of creating the drugs, influencing on the different phases of immunity, but unfortunately, the

Moufagued Maati; Vladimir V. Rozanov; V. P. Avdoshin

1996-01-01

129

Development of a complete human anti-human transferrin receptor C antibody as a novel marker of oral dysplasia and oral cancer  

PubMed Central

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide. Up to 20% of oral dysplasia cases have been suggested to undergo malignant transformation to OSCC; however, there are no methods to predict OSCC development. In this study, to identify the genes associated with oral dysplasia progression, we performed genomic copy number analyses of genomic DNA samples isolated from primary oral dysplasia and OSCC via the microdissection method and found elevated expression of transferrin receptor C (TfR1/TFRC) with genomic amplification in oral dysplasia and OSCC. The expression rate of TFRC in OSCC was significantly higher than that in dysplasia, suggesting that OSCC disease progression might be related to TFRC expression. Additionally, we investigated the in vitro and in vivo impacts of a newly established anti-human TFRC monoclonal antibody, which was isolated from a human cDNA library using the phage-display method, on cell proliferation and survival. The anti-TFRC antibody blocked the interaction between transferrin and TFRC and consequently inhibited iron uptake, leading to the iron deprivation-mediated suppression of cell growth and induction of apoptosis. Moreover, we demonstrated that the anti-TFRC antibody efficiently inhibited tumor growth in a murine xenograft OSCC model. Therefore, we suggest our developed complete human anti-human TFRC antibody as a useful, novel treatment for oral dysplasia and OSCC. PMID:24890018

Nagai, Kentaro; Nakahata, Shingo; Shimosaki, Shunsuke; Tamura, Tomohiro; Kondo, Yuudai; Baba, Takashi; Taki, Tomohiko; Taniwaki, Masafumi; Kurosawa, Gene; Sudo, Yukio; Okada, Seiji; Sakoda, Sumio; Morishita, Kazuhiro

2014-01-01

130

Neutralizing Acids and Bases  

NSDL National Science Digital Library

Learners use their knowledge of color changes with red cabbage indicator to neutralize an acidic solution with a base and then neutralize a basic solution with an acid. Use this as a follow-up activity to the related activity, "Color Changes with Acids and Bases."

2012-04-08

131

Mutation at a single position in the V2 domain of the HIV-1 envelope protein confers neutralization sensitivity to a highly neutralization-resistant virus.  

PubMed

Understanding the determinants of neutralization sensitivity and resistance is important for the development of an effective human immunodeficiency virus type 1 (HIV-1) vaccine. In these studies, we have made use of the swarm of closely related envelope protein variants (quasispecies) from an extremely neutralization-resistant clinical isolate in order to identify mutations that conferred neutralization sensitivity to antibodies in sera from HIV-1-infected individuals. Here, we describe a virus with a rare mutation at position 179 in the V2 domain of gp120, where replacement of aspartic acid (D) by asparagine (N) converts a virus that is highly resistant to neutralization by multiple polyclonal and monoclonal antibodies, as well as antiviral entry inhibitors, to one that is sensitive to neutralization. Although the V2 domain sequence is highly variable, D at position 179 is highly conserved in HIV-1 and simian immunodeficiency virus (SIV) and is located within the LDI/V recognition motif of the recently described ?4?7 receptor binding site. Our results suggest that the D179N mutation induces a conformational change that exposes epitopes in both the gp120 and the gp41 portions of the envelope protein, such as the CD4 binding site and the MPER, that are normally concealed by conformational masking. Our results suggest that D179 plays a central role in maintaining the conformation and infectivity of HIV-1 as well as mediating binding to ?4?7. PMID:20702624

O'Rourke, Sara M; Schweighardt, Becky; Phung, Pham; Fonseca, Dora P A J; Terry, Karianne; Wrin, Terri; Sinangil, Faruk; Berman, Phillip W

2010-11-01

132

Agreement study between two laboratories of immunofluorescence as a confirmatory test for human immunodeficiency virus type 1 antibody screening.  

PubMed Central

A total of 114 serum specimens from 76 blood donors, 21 patients with acquired immune deficiency syndrome or acquired immune deficiency syndrome-related complex, 7 multiply transfused patients, 3 hemophiliacs, and 7 others were tested for anti-human immunodeficiency virus type 1 (HIV-1) antibody by enzyme immunoassay (EIA) and Western blot (WB) and then blindly tested by immunofluorescence (IF), independently, in two separate laboratories. The IF technique used acetone-fixed HIV-1-infected E cells and uninfected HUT-78 cells mixed at a 1:3 ratio in one spot on a glass slide and uninfected HUT-78 cells (to assess nonspecific fluorescence) alone in a second spot. Of 114 serum specimens, 85 were repeat EIA positive, and 21 of these were WB positive. A total of 129 of 134 of the IF results (included were 20 duplicates) were identical between laboratories, for a Kappa agreement statistic of 0.93. All five IF results discordant between laboratories were EIA repeat positive and WB negative. Included in the study were eight WB-indeterminate sera, of which five blood donor serum specimens and one hemophiliac serum specimen were IF negative and two acquired immune deficiency syndrome serum specimens were IF positive. As a confirmatory test for HIV-1 antibodies, IF provided a faster alternative or supplementary test for confirming EIA results. PMID:2666438

Mahony, J; Rosenthal, K; Chernesky, M; Castriciano, S; Scheid, E; Blajchman, M; Harnish, D

1989-01-01

133

Organising pneumonia in common variable immunodeficiency.  

PubMed

Common variable immunodeficiency (CVID) is the most common of the primary immunodeficiency disorders. Pulmonary manifestations are characterised by recurrent rhinosinusitis, respiratory tract infections and bronchiectasis. Less commonly the lung may be affected by lymphoid disorders and sarcoid-like granulomas. Organising pneumonia (OP) is a rare pulmonary manifestation. We report the case of a 32-year-old woman with CVID who presented with fever, dyspnoea and persistent lung infiltrates despite antibiotic therapy. CT of the chest showed bilateral patchy alveolar infiltrates. Pulmonary function tests revealed moderate restriction and reduction in diffusion capacity. Initial bronchoscopy with transbronchial biopsies did not yield a diagnosis but surgical lung biopsies identified OP. Significant clinical, radiographic and physiological improvement was achieved after institution of corticosteroid therapy. PMID:23749855

Boujaoude, Ziad; Arya, Rohan; Rafferty, William; Dammert, Pedro

2013-01-01

134

Genetic Defects of Apoptosis and Primary Immunodeficiency  

PubMed Central

Synopsis Programmed cell death is important for maintaining lymphocyte homeostasis. Several human inherited diseases with impaired apoptosis have been identified at the genetic level: autoimmune lymphoproliferative syndrome (ALPS), caspase-8 deficiency state (CEDS), and X-linked lymphoproliferative syndrome (XLP). These diseases feature excess lymphocyte accumulation, autoimmunity, and/or immunodeficiency. Elucidating their molecular pathogenesis has also provided new insights into the signaling mechanisms regulating apoptosis and lymphocyte activation. PMID:18424336

Su, Helen C.; Lenardo, Michael J.

2009-01-01

135

Feline Immunodeficiency Virus in South America  

PubMed Central

The rapid emergence of AIDS in humans during the period between 1980 and 2000 has led to extensive efforts to understand more fully similar etiologic agents of chronic and progressive acquired immunodeficiency disease in several mammalian species. Lentiviruses that have gene sequence homology with human immunodeficiency virus (HIV) have been found in different species (including sheep, goats, horses, cattle, cats, and several Old World monkey species). Lentiviruses, comprising a genus of the Retroviridae family, cause persistent infection that can lead to varying degrees of morbidity and mortality depending on the virus and the host species involved. Feline immunodeficiency virus (FIV) causes an immune system disease in domestic cats (Felis catus) involving depletion of the CD4+ population of T lymphocytes, increased susceptibility to opportunistic infections, and sometimes death. Viruses related to domestic cat FIV occur also in a variety of nondomestic felids. This is a brief overview of the current state of knowledge of this large and ancient group of viruses (FIVs) in South America. PMID:22590677

Teixeira, Bruno M.; Hagiwara, Mitika K.; Cruz, Juliano C. M.; Hosie, Margaret J.

2012-01-01

136

Attentiveness of pediatricians to primary immunodeficiency disorders  

PubMed Central

Background Primary immunodeficiency (PID) is a cluster of serious disorders that requires special alertness on the part of the medical staff for prompt diagnosis and management of the patient. This study explored PID knowledge and experience among pediatricians of wide educational backgrounds, practicing in the United Arab Emirates (UAE). Method A self-administered questionnaire was used to determine the competency of pediatricians in their knowledge of PID disorders. This study questionnaire included questions on PID signs and symptoms, syndromes associated with immunodeficiency, screening tests, interpreting laboratory tests and case management. The participants were 263 pediatricians of diverse education working in the 27 governmental hospitals in all regions of UAE. Results The overall performance of the pediatricians did not differ based on their age, gender, origin of certification, rank, or years of experience. Of the 50 questions, 20% of pediatricians answered correctly <60% of the questions, 76% answered correctly 60 to 79% of the questions, and 4% answered correctly ?80% of the questions. Seventeen of the 19 PID signs and symptoms were identified by 55 to 97%. Four of 5 syndromes associated with immunodeficiency were identified by 50 to 90%. Appropriate screening tests were chosen by 64 to 96%. Attention to the laboratory reference range values as function of patient age was notably limited. Conclusions There was a noteworthy deficiency in PID work-up. Therefore, implementing effective educational strategies is needed to improve the competency of pediatricians to diagnose and manage PID disorders. PMID:22846098

2012-01-01

137

Pharmacological Inhibition of Feline Immunodeficiency Virus (FIV)  

PubMed Central

Feline immunodeficiency virus (FIV) is a member of the retroviridae family of viruses and causes an acquired immunodeficiency syndrome (AIDS) in domestic and non-domestic cats worldwide. Genome organization of FIV and clinical characteristics of the disease caused by the virus are similar to those of human immunodeficiency virus (HIV). Both viruses infect T lymphocytes, monocytes and macrophages, and their replication cycle in infected cells is analogous. Due to marked similarity in genomic organization, virus structure, virus replication and disease pathogenesis of FIV and HIV, infection of cats with FIV is a useful tool to study and develop novel drugs and vaccines for HIV. Anti-retroviral drugs studied extensively in HIV infection have targeted different steps of the virus replication cycle: (1) inhibition of virus entry into susceptible cells at the level of attachment to host cell surface receptors and co-receptors; (2) inhibition of fusion of the virus membrane with the cell membrane; (3) blockade of reverse transcription of viral genomic RNA; (4) interruption of nuclear translocation and viral DNA integration into host genomes; (5) prevention of viral transcript processing and nuclear export; and (6) inhibition of virion assembly and maturation. Despite much success of anti-retroviral therapy slowing disease progression in people, similar therapy has not been thoroughly investigated in cats. In this article we review current pharmacological approaches and novel targets for anti-lentiviral therapy, and critically assess potentially suitable applications against FIV infection in cats. PMID:22754645

Mohammadi, Hakimeh; Bienzle, Dorothee

2012-01-01

138

Feline immunodeficiency virus in South America.  

PubMed

The rapid emergence of AIDS in humans during the period between 1980 and 2000 has led to extensive efforts to understand more fully similar etiologic agents of chronic and progressive acquired immunodeficiency disease in several mammalian species. Lentiviruses that have gene sequence homology with human immunodeficiency virus (HIV) have been found in different species (including sheep, goats, horses, cattle, cats, and several Old World monkey species). Lentiviruses, comprising a genus of the Retroviridae family, cause persistent infection that can lead to varying degrees of morbidity and mortality depending on the virus and the host species involved. Feline immunodeficiency virus (FIV) causes an immune system disease in domestic cats (Felis catus) involving depletion of the CD4+ population of T lymphocytes, increased susceptibility to opportunistic infections, and sometimes death. Viruses related to domestic cat FIV occur also in a variety of nondomestic felids. This is a brief overview of the current state of knowledge of this large and ancient group of viruses (FIVs) in South America. PMID:22590677

Teixeira, Bruno M; Hagiwara, Mitika K; Cruz, Juliano C M; Hosie, Margaret J

2012-03-01

139

Immunodeficiency after major trauma and selective surgery.  

PubMed

The posttrauma immunodeficiency syndrome and the related postsurgery immunodeficiency syndrome are essential for the infections often occurring after polytrauma and major surgery. Data are given here showing that after such events the levels of immunoglobulins; the complement factors C3C, C4 and C Factor B; and the numbers of circulating lymphocytes and of the subpopulations CD3, CD4, CD8 and natural killer cells as well as the stimulatory capacity of mononuclear cells to mitogen fall; while the levels of acute phase proteins, neopterin and interleukin 2 receptors and the spontaneous uptake of thymidine by mononuclear cells become augmented. Extent and duration of these changes and the rate of subsequent infections depend on the extent and kind of surgery (minor, major, clean, contaminated). However, crucial factors of the posttrauma and postsurgery immunodeficiency syndromes are not yet elucidated and relevant predictive parameters for infections are not at hand. These are essential prerequisites to initiate future immunomodulatory measures which should be added to the use of intravenous immunoglobulins yielding so far distinct but limited benefits for the prevention of infections after polytrauma and major surgery. PMID:3399284

Grob, P; Holch, M; Fierz, W; Glinz, W; Geroulanos, S

1988-05-01

140

Is dispersal neutral?  

PubMed

Dispersal is difficult to quantify and often treated as purely stochastic and extrinsically controlled. Consequently, there remains uncertainty about how individual traits mediate dispersal and its ecological effects. Addressing this uncertainty is crucial for distinguishing neutral versus non-neutral drivers of community assembly. Neutral theory assumes that dispersal is stochastic and equivalent among species. This assumption can be rejected on principle, but common research approaches tacitly support the 'neutral dispersal' assumption. Theory and empirical evidence that dispersal traits are under selection should be broadly integrated in community-level research, stimulating greater scrutiny of this assumption. A tighter empirical connection between the ecological and evolutionary forces that shape dispersal will enable richer understanding of this fundamental process and its role in community assembly. PMID:24962790

Lowe, Winsor H; McPeek, Mark A

2014-08-01

141

Modeling Thermospheric Neutral Density.  

E-print Network

??Satellite drag prediction requires determination of thermospheric neutral density. The NCAR Thermosphere-Ionosphere-Electrodynamics General Circulation Model (TIEGCM) and the global-mean Thermosphere-Ionosphere-Mesosphere-Electrodynamics General Circulation Model (TIMEGCM) were… (more)

Qian, Liying

2007-01-01

142

The neutral theory is dead. Long live the neutral theory  

E-print Network

on gene frequencies under the completely neutral theory, but it is also the driving force for mutationsDebate The neutral theory is dead. Long live the neutral theory Martin Kreitman Summary The neutral theory of molecular evolution has been instrumental in organizing our thinking about the nature

143

Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome: Correlation but not Causation  

Microsoft Academic Search

AIDS is an acquired immunodeficiency syndrome defined by a severe depletion of T cells and over 20 conventional degenerative and neoplastic diseas es. In the U.S. and Europe, AIDS correlates to 95% with risk factors, such as about 8 years of promiscuous male homosexuality, intravenous drug use, or hemophilia. Since AIDS also correlates with antibody to a retrovirus, confirmed in

Peter H. Duesberg

1989-01-01

144

Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome: Correlation but not Causation  

Microsoft Academic Search

AIDS is an acquired immunodeficiency syndrome defined by a severe depletion of T cells and over 20 conventional degenerative and neoplastic diseases. In the U.S. and Europe, AIDS correlates to 95% with risk factors, such as about 8 years of promiscuous male homosexuality, intravenous drug use, or hemophilia. Since AIDS also correlates with antibody to a retrovirus, confirmed in about

Peter H. Duesberg

1989-01-01

145

Impact of Simian Immunodeficiency Virus Infection on Chimpanzee Population Dynamics  

Microsoft Academic Search

Like human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus of chimpanzees (SIVcpz) can cause CD4+ T cell loss and premature death. Here, we used molecular surveillance tools and mathematical modeling to estimate the impact of SIVcpz infection on chimpanzee population dynamics. Habituated (Mitumba and Kasekela) and non-habituated (Kalande) chimpanzees were studied in Gombe National Park, Tanzania. Ape population sizes

Rebecca S. Rudicell; James Holland Jones; Emily E. Wroblewski; Gerald H. Learn; Yingying Li; Joel D. Robertson; Elizabeth Greengrass; Falk Grossmann; Shadrack Kamenya; Lilian Pintea; Deus C. Mjungu; Elizabeth V. Lonsdorf; Anna Mosser; Clarence Lehman; D. Anthony Collins; Brandon F. Keele; Jane Goodall; Beatrice H. Hahn; Anne E. Pusey; Michael L. Wilson

2010-01-01

146

Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies  

ClinicalTrials.gov

Immunologic Deficiency Syndromes; Chediak-Higashi Syndrome; Common Variable Immunodeficiency; Graft Versus Host Disease; X-Linked Lymphoproliferative Syndrome; Familial Erythrophagocytic Lymphohistiocytosis; Hemophagocytic Lymphohistiocytosis; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; X-linked Hyper IgM Syndrome; Severe Combined Immunodeficiency; Leukocyte Adhesion Deficiency Syndrome; Virus-Associated Hemophagocytic Syndrome

2009-10-14

147

Barrier methods for human immunodeficiency virus prevention.  

PubMed

Condoms remain the most effective barrier against the sexual transmission of the human immunodeficiency virus (HIV). Male condoms have proven to be 80% to 90% effective, and female condoms have similar results. Poor adherence and improper use limit their effectiveness. In addition to condoms, microbicides are a promising barrier against HIV transmission. More than 50 candidate topical microbicide compounds have undergone preclinical or clinical testing in the last 10 years, but there are currently no US Food and Drug Administration (FDA)-approved compounds. Rectal microbicides are also being developed, as anal receptive sex is an effective mode of HIV transmission. PMID:25455315

Eaton, Ellen F; Hoesley, Craig J

2014-12-01

148

Human Immunodeficiency Virus and Pulmonary Arterial Hypertension  

PubMed Central

Human immunodeficiency virus- (HIV-) related pulmonary arterial hypertension (PAH) is a rare complication of HIV infection. The pathophysiology of HIV-related PAH is complex, with viral proteins seeming to play the major role. However, other factors, such as coinfection with other microorganisms and HIV-related systemic inflammation, might also contribute. The clinical presentation of HIV-related PAH and diagnosis is similar to other forms of pulmonary hypertension. Both PAH-specific therapies and HAART are important in HIV-related PAH management. Future studies investigating the pathogenesis are needed to discover new therapeutic targets and treatments. PMID:24027641

Ali, Alaa M.

2013-01-01

149

Feline immunodeficiency virus: an interesting model for AIDS studies and an important cat pathogen.  

PubMed Central

The lentivirus feline immunodeficiency virus (FIV) is a widespread pathogen of the domestic cat that is mainly transmitted through bites, although other means of transmission are also possible. Its prevalence ranges from 1 to 10% in different cat populations throughout the world, thus representing a large reservoir of naturally infected animals. FIV resembles the human immunodeficiency virus (HIV) in many respects. Similarities include the structural features of the virion, the general organization and great variability of the genome, the life cycle in the infected host, and most importantly, the pathogenic potential. Infection is associated with laboratory signs of immunosuppression as well as with a large variety of superinfections, tumors, and neurological manifestations. Our understanding of FIV is steadily improving and is providing important clues to the pathogenesis of immunodeficiency-inducing lentiviruses. The cellular receptor for FIV is different from the feline equivalent of the human CD4 molecule used by HIV; nevertheless, the major hallmark of infection is a progressive loss of CD4+ T lymphocytes as in HIV infection. The mechanisms by which FIV escapes the host's immune responses are being actively investigated. FIV causes lysis of infected T cells and also appears to predispose these cells to apoptosis. Infection of macrophages and other cell types has also been documented. For reasons yet to be understood, antibody-mediated neutralization of fresh FIV isolates is very inefficient both in vitro and in vivo. Vaccination studies have provided some encouraging results, but the difficulties encountered appear to match those met in HIV vaccine development. FIV susceptibility to antiviral agents is similar to that of HIV, thus providing a valuable system for in vivo preclinical evaluation of therapies. It is concluded that in many respects FIV is an ideal model for AIDS studies. PMID:7704896

Bendinelli, M; Pistello, M; Lombardi, S; Poli, A; Garzelli, C; Matteucci, D; Ceccherini-Nelli, L; Malvaldi, G; Tozzini, F

1995-01-01

150

Bleach Neutralizes Mold Allergens  

ERIC Educational Resources Information Center

Researchers at National Jewish Medical and Research Center have demonstrated that dilute bleach not only kills common household mold, but may also neutralize the mold allergens that cause most mold-related health complaints. The study, published in the Journal of Allergy and Clinical Immunology, is the first to test the effect on allergic…

Science Teacher, 2005

2005-01-01

151

Magnetic nanocomposite of anti-human IgG/COOH-multiwalled carbon nanotubes/Fe?O? as a platform for electrochemical immunoassay.  

PubMed

An electrochemical immunosensing method was developed based on a magnetic nanocomposite. The multiwalled carbon nanotubes (MWCNTs) were treated with nitric acid to produce carboxyl groups at the open ends. Then, Fe?O? nanoparticles were deposited on COOH-MWCNTs by chemical coprecipitation of Fe²? and Fe³? salts in an alkaline solution. Goat anti-human IgG (anti-hIgG) was covalently attached to magnetic nanocomposite through amide bond formation between the carboxylic groups of MWCNTs and the amine groups of anti-hIgG. The prepared bio-nanocomposite was used for electrochemical sensing of human tetanus IgG (hIgG) as a model antigen. The anti-hIgG magnetic nanocomposite was fixed on the surface of a gold plate electrode using a permanent magnet. The hIgG was detected using horseradish peroxidase (HRP)-conjugated anti-hIgG in a sandwich model. Electrochemical detection of hIgG was carried out in the presence of H?O? and KI as substrates of HRP. Using this method, hIgG was detected in a concentration range from 30 to 1000 ng ml?¹ with a correlation coefficient of 0.998 and a detection limit of 25 ng ml?¹ (signal/noise=3). The designed immunosensor was stable for 1 month. PMID:22245258

Zarei, Hajar; Ghourchian, Hedayatollah; Eskandari, Khadijeh; Zeinali, Majid

2012-02-15

152

Protective effects of HFE7A, mouse anti-human/mouse Fas monoclonal antibody against acute and lethal hepatic injury induced by Jo2  

PubMed Central

HFE7A is a mouse anti-human/mouse Fas monoclonal antibody which, protects mice from fulminant hepatitis induced by Jo2. Herein, we report on the mechanism of the protective effect of HFE7A against Jo2-induced acute and lethal hepatic injury. HFE7A reduced the serum aminotransferase level which was elevated after Jo2 injection. HFE7A also inhibited caspase activation and mitochondrial depolarization in hepatocytes derived from apoptosis induced by Jo2 injection. The protective effect of HFE7A against Jo2-induced apoptosis in mouse hepatocytes was reproducible in vitro. The cell death and caspase activation in isolated mouse hepatocytes were induced by incubating these cells with Jo2 in vitro, and HFE7A inhibited the cell death and caspase activation in mouse hepatocytes in a dose-dependent manner. The affinity of HFE7A to mouse Fas was lower than that of Jo2. The binding of Jo2 to neither recombinant mouse Fas nor mouse hepatocytes was inhibited by an excessive amount of HFE7A. Interestingly, HFE7A bound to hepatocytes isolated from Fas knockout mice. From these results, it is suggested that HFE7A may exert a protective effect against Jo2-induced hepatitis not by competitively inhibiting the binding of Jo2 to Fas on hepatocytes, and that a distinct molecule other than Fas may possibly be involved in the protective effect of HFE7A against Jo2-induced hepatic injury. PMID:20024619

Watanabe, Kenji; Takahashi, Shu; Ichikawa, Kimihisa

2009-01-01

153

Unexplained fetal death has a biological signature of maternal anti-fetal rejection: chronic chorioamnionitis and alloimmune anti-human leucocyte antigen antibodies  

PubMed Central

Aims Chronic chorioamnionitis is a histological manifestation of maternal anti-fetal cellular rejection. Failure of graft survival being the most catastrophic event in organ transplantation, we hypothesized that fetal death could be a consequence of rejection of the mother against the fetus. This study was conducted to assess evidence of cellular and antibody-mediated rejection in fetal death cases. Methods and results Placental histology was reviewed for the presence of chronic chorioamnionitis in unexplained preterm fetal death (n=30) and preterm live birth (n=103) cases. Amniotic fluid CXCL10 concentrations were measured by specific immunoassay. Chronic chorioamnionitis was more frequent in fetal death cases than in live birth cases (60.0% versus 37.9%; P<0.05) and fetal death cases had a higher median amniotic fluid CXCL10 concentration than live birth cases (2.0 ng/ml versus 1.8 ng/ml, P<0.05), after adjusting for gestational age at amniocentesis. Maternal anti-human leucocye antigen (HLA) class II seropositivity determined by flow cytometry was higher in fetal death cases compared to live birth cases (35.7% versus 10.9%; P<0.05). Conclusions Chronic chorioamnionitis is a common pathology of unexplained preterm fetal death. The novel findings herein suggest strongly that cellular and antibody-mediated anti-fetal rejection of the mother is associated with fetal death (graft failure) in human pregnancy. PMID:22092404

Lee, JoonHo; Romero, Roberto; Dong, Zhong; Xu, Yi; Qureshi, Faisal; Jacques, Suzanne; Yoo, Wonsuk; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Hassan, Sonia S.; Kim, Chong Jai

2013-01-01

154

Lysis of human immunodeficiency virus type 1 by a specific secreted human phospholipase A2.  

PubMed

Phospholipase A2 (PLA2) proteins affect cellular activation, signal transduction, and possibly innate immunity. A specific secretory PLA2, sPLA2-X, is shown here to neutralize human immunodeficiency virus type 1 (HIV-1) through degradation of the viral membrane. Catalytic function was required for antiviral activity, and the target cells of infection were unaffected. sPLA2-X potently reduced gene transfer of HIV-1 Env-pseudotyped lentivirus vectors and inhibited the replication of both CCR5- and CXCR4-tropic HIV-1 in human CD4+ T cells. Virions resistant to damage by antibody and complement were sensitive to lysis by sPLA2-X, suggesting a novel mechanism of antiviral surveillance independent of the acquired immune system. PMID:17093191

Kim, Jae-Ouk; Chakrabarti, Bimal K; Guha-Niyogi, Anuradha; Louder, Mark K; Mascola, John R; Ganesh, Lakshmanan; Nabel, Gary J

2007-02-01

155

Infection of monkeys by simian-human immunodeficiency viruses with transmitted/founder clade C HIV-1 envelopes.  

PubMed

Simian-human immunodeficiency viruses (SHIVs) that mirror natural transmitted/founder (T/F) viruses in man are needed for evaluation of HIV-1 vaccine candidates in nonhuman primates. Currently available SHIVs contain HIV-1 env genes from chronically-infected individuals and do not reflect the characteristics of biologically relevant HIV-1 strains that mediate human transmission. We chose to develop clade C SHIVs, as clade C is the major infecting subtype of HIV-1 in the world. We constructed 10 clade C SHIVs expressing Env proteins from T/F viruses. Three of these ten clade C SHIVs (SHIV KB9 C3, SHIV KB9 C4 and SHIV KB9 C5) replicated in naïve rhesus monkeys. These three SHIVs are mucosally transmissible and are neutralized by sCD4 and several HIV-1 broadly neutralizing antibodies. However, like natural T/F viruses, they exhibit low Env reactivity and a Tier 2 neutralization sensitivity. Of note, none of the clade C T/F SHIVs elicited detectable autologous neutralizing antibodies in the infected monkeys, even though antibodies that neutralized a heterologous Tier 1 HIV-1 were generated. Challenge with these three new clade C SHIVs will provide biologically relevant tests for vaccine protection in rhesus macaques. PMID:25462344

Asmal, Mohammed; Luedemann, Corinne; Lavine, Christy L; Mach, Linh V; Balachandran, Harikrishnan; Brinkley, Christie; Denny, Thomas N; Lewis, Mark G; Anderson, Hanne; Pal, Ranajit; Sok, Devin; Le, Khoa; Pauthner, Matthias; Hahn, Beatrice H; Shaw, George M; Seaman, Michael S; Letvin, Norman L; Burton, Dennis R; Sodroski, Joseph G; Haynes, Barton F; Santra, Sampa

2015-01-15

156

Human immunodeficiency virus arteriopathy of the adult cerebral circulation.  

PubMed

Arteriopathy associated with human immunodeficiency virus infection and clinical acquired immunodeficiency syndrome is well-documented. The pathophysiology of this arteriopathy may vary in different vascular beds. Although arteriopathy of central nervous system (CNS) circulation has been recognized in pediatric patients since the late 1980s, there are no reported cases of CNS arteriopathy in adults. We present the first reported case of adult CNS arteriopathy in a human immunodeficiency virus-positive patient who succumbed to complications secondary to diffuse aneurysmal disease of the Circle of Willis. PMID:17615850

Statler, John D; Slaughter, C Ryan; Ronsivalle, Joseph A

2007-06-01

157

Generation of Infectious Molecular Clones of Simian Immunodeficiency Virus from Fecal Consensus Sequences of Wild Chimpanzees?  

PubMed Central

Studies of simian immunodeficiency viruses (SIVs) in their endangered primate hosts are of obvious medical and public health importance, but technically challenging. Although SIV-specific antibodies and nucleic acids have been detected in primate fecal samples, recovery of replication-competent virus from such samples has not been achieved. Here, we report the construction of infectious molecular clones of SIVcpz from fecal viral consensus sequences. Subgenomic fragments comprising a complete provirus were amplified from fecal RNA of three wild-living chimpanzees and sequenced directly. One set of amplicons was concatenated using overlap extension PCR. The resulting clone (TAN1.24) contained intact genes and regulatory regions but was replication defective. It also differed from the fecal consensus sequence by 76 nucleotides. Stepwise elimination of all missense mutations generated several constructs with restored replication potential. The clone that yielded the most infectious virus (TAN1.910) was identical to the consensus sequence in both protein and long terminal repeat sequences. Two additional SIVcpz clones were constructed by direct synthesis of fecal consensus sequences. One of these (TAN3.1) yielded fully infectious virus, while the second one (TAN2.69) required modification at one ambiguous site in the viral pol gene for biological activity. All three reconstructed proviruses produced infectious virions that replicated in human and chimpanzee CD4+ T cells, were CCR5 tropic, and resembled primary human immunodeficiency virus type 1 isolates in their neutralization phenotype. These results provide the first direct evidence that naturally occurring SIVcpz strains already have many of the biological properties required for persistent infection of humans, including CD4 and CCR5 dependence and neutralization resistance. Moreover, they outline a new strategy for obtaining medically important “SIV isolates” that have thus far eluded investigation. Such isolates are needed to identify viral determinants that contribute to cross-species transmission and host adaptation. PMID:17494082

Takehisa, Jun; Kraus, Matthias H.; Decker, Julie M.; Li, Yingying; Keele, Brandon F.; Bibollet-Ruche, Fréderic; Zammit, Kenneth P.; Weng, Zhiping; Santiago, Mario L.; Kamenya, Shadrack; Wilson, Michael L.; Pusey, Anne E.; Bailes, Elizabeth; Sharp, Paul M.; Shaw, George M.; Hahn, Beatrice H.

2007-01-01

158

Neutral particle beam intensity controller  

DOEpatents

A neutral beam intensity controller is provided for a neutral beam generator in which a neutral beam is established by accelerating ions from an ion source into a gas neutralizer. An amplitude modulated, rotating magnetic field is applied to the accelerated ion beam in the gas neutralizer to defocus the resultant neutral beam in a controlled manner to achieve intensity control of the neutral beam along the beam axis at constant beam energy. The rotating magnetic field alters the orbits of ions in the gas neutralizer before they are neutralized, thereby controlling the fraction of neutral particles transmitted out of the neutralizer along the central beam axis to a fusion device or the like. The altered path or defocused neutral particles are sprayed onto an actively cooled beam dump disposed perpendicular to the neutral beam axis and having a central open for passage of the focused beam at the central axis of the beamline. Virtually zero therough 100% intensity control is achieved by varying the magnetic field strength without altering the ion source beam intensity or its species yield.

Dagenhart, William K. (Oak Ridge, TN)

1986-01-01

159

Four families with immunodeficiency and chromosome abnormalities.  

PubMed Central

Six children, with severe deficiency of some or all of the immunoglobulins and minor somatic abnormalities, had chromosomal abnormalities: (1) 45,XY,t(13q/18q), (2) 46,XY,21ps +, (3) two brothers 46,XY (inv. 7) (4) 45,X,t(11p/10p)/46X,iXq,t(11p/10p) and, (5) in addendum, 45,XX,-18;46,XX, r18. The chromosome abnormalities were detected in B- as well as T-lymphocytes (as evidenced by using both PHA- and PWM-stimulated cultures) in all probands, but one was mosaic in PHA culture, although all his PWM-stimulated cells were abnormal. Chromosomal variants were also detected in relatives of three and immunodeficiency in relatives of two. Images Fig. 1 Fig. 3 PMID:314782

Candy, D C; Hayward, A R; Hughes, D T; Layward, L; Soothill, J F

1979-01-01

160

The acquired immunodeficiency syndrome in gay men.  

PubMed

The acquired immunodeficiency syndrome (AIDS) is a major health problem for gay men in the United States. About three fourths of all reported cases have occurred in this population, and the number is projected to double in the next year. In Manhattan and San Francisco, AIDS is now the leading cause of premature mortality in men aged 25 to 44 years who have never married. In a sample of a cohort of gay men enrolled in a San Francisco clinic, 2.7% of the men had the syndrome and 26% had related conditions in 1984. Antibody to human T-lymphotropic virus, type III/lymphadenopathy-associated virus was found in sera from 67% of the men, including 58% of asymptomatic men. Behavioral factors associated with an increased risk of AIDS include large numbers of sexual partners, receptive anal intercourse, and "fisting." The adoption of safer lifestyles is currently the basis of attempts to control the syndrome in gay men. PMID:2996396

Jaffe, H W; Hardy, A M; Morgan, W M; Darrow, W W

1985-11-01

161

Human immunodeficiency virus infection and the liver  

PubMed Central

Liver disease in human immunodeficiency virus (HIV)-infected individuals encompasses the spectrum from abnormal liver function tests, liver decompensation, with and without evidence of cirrhosis on biopsy, to non-alcoholic liver disease and its more severe form, non-alcoholic steatohepatitis and hepatocellular cancer. HIV can infect multiple cells in the liver, leading to enhanced intrahepatic apoptosis, activation and fibrosis. HIV can also alter gastro-intestinal tract permeability, leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function. This review focuses on recent changes in the epidemiology, pathogenesis and clinical presentation of liver disease in HIV-infected patients, in the absence of co-infection with hepatitis B virus or hepatitis C virus, with a specific focus on issues relevant to low and middle income countries. PMID:22489261

Crane, Megan; Iser, David; Lewin, Sharon R

2012-01-01

162

Prevention of infections during primary immunodeficiency.  

PubMed

Because infectious diseases are a major source of morbidity and mortality in the majority of patients with primary immunodeficiencies (PIDs), the application of a prophylactic regimen is often necessary. However, because of the variety of PIDs and pathogens involved, and because evidence is scarce, practices are heterogeneous. To homogenize practices among centers, the French National Reference Center for PIDs aimed at elaborating recommendations for anti-infectious prophylaxis for the most common PIDs. We performed a literature review of infectious complications and prophylactic regimens associated with the most frequent PIDs. Then, a working group including different specialists systematically debated about chemoprophylaxis, immunotherapy, immunization, and recommendations for patients. Grading of prophylaxis was done using strength of recommendations (decreasing from A to D) and evidence level (decreasing from I to III). These might help infectious diseases specialists in the management of PIDs and improving the outcome of patients with PIDs. PMID:25124061

Aguilar, Claire; Malphettes, Marion; Donadieu, Jean; Chandesris, Olivia; Coignard-Biehler, Hélène; Catherinot, Emilie; Pellier, Isabelle; Stephan, Jean-Louis; Le Moing, Vincent; Barlogis, Vincent; Suarez, Felipe; Gérart, Stéphane; Lanternier, Fanny; Jaccard, Arnaud; Consigny, Paul-Henri; Moulin, Florence; Launay, Odile; Lecuit, Marc; Hermine, Olivier; Oksenhendler, Eric; Picard, Capucine; Blanche, Stéphane; Fischer, Alain; Mahlaoui, Nizar; Lortholary, Olivier

2014-11-15

163

Acquired immunodeficiency syndrome: Ga-67 citrate imaging  

SciTech Connect

All gallium-67 citrate scans obtained in patients with acquired immunodeficiency syndrome (AIDS) at the Clinical Center, National Institutes of Health (Bethesda, Md.) were retrospectively analyzed and correlated with the results of bronchoscopy, chest radiography, and endoscopy. There were 164 scans of 95 patients. Twenty scans were from patients with Pneumocystis carinii pneumonia; 19 were abnormal, for a sensitivity of 95%. Ga-67 uptake tended to be less in patients receiving therapy for P. carinii pneumonia. Chest radiographs were normal at least initially in three patients with abnormal scans and P. carinii pneumonia. Unusually prominent colonic activity was associated with infection in some patients. No lesions of Kaposi sarcoma showed tracer uptake. Gallium scanning is useful for detecting P. carinii pneumonia and other opportunistic infections in patients with AIDS, but it is not useful for localizing Kaposi sarcoma.

Woolfenden, J.M.; Carrasquillo, J.A.; Larson, S.M.; Simmons, J.T.; Masur, H.; Smith, P.D.; Shelhamer, J.H.; Ognibene, F.P.

1987-02-01

164

Autoimmune Cytopenias In Common Variable Immunodeficiency  

PubMed Central

Common variable immunodeficiency (CVID) is a humoral immunodeficiency whose primary diagnostic features include hypogammaglobulinemia involving two or more immunoglobulin isotypes and impaired functional antibody responses in the majority of patients. While increased susceptibility to respiratory and other infections is a common thread that binds a large cross-section of CVID patients, the presence of autoimmune complications in this immunologically and clinically heterogeneous disorder is recognized in up to two-thirds of patients. Among the autoimmune manifestations reported in CVID (20–50%; Chapel et al., 2008; Cunningham-Rundles, 2008), autoimmune cytopenias are by far the most common occurring variably in 4–20% (Michel et al., 2004; Chapel et al., 2008) of these patients who have some form of autoimmunity. Association of autoimmune cytopenias with granulomatous disease and splenomegaly has been reported. The spectrum of autoimmune cytopenias includes thrombocytopenia, anemia, and neutropenia. While it may seem paradoxical “prima facie” that autoimmunity is present in patients with primary immune deficiencies, in reality, it could be considered two sides of the same coin, each reflecting a different but inter-connected facet of immune dysregulation. The expansion of CD21 low B cells in CVID patients with autoimmune cytopenias and other autoimmune features has also been previously reported. It has been demonstrated that this unique subset of B cells is enriched for autoreactive germline antibodies. Further, a correlation has been observed between various B cell subsets, such as class-switched memory B cells and plasmablasts, and autoimmunity in CVID. This review attempts to explore the most recent concepts and highlights, along with treatment of autoimmune hematological manifestations of CVID. PMID:22837758

Podjasek, Jenna C.; Abraham, Roshini S.

2012-01-01

165

Neutral Equations of Mixed Type  

E-print Network

In this dissertation we consider neutral equations of mixed type. In particular, we con- sider the associated linear Fredholm theory and nerve fiber models that are written as systems of neutral equations of mixed type. In Chapter 2, we extend...

Lamb, Charles

2012-12-31

166

Neutral particle beam intensity controller  

DOEpatents

The neutral beam intensity controller is based on selected magnetic defocusing of the ion beam prior to neutralization. The defocused portion of the beam is dumped onto a beam dump disposed perpendicular to the beam axis. Selective defocusing is accomplished by means of a magnetic field generator disposed about the neutralizer so that the field is transverse to the beam axis. The magnetic field intensity is varied to provide the selected partial beam defocusing of the ions prior to neutralization. The desired focused neutral beam portion passes along the beam path through a defining aperture in the beam dump, thereby controlling the desired fraction of neutral particles transmitted to a utilization device without altering the kinetic energy level of the desired neutral particle fraction. By proper selection of the magnetic field intensity, virtually zero through 100% intensity control of the neutral beam is achieved.

Dagenhart, W.K.

1984-05-29

167

Between detection and neutralization.  

SciTech Connect

Security system analytical performance analysis is generally based on the probability of system effectiveness. The probability of effectiveness is a function of the probabilities of interruption and neutralization. Interruption occurs if the response forces are notified in sufficient time to engage the adversary. Neutralization occurs if the adversary attack is defeated after the security forces have actively engaged the adversary. Both depend upon communications of data. This paper explores details of embedded communications functions that are often assumed to be inconsequential. It is the intent of the authors to bring focus to an issue in security system modeling that, if not well understood, has the potential to be a deciding factor in the overall system failure or effectiveness.

Snell, Mark Kamerer; Green, Mary Wilson; Adams, Douglas Glenn; Pritchard, Daniel Allison

2005-08-01

168

Envelope Variants Circulating as Initial Neutralization Breadth Developed in Two HIV-Infected Subjects Stimulate Multiclade Neutralizing Antibodies in Rabbits  

PubMed Central

ABSTRACT Identifying characteristics of the human immunodeficiency virus type 1 (HIV-1) envelope that are effective in generating broad, protective antibodies remains a hurdle to HIV vaccine design. Emerging evidence of the development of broad and potent neutralizing antibodies in HIV-infected subjects suggests that founder and subsequent progeny viruses may express unique antigenic motifs that contribute to this developmental pathway. We hypothesize that over the course of natural infection, B cells are programmed to develop broad antibodies by exposure to select populations of emerging envelope quasispecies variants. To test this hypothesis, we identified two unrelated subjects whose antibodies demonstrated increasing neutralization breadth against a panel of HIV-1 isolates over time. Full-length functional env genes were cloned longitudinally from these subjects from months after infection through 2.6 to 5.8 years of infection. Motifs associated with the development of breadth in published, cross-sectional studies were found in both subjects. We compared the immunogenicity of envelope vaccines derived from time points obtained during and after broadening of neutralization activity within these subjects. Rabbits were coimmunized four times with selected multiple gp160 DNAs and gp140-trimeric envelope proteins. The affinity of the polyclonal response increased as a function of boosting. The most rapid and persistent neutralization of multiclade tier 1 viruses was elicited by envelopes that were circulating in plasma at time points prior to the development of 50% neutralization breadth in both human subjects. The breadth elicited in rabbits was not improved by exposure to later envelope variants. These data have implications for vaccine development in describing a target time point to identify optimal envelope immunogens. IMPORTANCE Vaccine protection against viral infections correlates with the presence of neutralizing antibodies; thus, vaccine components capable of generating potent neutralization are likely to be critical constituents in an effective HIV vaccine. However, vaccines tested thus far have elicited only weak antibody responses and very modest, waning protection. We hypothesized that B cells develop broad antibodies by exposure to the evolving viral envelope population and tested this concept using multiple envelopes from two subjects who developed neutralization breadth within a few years of infection. We compared different combinations of envelopes from each subject to identify the most effective immunogens and regimens. In each subject, use of HIV envelopes circulating during the early development and maturation of breadth generated more-potent antibodies that were modestly cross neutralizing. These data suggest a new approach to identifying envelope immunogens that may be more effective in generating protective antibodies in humans. PMID:25210191

Malherbe, Delphine C.; Pissani, Franco; Sather, D. Noah; Guo, Biwei; Pandey, Shilpi; Sutton, William F.; Stuart, Andrew B.; Robins, Harlan; Park, Byung; Krebs, Shelly J.; Schuman, Jason T.; Kalams, Spyros; Hessell, Ann J.

2014-01-01

169

Antihypertensive neutral lipid  

DOEpatents

The invention relates to the discovery of a class of neutral acetylated ether-linked glycerolipids having the capacity to lower blood pressure in warm-blooded animals. This physiological effect is structure sensitive requiring a long chain alkyl group at the sn-1 position and a short carbon chain acyl group (acetyl or propionyl) at the sn-2 position, and a hydroxyl group at the sn-3 position.

Snyder, Fred L. (Oak Ridge, TN); Blank, Merle L. (Oak Ridge, TN)

1986-01-01

170

Antihypertensive neutral lipid  

DOEpatents

The invention relates to the discovery of a class of neutral acetylated either-linked glycerolipids having the capacity to lower blood presure in warm-blooded animals. This physiological effect is structure sensitive requiring a long chain alkyl group at the sn-1 position and a short carbon chain acyl group (acetyl or propionyl) at the sn-2 position, and a hydroxyl group at the sn-3 position.

Snyder, F.L.; Blank, M.L.

1984-10-26

171

Neutral atom traps.  

SciTech Connect

This report describes progress in designing a neutral atom trap capable of trapping sub millikelvin atom in a magnetic trap and shuttling the atoms across the atom chip from a collection area to an optical cavity. The numerical simulation and atom chip design are discussed. Also, discussed are preliminary calculations of quantum noise sources in Kerr nonlinear optics measurements based on electromagnetically induced transparency. These types of measurements may be important for quantum nondemolition measurements at the few photon limit.

Pack, Michael Vern

2008-12-01

172

Neutrality between Government and Religion.  

ERIC Educational Resources Information Center

The overall guiding principle of neutrality between government and religion masks a tension that exists between free exercise of religion and establishment of religion. Reviews the development and current status of "Lemon" as a test for neutrality; proposes a new test for neutrality, evenhandedness, that is common to both the Free Exercise and…

Mawdsley, Ralph D.

1996-01-01

173

Building networks for immunodeficiency diseases and immunology training.  

PubMed

The RIKEN Research Center for Allergy and Immunology in Japan is reaching out regionally to the primary immunodeficiency disease community and internationally to graduate students and postdoctoral fellows. PMID:18711439

Burrows, Peter D; Fischer, Alain

2008-09-01

174

[Skin symptoms associated with human immunodeficiency virus infection].  

PubMed

The recently observed accelerated increase of human immunodeficiency virus infection in Hungary poses a major public concern for the healthcare system. Given the effective only but not the curative therapy, prevention should be emphasized. Current statistics estimate that about 50% of the infected persons are not aware of their human immunodeficiency virus-positivity. Thus, early diagnosis of the infection by serological screening and timely recognition of the disease-associated symptoms are crucial. The authors' intention is to facilitate early infection detection with this review on human immunodeficiency virus-associated skin symptoms, and highlight the significance of human immunodeficiency virus care in the everyday medical practice. Orv. Hetil., 2015, 156(1), 10-18. PMID:25544049

Tamási, Béla; Marschalkó, Márta; Kárpáti, Sarolta

2015-01-01

175

Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01  

SciTech Connect

During HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1. Among these antibodies, VRC01 achieves broad neutralization of diverse viral strains. We determined the crystal structure of VRC01 in complex with a human immunodeficiency virus HIV-1 gp120 core. VRC01 partially mimics CD4 interaction with gp120. A shift from the CD4-defined orientation, however, focuses VRC01 onto the vulnerable site of initial CD4 attachment, allowing it to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. To achieve this recognition, VRC01 contacts gp120 mainly through immunoglobulin V-gene regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies.

Zhou, Tongqing; Georgiev, Ivelin; Wu, Xueling; Yang, Zhi-Yong; Dai, Kaifan; Finzi, Andrés; Kwon, Young Do; Scheid, Johannes F.; Shi, Wei; Xu, Ling; Yang, Yongping; Zhu, Jiang; Nussenzweig, Michel C.; Sodroski, Joseph; Shapiro, Lawrence; Nabel, Gary J.; Mascola, John R.; Kwong, Peter D. (NIH); (Rockefeller); (DFCI)

2010-08-26

176

Human immunodeficiency viruses: SIV infection in wild gorillas  

Microsoft Academic Search

Chimpanzees (Pan troglodytes troglodytes) from west central Africa are recognized as the reservoir of simian immunodeficiency viruses (SIVcpzPtt) that have crossed at least twice to humans: this resulted in the AIDS pandemic (from human immunodeficiency virus HIV-1 group M) in one instance and infection of just a few individuals in Cameroon (by HIV-1 group N) in another. A third HIV-1

Fran van Heuverswyn; Yingying Li; Cecile Neel; Elizabeth Bailes; Brandon F. Keele; Weimin Liu; Severin Loul; Christelle Butel; Florian Liegeois; Yanga Bienvenue; Eitel Mpoudi Ngolle; Paul M. Sharp; George M. Shaw; Eric Delaporte; Beatrice H. Hahn; Martine Peeters

2006-01-01

177

Intestinal mucosal inflammation associated with human immunodeficiency virus infection  

Microsoft Academic Search

The role of the human immunodeficiency virus type-1 (HIV) in producing intestinal disease was studied prospectively in 74 HIV-infected individuals with (43) or without (31) the acquired immunodeficiency syndrome (AIDS). Thirty-one subjects had enteric infections; all but one had AIDS. Alteration in bowell habits was the most common symptom and occurred independently of enteric infections. Abnormal histopathology was present in

Donald P. Kotler; Safak Reka; Frederic Clayton

1993-01-01

178

CD4-Mimetic Small Molecules Sensitize Human Immunodeficiency Virus to Vaccine-Elicited Antibodies  

PubMed Central

ABSTRACT Approaches to prevent human immunodeficiency virus (HIV-1) transmission are urgently needed. Difficulties in eliciting antibodies that bind conserved epitopes exposed on the unliganded conformation of the HIV-1 envelope glycoprotein (Env) trimer represent barriers to vaccine development. During HIV-1 entry, binding of the gp120 Env to the initial receptor, CD4, triggers conformational changes in Env that result in the formation and exposure of the highly conserved gp120 site for interaction with the coreceptors, CCR5 and CXCR4. The DMJ compounds (+)-DMJ-I-228 and (+)-DMJ-II-121 bind gp120 within the conserved Phe 43 cavity near the CD4-binding site, block CD4 binding, and inhibit HIV-1 infection. Here we show that the DMJ compounds sensitize primary HIV-1, including transmitted/founder viruses, to neutralization by monoclonal antibodies directed against CD4-induced (CD4i) epitopes and the V3 region, two gp120 elements involved in coreceptor binding. Importantly, the DMJ compounds rendered primary HIV-1 sensitive to neutralization by antisera elicited by immunization of rabbits with HIV-1 gp120 cores engineered to assume the CD4-bound state. Thus, small molecules like the DMJ compounds may be useful as microbicides to inhibit HIV-1 infection directly and to sensitize primary HIV-1 to neutralization by readily elicited antibodies. IMPORTANCE Preventing HIV-1 transmission is a priority for global health. Eliciting antibodies that can neutralize many different strains of HIV-1 is difficult, creating problems for the development of a vaccine. We found that certain small-molecule compounds can sensitize HIV-1 to particular antibodies. These antibodies can be elicited in rabbits. These results suggest an approach to prevent HIV-1 sexual transmission in which a virus-sensitizing microbicide is combined with a vaccine. PMID:24696475

Madani, Navid; Princiotto, Amy M.; Schön, Arne; LaLonde, Judith; Feng, Yu; Freire, Ernesto; Park, Jongwoo; Courter, Joel R.; Jones, David M.; Robinson, James; Liao, Hua-Xin; Moody, M. Anthony; Permar, Sallie; Haynes, Barton; Smith, Amos B.; Wyatt, Richard

2014-01-01

179

Osteoarticular infectious complications in patients with primary immunodeficiencies  

PubMed Central

Purpose of review To describe the incidence and management of various infectious arthritides in selected primary immunodeficiency states. Recent findings Joint complications have been a well recognized finding in patients with primary immunodeficiencies for many years. Many are clearly infectious in etiology, but other apparently noninfectious joint abnormalities similar to rheumatoid arthritis have been shown to be due to an underlying infectious trigger. In humoral immunodeficiencies such as common variable immunodeficiency and X-linked agammaglobulinemia, bacterial organisms are the most common causes of infectious arthritis, but mycoplasmas and ureaplasmas are also of particular importance. In nonhumoral immunodeficiencies, noninfectious inflammatory arthritides are more prevalent, although microbiologic organisms have been reported in some cases of arthritis. Lack of appropriate culturing techniques and documentation of infectious agents may underestimate the prevalence of low-virulence infections in these patients. Summary Infectious arthritis is a significant comorbidity associated with primary immunodeficiencies and can be the presenting feature for some patients. Prompt examination for common as well as atypical organisms is not only important for the treatment but also crucial to the understanding of the exact etiology of arthritides as a whole in these disorders. PMID:18525364

Bloom, Katherine A.; Chung, Danna; Cunningham-Rundles, Charlotte

2008-01-01

180

Inhibition of human immunodeficiency virus type 1 (HIV-1) nuclear import via Vpr-Importin {alpha} interactions as a novel HIV-1 therapy  

SciTech Connect

The development of multidrug-resistant viruses compromises the efficacy of anti-human immunodeficiency virus (HIV) therapy and limits treatment options. Therefore, new targets that can be used to develop novel antiviral agents need to be identified. One such target is the interaction between Vpr, one of the accessory gene products of HIV-1 and Importin {alpha}, which is crucial, not only for the nuclear import of Vpr, but also for HIV-1 replication in macrophages. We have identified a potential parent compound, hematoxylin, which suppresses Vpr-Importin {alpha} interaction, thereby inhibiting HIV-1 replication in a Vpr-dependent manner. Analysis by real-time PCR demonstrated that hematoxylin specifically inhibited nuclear import step of pre-integration complex. Thus, hematoxylin is a new anti-HIV-1 inhibitor that targets the nuclear import of HIV-1 via the Vpr-Importin {alpha} interaction, suggesting that a specific inhibitor of the interaction between viral protein and the cellular factor may provide a new strategy for HIV-1 therapy.

Suzuki, Tatsunori [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Yamamoto, Norio [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Department of General Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Nonaka, Mizuho; Hashimoto, Yoshie; Matsuda, Go; Takeshima, Shin-nosuke [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Matsuyama, Megumi; Igarashi, Tatsuhiko; Miura, Tomoyuki [Institute for Virus Research, Kyoto University, Kyoto 606-8507 (Japan); Tanaka, Rie; Kato, Shingo [Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo 160-8582 (Japan); Aida, Yoko [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)], E-mail: aida@riken.jp

2009-03-20

181

Frequency and Clinical Manifestations of Patients with Primary Immunodeficiency Disorders in Iran: Update from the Iranian Primary Immunodeficiency Registry  

Microsoft Academic Search

Primary immunodeficiency disorders (PID) are a heterogeneous group of diseases, characterized by an increased susceptibility to infections. A total of 930 patients (573 males and 357 females) are registered in Iranian PID Registry (IPIDR) during three decades. Predominantly antibody deficiencies were the most common (38.4%), followed by congenital defects of phagocyte number and\\/or function (28.3%), other well-defined immunodeficiency syndromes (17.7%),

NIMA REZAEI; ASGHAR AGHAMOHAMMADI; MOSTAFA MOIN; ZAHRA POURPAK; MASOUD MOVAHEDI; MOHAMMAD GHARAGOZLOU; LIDA ATAROD; BAHRAM MIRSAEID GHAZI; ANNA ISAEIAN; MARYAM MAHMOUDI; KAMRAN ABOLMAALI; DAVOUD MANSOURI; SABA ARSHI; NASER JAVAHER TARASH; ROYA SHERKAT; HEDAYAT AKBARI; REZA AMIN; ABDOLVAHAB ALBORZI; SARA KASHEF; REZA FARID; IRAJ MOHAMMADZADEH; MEHRNAZ SADEGHI SHABESTARI; MOHAMMAD NABAVI; ABOLHASSAN FARHOUDI

2006-01-01

182

A Pathogenic Threshold of Virus Load Defined in Simian Immunodeficiency Virus or Simian-Human Immunodeficiency VirusInfected Macaques  

Microsoft Academic Search

To determine if a specific pathogenic threshold of plasma viral RNA could be defined irrespective of virus strain, RNA levels in the plasma of more than 50 infected rhesus macaques (Macaca mulatta) were measured. Animals were inoculated intravenously with either simian immunodeficiency virus (SIV) or simian-human immunodeficiency virus (SHIV) strains of known pathogenic potential (SIV8980, SIVsmm-3, SIVmac32H\\/J5, SIVmac32H\\/1XC, reverse transcriptase-SHIV,

PETER TEN HAAFT; BABS VERSTREPEN; KLAUS UBERLA; BRIGITTE ROSENWIRTH; JONATHAN HEENEY

1998-01-01

183

CD4+ and CD8+ cells accumulate in the brains of acquired immunodeficiency syndrome patients with human immunodeficiency virus encephalitis  

Microsoft Academic Search

To test the hypothesis that CD4+ T lymphocytes accumulate in brains of end-stage acquired immunodeficiency syndrome (AIDS)\\u000a patients, we examined T-lymphocyte subsets in the CA1, CA3, and CA4 regions of the hippocampus of AIDS patients with (n = 10) and without (n = 11) human immunodeficiency virus encephalitis (HIVE) plus controls (n = 7). HIV p24 antigen was common in

C. K. Petito; B. Adkins; M. McCarthy; B. Roberts; I. Khamis

2003-01-01

184

Neutral beam injection system  

SciTech Connect

The development of the neutral injection (NI) system for the Joint European Torus and its status in 1985 are reported. First the system parameters are discussed and the layout is described, followed by a summary of the physics design calculations, the development, production, and testing of the components and the subsystem assembly. The system commissioning is presented, including a description of the function and the realization of the NI test bed. A summary of performance predictions for 80-keV beam heating experiments, and of the experimental evidence on balanced versus coinjection, is presented. The operational experience with the first injector and the plasma physics results obtained so far are summarized.

Duesing, G.; Altmann, H.; Falter, H.; Goede, A.; Haange, R.; Hemsworth, R.S.; Kupschus, P.; Stork, D.; Thompson, E.

1987-01-01

185

The Neonatal Fc Receptor (FcRn) Enhances Human Immunodeficiency Virus Type 1 (HIV-1) Transcytosis across Epithelial Cells  

PubMed Central

The mechanisms by which human immunodeficiency virus type 1 (HIV-1) crosses mucosal surfaces to establish infection are unknown. Acidic genital secretions of HIV-1-infected women contain HIV-1 likely coated by antibody. We found that the combination of acidic pH and Env-specific IgG, including that from cervicovaginal and seminal fluids of HIV-1-infected individuals, augmented transcytosis across epithelial cells as much as 20-fold compared with Env-specific IgG at neutral pH or non-specific IgG at either pH. Enhanced transcytosis was observed with clinical HIV-1 isolates, including transmitted/founder strains, and was eliminated in Fc neonatal receptor (FcRn)-knockdown epithelial cells. Non-neutralizing antibodies allowed similar or less transcytosis than neutralizing antibodies. However, the ratio of total:infectious virus was higher for neutralizing antibodies, indicating that they allowed transcytosis while blocking infectivity of transcytosed virus. Immunocytochemistry revealed abundant FcRn expression in columnar epithelia lining the human endocervix and penile urethra. Acidity and Env-specific IgG enhance transcytosis of virus across epithelial cells via FcRn and could facilitate translocation of virus to susceptible target cells following sexual exposure. PMID:24278022

Gupta, Sandeep; Gach, Johannes S.; Becerra, Juan C.; Phan, Tran B.; Pudney, Jeffrey; Moldoveanu, Zina; Joseph, Sarah B.; Landucci, Gary; Supnet, Medalyn Jude; Ping, Li-Hua; Corti, Davide; Moldt, Brian; Hel, Zdenek; Lanzavecchia, Antonio; Ruprecht, Ruth M.; Burton, Dennis R.; Mestecky, Jiri; Anderson, Deborah J.; Forthal, Donald N.

2013-01-01

186

Epitope Specificity of Human Immunodeficiency Virus-1 Antibody Dependent Cellular Cytotoxicity [ADCC] Responses  

PubMed Central

Antibody dependent cellular cytotoxicity [ADCC] has been suggested to play an important role in control of Human Immunodeficiency Virus-1 [HIV-1] viral load and protection from infection. ADCC antibody responses have been mapped to multiple linear and conformational epitopes within the HIV-1 envelope glycoproteins gp120 and gp41. Many epitopes targeted by antibodies that mediate ADCC overlap with those recognized by antibodies capable of virus neutralization. In addition, recent studies conducted with human monoclonal antibodies derived from HIV-1 infected individuals and HIV-1 vaccine-candidate vaccinees have identified a number of antibodies that lack the ability to capture primary HIV-1 isolates or mediate neutralizing activity, but are able to bind to the surface of infected CD4+ T cells and mediate ADCC. Of note, the conformational changes in the gp120 that may not exclusively relate to binding of the CD4 molecule are important in exposing epitopes recognized by ADCC responses. Here we discuss the HIV-1 envelope epitopes targeted by ADCC antibodies in the context of the potential protective capacities of ADCC. PMID:24191939

Pollara, Justin; Bonsignori, Mattia; Moody, M. Anthony; Pazgier, Marzena; Haynes, Barton F; Ferrari, Guido

2013-01-01

187

Viral multiplicity of attachment and its implications for human immunodeficiency virus therapies.  

PubMed Central

The multiplicity of attachment (MOA) of a virion in any particular time interval is the average number of cellular attachment opportunities that must be blocked to keep the virion in suspension. MOA is usually proportional to incubation time and cell concentration. Low MOA (like low multiplicity of infection) is required for reproducible assay of adsorptive blockers, and high MOA by itself can produce spurious synergies between adsorptive blockers, e.g., soluble CD4 (sCD4) and some antibodies. Poliovirus and human immunodeficiency virus (HIV) data show that viral neutralization conforms quantitatively to MOA and kinetic theory over large ranges of incubation times and target cell concentrations. Extrapolating sCD4 data beyond conditions achievable in vitro to those in vivo predicts that sCD4 concentrations above the strain-specific sCD4-gp120 dissociation constant are required to block lymphoid HIV significantly, in at least semiquantitative agreement with clinical results. The extrapolation is applicable to humoral neutralization data as well. MOA analysis also indicates that although completely stopping the attachment of individual virions to cells may still be an effective therapeutic strategy against established HIV infection, merely retarding attachment probably is not. The concept of MOA holds great promise for improving the therapeutic relevance of in vitro data and can be applied to any infectious agent, to many processes that impair or enhance infection steps, and to many assay end points, not just infection. PMID:8107240

Spouge, J L

1994-01-01

188

Feline immunodeficiency virus vaccination: characterization of the immune correlates of protection.  

PubMed Central

Whole inactivated virus (WIV) vaccines derived from the FL4 cell line protect cats against challenge with feline immunodeficiency virus (FIV). To investigate the correlates of protective immunity induced by WIV, we established an immunization regimen which protected a proportion of the vaccinates against challenge. A strong correlation was observed between high virus neutralizing antibody titers and protection following challenge. To investigate further the immune mechanisms responsible for immunity, all of the vaccinates were rechallenged 35 weeks following the initial challenge. Results of virus isolation from peripheral blood mononuclear cells indicated that 9 of 10 vaccinates were protected from viremia following the second challenge, suggesting that vaccine-induced immunity to FIV persisted for at least 8 months. However, more stringent analysis for evidence of infection revealed that 5 of 10 vaccinates harbored virus in lymphoid tissues. Unlike the protection observed immediately following vaccination, which correlated positively with virus neutralizing antibody titer, the ability to resist a second challenge with FIV was more closely correlated with the induction of Env-specific cytotoxic T-cell activity. The results indicate that both virus-specific humoral immunity and cellular immunity play a role in the protection induced in cats by WIV immunization but their relative importance may be dependent on the interval between vaccination and exposure to virus. PMID:8892875

Hosie, M J; Flynn, J N

1996-01-01

189

Primary immunodeficiencies of the B Lymphocyte  

PubMed Central

The immune response consists of two main components: humoral immunity represented by B lymphocytes and cellular immunity maintained by the T lymphocytes. Immunoglobulins, produced by B– lymphocytes, are the main mediators of humoral immunity, and deficiencies at this level affect the body's response to infection. Plasmocytes produce nine antibody izotypes: immunoglobulins G (IgG 1, lgG2, lgG3, lgG4), immunoglobulins M (IgM), immunoglobulins A (lgA1, lgA2), immunoglobulins D (IGD) and immunoglobulins E (IgE). Primary hypogammaglobulinemias are characterized by the occurrence of recurrent infections and, paradoxically, by the occurrence of autoimmune diseases. Characteristic for these diseases is that symptoms occur at 7–9 months after birth, when transplacental antibody titers transmitted from the mother decrease, and the infant's body is unable to synthesize them to normal levels. Primary hypogammaglobulinemias are transmitted genetically, but mutations at the molecular level are still not fully understood. The most common are: Bruton agammaglobulinemia , transient newborn hypogammaglobulinemia, selective immunoglobulin deficiency and variable common immunodeficiency. Treatment consists of monthly antibiotics and immunoglobulins, depending on antibody titers (except for IgA deficiency). PMID:20302197

Moise, A; Nedelcu, FA; Toader, MA; Sora, SM; Tica, A; Ferastraoaru, DE; Constantinescu, I

2010-01-01

190

Immunodeficiency and laser magnetic therapy in urology  

NASA Astrophysics Data System (ADS)

The importance of immunodeficiency problem has increased last time not only due to AIDS appearance, but also to a great extent as a result of the development and active practical use of the methods of immunology parameters investigations. Al great pharmaceutical firms are organizing the process of creating the drugs, influencing on the different phases of immunity, but unfortunately, the problem of their adverse effect and connected complications is till today a milestone. A great number of investigations, proving a good effect of laser-magnetic therapy concerning immune system have been done today. There is, in particular, changing of blood counts and immunologic tests after intravenous laser irradiation of blood. Intravenous laser irradiation of blood results in increasing of lymphocytes, T-immuno stimulation, stabilization of t-lymphocyte subpopulation, increasing of t-lymphocyte helper activity and decreasing of suppressor one.Under this laser action number of circulating immune complexes is decreased, and blood serum bactericide activity and lisozyme number are increased.

Maati, Moufagued; Rozanov, Vladimir V.; Avdoshin, V. P.

1996-11-01

191

Antiviral therapy for human immunodeficiency virus infections.  

PubMed Central

Depending on the stage of their intervention with the viral replicative cycle, human immunodeficiency virus inhibitors could be divided into the following groups: (i) adsorption inhibitors (i.e., CD4 constructs, polysulfates, polysulfonates, polycarboxylates, and polyoxometalates), (ii) fusion inhibitors (i.e., plant lectins, succinylated or aconitylated albumins, and betulinic acid derivatives), (iii) uncoating inhibitors (i.e., bicyclams), (iv) reverse transcription inhibitors acting either competitively with the substrate binding site (i.e., dideoxynucleoside analogs and acyclic nucleoside phosphonates) or allosterically with a nonsubstrate binding site (i.e., non-nucleoside reverse transcriptase inhibitors), (v) integration inhibitors, (vi) DNA replication inhibitors, (vii) transcription inhibitors (i.e., antisense oligodeoxynucleotides and Tat antagonists), (viii) translation inhibitors (i.e., antisense oligodeoxynucleotides and ribozymes), (ix) maturation inhibitors (i.e., protease inhibitors, myristoylation inhibitors, and glycosylation inhibitors), and finally, (x) budding (assembly/release) inhibitors. Current knowledge, including the therapeutic potential, of these various inhibitors is discussed. In view of their potential clinical the utility, the problem of virus-drug resistance and possible strategies to circumvent this problem are also addressed. PMID:7542558

De Clercq, E

1995-01-01

192

Bone health and human immunodeficiency virus infection.  

PubMed

Low bone mineral density is common among persons with human immunodeficiency virus (HIV) infection, and studies reporting increased fracture rates in this patient population are emerging. The causes of low bone mineral density, osteoporosis, and fractures in persons with HIV are likely multifactorial, involving traditional risk factors, HIV infection, and exposure to antiretroviral treatment. Specific antiretrovirals such as tenofovir may cause a greater loss of bone mineral density compared with other agents and have recently been linked to an increased risk for fracture. As a result, recent treatment guidelines suggest that clinicians consider avoiding tenofovir as initial therapy in postmenopausal women. Evaluating bone mineral density and vitamin D status in persons with HIV may be important steps in identifying those requiring pharmacotherapy; however, the appropriate timing for bone mineral density and vitamin D screening is uncertain, as is the appropriate method of replacing vitamin D in HIV-positive patients who are deficient. Further study is necessary to definitively determine the approach to evaluating bone health and managing low bone mineral density and vitamin D deficiency in patients with HIV infection. PMID:23553497

Schafer, Jason J; Manlangit, Kristine; Squires, Kathleen E

2013-06-01

193

Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus.  

PubMed

Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide a blueprint for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. The mature antibody, CH103, neutralized approximately 55% of HIV-1 isolates, and its co-crystal structure with the HIV-1 envelope protein gp120 revealed a new loop-based mechanism of CD4-binding-site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the unmutated common ancestor of the CH103 lineage avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data determine the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies, and provide insights into strategies to elicit similar antibodies by vaccination. PMID:23552890

Liao, Hua-Xin; Lynch, Rebecca; Zhou, Tongqing; Gao, Feng; Alam, S Munir; Boyd, Scott D; Fire, Andrew Z; Roskin, Krishna M; Schramm, Chaim A; Zhang, Zhenhai; Zhu, Jiang; Shapiro, Lawrence; Mullikin, James C; Gnanakaran, S; Hraber, Peter; Wiehe, Kevin; Kelsoe, Garnett; Yang, Guang; Xia, Shi-Mao; Montefiori, David C; Parks, Robert; Lloyd, Krissey E; Scearce, Richard M; Soderberg, Kelly A; Cohen, Myron; Kamanga, Gift; Louder, Mark K; Tran, Lillian M; Chen, Yue; Cai, Fangping; Chen, Sheri; Moquin, Stephanie; Du, Xiulian; Joyce, M Gordon; Srivatsan, Sanjay; Zhang, Baoshan; Zheng, Anqi; Shaw, George M; Hahn, Beatrice H; Kepler, Thomas B; Korber, Bette T M; Kwong, Peter D; Mascola, John R; Haynes, Barton F

2013-04-25

194

Prevention and treatment of human immunodeficiency virus/acquired immunodeficiency syndrome in resource-limited settings.  

PubMed Central

Strategies for confronting the epidemic of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) have included a range of different approaches that focus on prevention and treatment. However, debate persists over what levels of emphasis are appropriate for the different components of the global response. This paper presents an overview of this debate and briefly summarizes the evidence on a range of interventions designed to prevent the spread of HIV infection, paying particular attention to voluntary counselling and testing, treatment for sexually transmitted infections and prevention of mother-to-child transmission. We also review the experience with antiretroviral therapy to date in terms of response rates and survival rates, adherence, drug resistance, behavioural change and epidemiological impact. Although various studies have identified strategies with proven effectiveness in reducing the risks of HIV infection and AIDS mortality, considerable uncertainties remain. Successful integration of treatment and prevention of HIV/AIDS will require a balanced approach and rigorous monitoring of the impact of programmes in terms of both individual and population outcomes. PMID:15744406

Hogan, Daniel R.; Salomon, Joshua A.

2005-01-01

195

Neutral evolution of mutational robustness  

PubMed Central

We introduce and analyze a general model of a population evolving over a network of selectively neutral genotypes. We show that the population’s limit distribution on the neutral network is solely determined by the network topology and given by the principal eigenvector of the network’s adjacency matrix. Moreover, the average number of neutral mutant neighbors per individual is given by the matrix spectral radius. These results quantify the extent to which populations evolve mutational robustness—the insensitivity of the phenotype to mutations—and thus reduce genetic load. Because the average neutrality is independent of evolutionary parameters—such as mutation rate, population size, and selective advantage—one can infer global statistics of neutral network topology by using simple population data available from in vitro or in vivo evolution. Populations evolving on neutral networks of RNA secondary structures show excellent agreement with our theoretical predictions. PMID:10449760

van Nimwegen, Erik; Crutchfield, James P.; Huynen, Martijn

1999-01-01

196

Primary immunodeficiency diseases: a 30-year patient registry from the referral center for primary immunodeficiencies in Greece.  

PubMed

Primary Immunodeficiencies (PID) represent a group of heterogeneous immune diseases with important biological significance. We reviewed the records of children diagnosed with PID in the Referral Center for PID in our country in order to describe the epidemiological, clinical and laboratory characteristics of immunodeficient patients. During a 30-year period, 147 patients (101 males, 68.7 %), with a mean age of 6.5 years at the time of diagnosis, were diagnosed with PID. The most prevalent diagnoses of PID were: "Combined Immunodeficiency" in 46 (31.3 %) patients, "Well-defined immunodeficiency syndrome" in 35 (23.1 %) patients, "Predominantly antibody deficiency" in 30 (20.4 %) patients and "Congenital defect of phagocyte function or both" in 28 (19 %) patients. There was a higher prevalence of males with "Combined immunodeficiency" (p?immunodeficiency" [median 0.3y (IQR: 0.1-1)], and longer for those with "Predominantly antibody deficiency" [median 3.2y (IQR: 0.2-5.9) or "Disease of immune dysregulation" [median 3.2y (IQR: 0.1-6.6)]. Comparing the rates in our population with those of the European Registry (ESID), the rates of "Combined immunodeficiencies", "Well-defined syndromes" and "Congenital birth defects and/or function of phagocytes" were significantly higher in this study (p <0,001). PID registry analysis improves knowledge in the field of Immunology and enhances awareness, early detection, diagnosis, and management of this rare but significant group of diseases. PMID:24981038

Michos, Athanasios; Raptaki, Maria; Tantou, Sofia; Tzanoudaki, Marianna; Spanou, Kleopatra; Liatsis, Manolis; Constantinidou, Nikki; Paschali, Evangelia; Varela, Ioanna; Moraloglou, Olga; Bakoula, Chryssa; Kanariou, Maria

2014-10-01

197

Frequent transmission of immunodeficiency viruses among bobcats and pumas.  

PubMed

With the exception of human immunodeficiency virus (HIV), which emerged in humans after cross-species transmissions of simian immunodeficiency viruses from nonhuman primates, immunodeficiency viruses of the family Lentiviridae represent species-specific viruses that rarely cross species barriers to infect new hosts. Among the Felidae, numerous immunodeficiency-like lentiviruses have been documented, but only a few cross-species transmissions have been recorded, and these have not been perpetuated in the recipient species. Lentivirus seroprevalence was determined for 79 bobcats (Lynx rufus) and 31 pumas (Puma concolor) from well-defined populations in Southern California. Partial genomic sequences were subsequently obtained from 18 and 12 seropositive bobcats and pumas, respectively. Genotypes were analyzed for phylogenic relatedness and genotypic composition among the study set and archived feline lentivirus sequences. This investigation of feline immunodeficiency virus infection in bobcats and pumas of Southern California provides evidence that cross-species infection has occurred frequently among these animals. The data suggest that transmission has occurred in multiple locations and are most consistent with the spread of the virus from bobcats to pumas. Although the ultimate causes remain unknown, these transmission events may occur as a result of puma predation on bobcats, a situation similar to that which fostered transmission of HIV to humans, and likely represent the emergence of a lentivirus with relaxed barriers to cross-species transmission. This unusual observation provides a valuable opportunity to evaluate the ecological, behavioral, and molecular conditions that favor repeated transmissions and persistence of lentivirus between species. PMID:17670835

Franklin, S P; Troyer, J L; Terwee, J A; Lyren, L M; Boyce, W M; Riley, S P D; Roelke, M E; Crooks, K R; Vandewoude, S

2007-10-01

198

Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection.  

PubMed

Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine ?-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies. PMID:25599590

MacDuff, Donna A; Reese, Tiffany A; Kimmey, Jacqueline M; Weiss, Leslie A; Song, Christina; Zhang, Xin; Kambal, Amal; Duan, Erning; Carrero, Javier A; Boisson, Bertrand; Laplantine, Emmanuel; Israel, Alain; Picard, Capucine; Colonna, Marco; Edelson, Brian T; Sibley, L David; Stallings, Christina L; Casanova, Jean-Laurent; Iwai, Kazuhiro; Virgin, Herbert W

2015-01-01

199

Genetics Home Reference: T-cell immunodeficiency, congenital alopecia, and nail dystrophy  

MedlinePLUS

... Recent literature OMIM Genetic disorder catalog Conditions > T-cell immunodeficiency, congenital alopecia, and nail dystrophy On this ... Glossary definitions Reviewed August 2014 What is T-cell immunodeficiency, congenital alopecia, and nail dystrophy? T-cell ...

200

Absence of cytotoxic antibody to human immunodeficiency virus-infected cells in humans and its induction in animals after infection or immunization with purified envelope glycoprotein gp120  

SciTech Connect

The presence of antibody-dependent complement-mediated cytotoxicity (ACC) was assessed in humans and chimpanzees, which are capable of infection with human immunodeficiency virus isolate HTLV-IIIb, and examined in the goat after immunization with the major viral glycoprotein (gp120) of HTLV-IIIb. In infected humans no antibody mediating ACC was observed regardless of the status of disease. Even healthy individuals with high-titer, broadly reactive, neutralizing antibodies has no ACC. In contrast, chimpanzees infected with HTLV-IIIb, from whom virus could be isolated, not only had neutralizing antibody but also antibodies broadly reactive in ACC, even against distantly related human immunodeficiency virus isolates, as well as against their own reisolated virus. In the goat, the gp120 of HTLV-IIIb induced a highly type-specific response as measured by both ACC and flow cytofluorometry of live infected H9 cells. Normal human cells were not subject to ACC by animal anti-HTLV-III gp120-specific sera. Induction of ACC and neutralizing antibody were closely correlated in the animal experimental models but not in humans. The presence of ACC in gp120-inoculated goats and HTLV-III-infected chimpanzees represent a qualitative difference that may be important in the quest for the elicitation of a protective immunity in humans.

Nara, P.L.; Robey, W.G.; Gonda, M.A.; Carter, S.G.; Fischinger, P.J.

1987-06-01

201

Antifungal prophylaxis during neutropenia and immunodeficiency.  

PubMed Central

Fungal infections represent a major source of morbidity and mortality in patients with almost all types of immunodeficiencies. These infections may be nosocomial (aspergillosis) or community acquired (cryptococcosis), or both (candidiasis). Endemic mycoses such as histoplasmosis, coccidioidomycosis, and penicilliosis may infect many immunocompromised hosts in some geographic areas and thereby create major public health problems. With the wide availability of oral azoles, antifungal prophylactic strategies have been extensively developed. However, only a few well-designed studies involving strict criteria have been performed, mostly in patients with hematological malignancies or AIDS. In these situations, the best dose and duration of administration of the antifungal drug often remain to be determined. In high-risk neutropenic or bone marrow transplant patients, fluconazole is effective for the prevention of superficial and/or systemic candidal infections but is not always able to prolong overall survival and potentially selects less susceptible or resistant Candida spp. Primary prophylaxis against aspergillosis remains investigative. At present, no standard general recommendation for primary antifungal prophylaxis can be proposed for AIDS patients or transplant recipients. However, for persistently immunocompromised patients who previously experienced a noncandidal systemic fungal infection, prolonged suppressive antifungal therapy is often indicated to prevent a relapse. Better strategies for controlling immune deficiencies should also help to avoid some potentially life-threatening deep mycoses. When prescribing antifungal prophylaxis, physicians should be aware of the potential emergence of resistant strains, drug-drug interactions, and the cost. Well-designed, randomized, multicenter clinical trials in high-risk immunocompromised hosts are urgently needed to better define how to prevent severe invasive mycoses. PMID:9227863

Lortholary, O; Dupont, B

1997-01-01

202

Neutralization tests on the SERT 2 spacecraft  

NASA Technical Reports Server (NTRS)

Neutralization test data obtained on the SERT 2 spacecraft are presented. Tests included ion beam neutralization of a thruster by a close (normal design) neutralizer as well as by a distant (1 meter) neutralizer. Parameters affecting neutralization, such as neutralizer bias voltage, neutralizer anode voltage, local spacecraft plasma density, and solar array voltage configuration were varied and changes in plasma potentials were measured. A plasma model is presented as an approximation of observed results.

Kerslake, W. R.; Domitz, S.

1979-01-01

203

Neurosyphilis in a Man with Human Immunodeficiency Virus  

PubMed Central

The authors describe a 33-year-old man with human immunodeficiency virus who developed erythematous macules on the palms and soles with subsequent headaches, papilledema, and iritis. They review the salient characteristics of neurosyphilis with a focus on human immunodeficiency virus-positive individuals. The incidence of syphilis has increased since the year 2000 in African Americans, Hispanics, and men who have sex with men. Treponema pallidum is the causative agent of this disease—a fastidious, slowly growing, microaerophilic spirochete. Sexual contact is the most common mode of transmission. The rapid plasma reagin, Venereal Disease Research Laboratory assay, and fluorescent treponemal antibody absorption assay are commonly used to diagnose syphilis. The mainstay treatment is penicillin. Special considerations exist in the natural history and management of syphilis in the setting of human immunodeficiency virus. PMID:25161759

Sadeghani, Khosro; Kallini, Joseph R.

2014-01-01

204

Expression of envelope glycoproteins of human immunodeficiency virus by an insect virus vector.  

PubMed Central

The envelope gene of human immunodeficiency virus was inserted into the genome of an insect virus vector (Autographa californica nuclear polyhedrosis virus). Upon infection of tissue culture cells, this recombinant virus produced immunoreactive polypeptides related to the envelope glycoproteins of human immunodeficiency virus. Serological survey indicates such polypeptides would be of value as antigens in diagnostics for acquired immunodeficiency syndrome. Images PMID:3312636

Hu, S I; Kosowski, S G; Schaaf, K F

1987-01-01

205

Immunodeficiency-associated Vaccine-Derived Poliovirus Type 3 in Infant, South Africa, 2011  

PubMed Central

Patients with primary immunodeficiency are prone to persistently excrete Sabin-like virus after administration of live-attenuated oral polio vaccine and have an increased risk for vaccine-derived paralytic polio. We report a case of type 3 immunodeficiency-associated vaccine-derived poliovirus in a child in South Africa who was born with X-linked immunodeficiency syndrome. PMID:22607733

Muthambi, Vongani; Schoub, Barry D.

2012-01-01

206

Primary Immunodeficiency in Iran: First Report of the National Registry of PID in Children and Adults  

Microsoft Academic Search

Epidemiological studies have shown wide geographical and racial variation in the prevalence and patterns of immunodeficiency disorders. To determine the frequency of primary immunodeficiencies (PID) in Iran, the Iranian Primary Immunodeficiency Registry (IPIDR) was organized in 1999. We extracted the patient’s data, by using a uniform questionnaire from their hospital records. The diagnosis of patients was based on WHO criteria.

Asghar Aghamohammadi; Mosafa Moein; Abolhasan Farhoudi; Zahra Pourpak; Nima Rezaei; Kamran Abolmaali; Masoud Movahedi; Mohammad Gharagozlou; Bahram Mir Saeid Ghazi; Maryam Mahmoudi; Davoud Mansouri; Saba Arshi; Naser Javaher Trash; Hedayatallah Akbari; Roya Sherkat; Reza Farid Hosayni; Ahmad Hashemzadeh; Iraj Mohammadzadeh; Reza Amin; Sara Kashef; Abdalvahab Alborzi; Abdallah Karimi; Hosaynali Khazaei

2002-01-01

207

Environmental neutralization of polonium-218  

Microsoft Academic Search

Previous work has indicated that two mechanisms of neutralization of the singly charged polonium ion exist. Charged Polonium-218 can be neutralized by reacting with oxygen to form a polonium oxide ion with a higher ionization potential than that of the polonium metal and then accepting an electron transferred from a lower ionization potential gas. In this present work, this mechanism

Scott D. Goldstein; Philip K. Hopke

1985-01-01

208

Neutral theory and community ecology  

Microsoft Academic Search

I review the mathematical and biological aspects of Hubbell's (2001) neutral theory of species abundance for ecological communities, and clarify its historical connections with closely related approaches in population genetics. A selective overview of the empirical evidence for and against this theory is provided, with a special emphasis on tropical plant communities. The neutral theory predicts many of the basic

J. Chave

2004-01-01

209

Preclinical studies in rats and squirrel monkeys for safety evaluation of the bivalent anti-human T cell immunotoxin, A-dmDT390–bisFv(UCHT1)  

Microsoft Academic Search

The bivalent anti-human T cell immunotoxin A-dmDT390-bisFv(UCHT1) for treatment of patients with T cell malignancies is a\\u000a single chain fusion protein composed of the catalytic domain and translocation domains of diphtheria toxin fused to two tandem\\u000a sFv molecules reactive with human CD3?. This immunotoxin selectively kills CD3? positive T cells. To determine the maximum\\u000a tolerated dose (MTD), pharmacokinetics and immunogenicity

Jung Hee Woo; Sarah H. Bour; Tony Dang; Yu-Jen Lee; Seong Kyu Park; Elissa Andreas; Soo Hyun Kang; Jen-Sing Liu; David M. Neville Jr; Arthur E. Frankel

2008-01-01

210

Common variable immunodeficiency disorder - An uncommon cause for bronchiectasis  

PubMed Central

Bronchiectasis continues to be a common respiratory problem of varied etiology. Common variable immunodeficiency disorder (CVID) is an uncommon cause for bronchiectasis. However, the prevalence of bronchiectasis remains very high in patients with CVID. This remains largely an underdiagnosed entity as primary immunodeficiency is not suspected in adults as a cause of bronchiectasis and hence, serum immunoglobulin (Ig) levels are not measured routinely. In addition to bronchiectasis, patients with CVID usually present with various extrapulmonary symptoms. I report here a case of young man who presented with bronchiectasis and multisystem complains who was diagnosed as CVID. PMID:25378851

Panigrahi, Manoj Kumar

2014-01-01

211

Envelope-Modified Single-Cycle Simian Immunodeficiency Virus Selectively Enhances Antibody Responses and Partially Protects against Repeated, Low-Dose Vaginal Challenge ?  

PubMed Central

Immunization of rhesus macaques with strains of simian immunodeficiency virus (SIV) that are limited to a single cycle of infection elicits T-cell responses to multiple viral gene products and antibodies capable of neutralizing lab-adapted SIV, but not neutralization-resistant primary isolates of SIV. In an effort to improve upon the antibody responses, we immunized rhesus macaques with three strains of single-cycle SIV (scSIV) that express envelope glycoproteins modified to lack structural features thought to interfere with the development of neutralizing antibodies. These envelope-modified strains of scSIV lacked either five potential N-linked glycosylation sites in gp120, three potential N-linked glycosylation sites in gp41, or 100 amino acids in the V1V2 region of gp120. Three doses consisting of a mixture of the three envelope-modified strains of scSIV were administered on weeks 0, 6, and 12, followed by two booster inoculations with vesicular stomatitis virus (VSV) G trans-complemented scSIV on weeks 18 and 24. Although this immunization regimen did not elicit antibodies capable of detectably neutralizing SIVmac239 or SIVmac251UCD, neutralizing antibody titers to the envelope-modified strains were selectively enhanced. Virus-specific antibodies and T cells were observed in the vaginal mucosa. After 20 weeks of repeated, low-dose vaginal challenge with SIVmac251UCD, six of eight immunized animals versus six of six naïve controls became infected. Although immunization did not significantly reduce the likelihood of acquiring immunodeficiency virus infection, statistically significant reductions in peak and set point viral loads were observed in the immunized animals relative to the naïve control animals. PMID:20702641

Alpert, Michael D.; Rahmberg, Andrew R.; Neidermyer, William; Ng, Sharon K.; Carville, Angela; Camp, Jeremy V.; Wilson, Robert L.; Piatak, Michael; Mansfield, Keith G.; Li, Wenjun; Miller, Christopher J.; Lifson, Jeffrey D.; Kozlowski, Pamela A.; Evans, David T.

2010-01-01

212

The Selection of Low Envelope Glycoprotein Reactivity to Soluble CD4 and Cold during Simian-Human Immunodeficiency Virus Infection of Rhesus Macaques  

PubMed Central

Envelope glycoprotein (Env) reactivity (ER) describes the propensity of human immunodeficiency virus type 1 (HIV-1) Env to change conformation from the metastable unliganded state in response to the binding of ligands (antibodies and soluble CD4 [sCD4]) or incubation in the cold. To investigate Env properties that favor in vivo persistence, we inoculated rhesus macaques with three closely related CCR5-tropic simian-human immunodeficiency viruses (SHIVs) that differ in ER to cold (ERcold) and ER to sCD4 (ERsCD4); these SHIVs were neutralized by antibodies equivalently and thus were similar in ERantibody. All three SHIVs achieved high levels of acute viremia in the monkeys without alteration of their Env sequences, indicating that neither ERcold nor ERsCD4 significantly influences the establishment of infection. Between 14 and 100 days following infection, viruses with high ERcold and ERsCD4 were counterselected. Remarkably, the virus variant with low ERcold and low ERsCD4 did not elicit a neutralizing antibody response against the infecting virus, despite the generation of high levels of anti-Env antibodies in the infected monkeys. All viruses that achieved persistent viremia escaped from any autologous neutralizing antibodies and exhibited low ERcold and low ERsCD4. One set of gp120 changes determined the decrease in ERcold and ERsCD4, and a different set of gp120 changes determined resistance to autologous neutralizing antibodies. Each set of changes contributed to a reduction in Env-mediated entry. During infection of monkeys, any Env replication fitness costs associated with decreases in ERcold and ERsCD4 may be offset by minimizing the elicitation of autologous neutralizing antibodies. PMID:24131720

McGee, Kathleen; Haim, Hillel; Korioth-Schmitz, Birgit; Espy, Nicole; Javanbakht, Hassan; Letvin, Norman

2014-01-01

213

Science and ethics of human immunodeficiency virus/acquired immunodeficiency syndrome controversies in Africa.  

PubMed

The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic in Africa has raised important ethical issues for both researchers and clinicians. The most notorious controversy has been related to the zidovudine (AZT) trials in Africa in the late 1990s, in which the control groups were given a placebo rather than an effective drug to prevent vertical transmission. This raised concerns in the sponsoring country about exploitation of subjects, injustice and an ethical double standard between donor countries and resource-poor settings. However, the real double standard is between clinical practice standards in Western versus African countries, which must be addressed as part of the increasing global inequity of wealth both between countries and also within countries. There are important limitations to ethical declarations, principles and guidelines on their own without contextual ethical reasoning. The focus on research ethics with the HIV epidemic has led to a relative neglect of ethical issues in clinical practice. Although the scientific advances in HIV/AIDS have changed the ethical issues since the 1990s, there has also been progress in the bioethics of HIV/AIDS in terms of ethical review capability by local committees as well as in exposure to ethical issues by clinicians and researchers in Africa. However, serious concerns remain about the overregulation of research by bureaucratic agencies which could discourage African research on specifically African health issues. There is also a need for African academic institutions and researchers to progressively improve their research capacity with the assistance of research funders and donor agencies. PMID:21951451

Brewster, David

2011-09-01

214

Distinct Evolutionary Pressures Underlie Diversity in Simian Immunodeficiency Virus and Human Immunodeficiency Virus Lineages  

PubMed Central

Simian immunodeficiency virus (SIV) infection of rhesus macaques causes immune depletion and disease closely resembling human AIDS and is well recognized as the most relevant animal model for the human disease. Experimental investigations of viral pathogenesis and vaccine protection primarily involve a limited set of related viruses originating in sooty mangabeys (SIVsmm). The diversity of human immunodeficiency virus type 1 (HIV-1) has evolved in humans in about a century; in contrast, SIV isolates used in the macaque model evolved in sooty mangabeys over millennia. To investigate the possible consequences of such different evolutionary histories for selection pressures and observed diversity in SIVsmm and HIV-1, we isolated, sequenced, and analyzed 20 independent isolates of SIVsmm, including representatives of 7 distinct clades of viruses isolated from natural infection. We found SIVsmm diversity to be lower overall than HIV-1 M group diversity. Reduced positive selection (i.e., less diversifying evolution) was evident in extended regions of SIVsmm proteins, most notably in Gag p27 and Env gp120. In addition, the relative diversities of proteins in the two lineages were distinct: SIVsmm Env and Gag were much less diverse than their HIV-1 counterparts. This may be explained by lower SIV-directed immune activity in mangabeys relative to HIV-1-directed immunity in humans. These findings add an additional layer of complexity to the interpretation and, potentially, to the predictive utility of the SIV/macaque model, and they highlight the unique features of human and simian lentiviral evolution that inform studies of pathogenesis and strategies for AIDS vaccine design. PMID:23055550

Apetrei, Cristian; Santiago, Mario L.; Li, Yingying; Gautam, Rajeev; Pandrea, Ivona; Shaw, George M.; Hahn, Beatrice H.; Letvin, Norman L.; Nabel, Gary J.

2012-01-01

215

Environmental neutralization of polonium-218  

SciTech Connect

Previous work has indicated that two mechanisms of neutralization of the singly charged polonium ion exist. Charged Polonium-218 can be neutralized by reacting with oxygen to form a polonium oxide ion with a higher ionization potential than that of the polonium metal and then accepting an electron transferred from a lower ionization potential gas. In this present work, this mechanism has been verified by determining that the polonium oxide has an ionization potential in the range 10.35-10.53 eV. It was also previously reported that /sup 218/Po can be neutralized, in the absence of oxygen, by the scavenging of electrons by a trace gas such as water or nitrogen dioxide and their diffusion to the polonium ion. To verify this second neutralization mechanism, concentrations of nitrogen dioxide in nitrogen in the range of 50 ppb-1 ppm were examined for their ability to neutralize the polonium ion. Complete neutralization of /sup 218/Po was observed at nitrogen dioxide concentrations greater than 700 ppb. For concentrations below 700 ppb, the degree of neutralization was found to increase smoothly with the nitrogen dioxide concentration.

Goldstein, S.D.; Hopke, P.K.

1985-01-01

216

Differences in the antibody response to human immunodeficiency virus-1 envelope glycoprotein (gp160) in infected laboratory workers and vaccinees.  

PubMed Central

Studies of the immune response to the human immunodeficiency virus (HIV) have been hampered by the antigenic diversity of the HIV envelope protein. In an effort to predict the efficacy of vaccination we have compared the systemic anti-envelope antibody response in seronegative volunteers immunized with recombinant gp160 (either in vaccinia or as soluble protein produced in baculovirus) derived from the HTLV-IIIB strain of HIV-1 and in two laboratory workers accidentally infected with the same strain. 11 of 14 vaccinees responded to immunization by producing anti-gp160 of similar titer and the same isotype as that seen in the laboratory workers. Four vaccinees also had antibody to the principal neutralizing domain (V3 loop) that was comparable in titer with that seen in the laboratory workers, but the fine specificity of anti-V3 antibody was qualitatively different in the two groups. Antibody that can block the interaction between CD4 and gp120 was present at comparable levels in three vaccines and the lab workers. Neutralizing antibody titers were markedly lower in the vaccinees than in the laboratory workers. In seven of the vaccinees, an immunodominant epitope was at amino acid 720-740. Analyses of monoclonal antibodies to this region indicate that they do not neutralize, bind to infected cells, nor function as immunotoxins. Although the anti-gp160 antibody response was of similar magnitude in both infected and vaccinated individuals, there were important qualitative differences. PMID:7683694

Pincus, S H; Messer, K G; Schwartz, D H; Lewis, G K; Graham, B S; Blattner, W A; Fisher, G

1993-01-01

217

Gene-Based Vaccination with a Mismatched Envelope Protects against Simian Immunodeficiency Virus Infection in Nonhuman Primates  

PubMed Central

The RV144 trial demonstrated that an experimental AIDS vaccine can prevent human immunodeficiency virus type 1 (HIV-1) infection in humans. Because of its limited efficacy, further understanding of the mechanisms of preventive AIDS vaccines remains a priority, and nonhuman primate (NHP) models of lentiviral infection provide an opportunity to define immunogens, vectors, and correlates of immunity. In this study, we show that prime-boost vaccination with a mismatched SIV envelope (Env) gene, derived from simian immunodeficiency virus SIVmac239, prevents infection by SIVsmE660 intrarectally. Analysis of different gene-based prime-boost immunization regimens revealed that recombinant adenovirus type 5 (rAd5) prime followed by replication-defective lymphocytic choriomeningitis virus (rLCMV) boost elicited robust CD4 and CD8 T-cell and humoral immune responses. This vaccine protected against infection after repetitive mucosal challenge with efficacies of 82% per exposure and 62% cumulatively. No effect was seen on viremia in infected vaccinated monkeys compared to controls. Protection correlated with the presence of neutralizing antibodies to the challenge viruses tested in peripheral blood mononuclear cells. These data indicate that a vaccine expressing a mismatched Env gene alone can prevent SIV infection in NHPs and identifies an immune correlate that may guide immunogen selection and immune monitoring for clinical efficacy trials. PMID:22593152

Flatz, Lukas; Cheng, Cheng; Wang, Lingshu; Foulds, Kathryn E.; Ko, Sung-Youl; Kong, Wing-Pui; Roychoudhuri, Rahul; Shi, Wei; Bao, Saran; Todd, John-Paul; Asmal, Mohammed; Shen, Ling; Donaldson, Mitzi; Schmidt, Stephen D.; Gall, Jason G. D.; Pinschewer, Daniel D.; Letvin, Norman L.; Rao, Srinivas; Mascola, John R.; Roederer, Mario

2012-01-01

218

Macaque Long-Term Nonprogressors Resist Superinfection with Multiple CD8+ T Cell Escape Variants of Simian Immunodeficiency Virus?  

PubMed Central

Human immunodeficiency virus (HIV)-positive individuals can be superinfected with different virus strains. Individuals who control an initial HIV infection are therefore still at risk for subsequent infection with divergent viruses, but the barriers to such superinfection remain unclear. Here we tested long-term nonprogressors' (LTNPs') susceptibility to superinfection using Indian rhesus macaques that express the major histocompatibility complex class I (MHC-I) allele Mamu-B*17, which is associated with control of the pathogenic AIDS virus SIVmac239. The Mamu-B*17-restricted CD8+ T cell repertoire is focused almost entirely on 5 epitopes. We engineered a series of SIVmac239 variants bearing mutations in 3, 4, or all 5 of these epitopes and used them to serially challenge 2 Mamu-B*17-positive LTNPs. None of the escape variants caused breakthrough replication in LTNPs, although they readily infected Mamu-B*17-negative naive macaques. In vitro competing coculture assays and examination of viral evolution in hosts lacking Mamu-B*17 suggested that the mutant viruses had negligible defects in replicative fitness. Both LTNPs maintained robust immune responses, including simian immunodeficiency virus (SIV)-specific CD8+ and CD4+ T cells and neutralizing antibodies. Our results suggest that escape mutations in epitopes bound by “protective” MHC-I molecules may not be sufficient to establish superinfection in LTNPs. PMID:20962091

Weinfurter, Jason T.; May, Gemma E.; Soma, Taeko; Hessell, Ann J.; León, Enrique J.; MacNair, Caitlin E.; Piaskowski, Shari M.; Weisgrau, Kim; Furlott, Jessica; Maness, Nicholas J.; Reed, Jason; Wilson, Nancy A.; Rakasz, Eva G.; Burton, Dennis R.; Friedrich, Thomas C.

2011-01-01

219

The Antiparticles of Neutral Bosons  

E-print Network

With the advent of the ability to create and study antihydrogen, we think it is appropriate to consider the possibility that antiphotons might not be identical to photons. First of all, we will look at the experimental evidence concerning multiple neutral pions and multiple photons. Because of its internal structure, the neutral kaon is not identical to its antiparticle. We will consider internal structures for the neutral pion and photon for which the antiparticle differs from the particle. Interestingly, the antiphoton thus created from neutrinos does not interact with electrons because its neutrinos have the wrong helicity.

Perkins, Walton A

2013-01-01

220

The Antiparticles of Neutral Bosons  

E-print Network

With the advent of the ability to create and study antihydrogen, we think it is appropriate to consider the possibility that antiphotons might not be identical to photons. First of all, we will look at the experimental evidence concerning multiple neutral pions and multiple photons. Because of its internal structure, the neutral kaon is not identical to its antiparticle. We will consider internal structures for the neutral pion and photon for which the antiparticle differs from the particle. Interestingly, the antiphoton thus created from neutrinos does not interact with electrons because its neutrinos have the wrong helicity.

Walton A. Perkins

2013-11-15

221

Sequential injection immunoassay for human bone morphogenic protein-7 using an immunoreactor immobilized with anti-human bone morphogenic protein-7 antibody--CdSe/ZnS quantum dot conjugates.  

PubMed

The detection of human bone morphogenic protein-7 (BMP-7) was achieved using a sequential injection immunoassay (SIIA) system. The SIIA system is based on the binding between BMP-7 and anti-human BMP-7 (AbBMP7)-CdSe/ZnS quantum dot (QD) conjugates immobilized onto a glass disk or an optical fiber, using fluorescence detection at excitation and emission wavelengths of 470 nm and 580 nm, respectively. The AbBMP7-QD conjugates were prepared by conjugating anti-human BMP-7 antibody (AbBMP7) to hydrophilic CdSe/ZnS core/shell quantum dots (QDs). The SIIA system was fully automated using software written in the LabVIEW™ development environment. The analytical performance of the SIIA system was characterized with a number of variables such as carrier flow rate and elution buffer. Under partially optimized operating conditions, the SIIA system had a linear calibration graph at up to 10.0 ng mL(-1) BMP-7 (R(2)?0.975) and a sample frequency of two samples per hour. The SIIA system with an optical fiber immunosensor was used to detect and quantify BMP-7 in spiked real samples obtained from a biological process with recoveries in the range of 95-102%. PMID:23790295

Kim, Chun-Kwang; Duong, Hong Dinh; Rhee, Jong Il

2013-07-01

222

Reversion of CTL escape–variant immunodeficiency viruses in vivo  

Microsoft Academic Search

Engendering cytotoxic T-lymphocyte (CTL) responses is likely to be an important goal of HIV vaccines. However, CTLs select for viral variants that escape immune detection. Maintenance of such escape variants in human populations could pose an obstacle to HIV vaccine development. We first observed that escape mutations in a heterogeneous simian immunodeficiency virus (SIV) isolate were lost upon passage to

Thomas C Friedrich; Elizabeth J Dodds; Levi J Yant; Lara Vojnov; Richard Rudersdorf; Candice Cullen; David T Evans; Ronald C Desrosiers; Bianca R Mothé; John Sidney; Alessandro Sette; Kevin Kunstman; Steven Wolinsky; Michael Piatak; Jeffrey Lifson; Austin L Hughes; Nancy Wilson; David H O'Connor; David I Watkins

2004-01-01

223

The Presidential Commission on the Human Immunodeficiency Virus Epidemic Report.  

ERIC Educational Resources Information Center

This document presents findings of the Presidential Commission on the Human Immunodeficiency Virus (HIV) epidemic. The executive summary lists 20 major findings and recommendations which together comprise a comprehensive national strategy for managing the HIV epidemic. The commission recommends: (1) replacement of the obsolete term "AIDS"…

Presidential Commission on the Human Immunodeficiency Virus Epidemic, Washington, DC.

224

Spatial Analysis of Feline Immunodeficiency Virus Infection in Cougars  

PubMed Central

The cougar (Puma concolor) is a large predatory feline found widely in the Americas that is susceptible to feline immunodeficiency virus (FIV), a fast-evolving lentivirus found in wild feline species that is analogous to simian immunodeficiency viruses in wild primates and belongs to the same family of viruses as human immunodeficiency virus. FIV infection in cougars can lead to a weakened immune system that creates opportunities for other infecting agents. FIV prevalence and lineages have been studied previously in several areas in the western United States, but typically without spatially explicit statistical techniques. To describe the distribution of FIV in a sample of cougars located in the northern Rocky Mountain region of North America, we first used kernel density ratio estimation to map the log relative risk of FIV. The risk surface showed a significant cluster of FIV in northwestern Montana. We also used Bayesian cluster models for genetic data to investigate the spatial structure of the feline immunodeficiency virus with virus genetic sequence data. A result of the models was two spatially distinct FIV lineages that aligned considerably with an interstate highway in Montana. Our results suggest that the use of spatial information and models adds novel insight when investigating an infectious animal disease. The results also suggest that the influence of landscape features likely plays an important role in the spatiotemporal spread of an infectious disease within wildlife populations. PMID:21197421

Wheeler, David C.; Waller, Lance A.; Biek, Roman

2010-01-01

225

Spatial analysis of feline immunodeficiency virus infection in cougars.  

PubMed

The cougar (Puma concolor) is a large predatory feline found widely in the Americas that is susceptible to feline immunodeficiency virus (FIV), a fast-evolving lentivirus found in wild feline species that is analogous to simian immunodeficiency viruses in wild primates and belongs to the same family of viruses as human immunodeficiency virus. FIV infection in cougars can lead to a weakened immune system that creates opportunities for other infecting agents. FIV prevalence and lineages have been studied previously in several areas in the western United States, but typically without spatially explicit statistical techniques. To describe the distribution of FIV in a sample of cougars located in the northern Rocky Mountain region of North America, we first used kernel density ratio estimation to map the log relative risk of FIV. The risk surface showed a significant cluster of FIV in northwestern Montana. We also used Bayesian cluster models for genetic data to investigate the spatial structure of the feline immunodeficiency virus with virus genetic sequence data. A result of the models was two spatially distinct FIV lineages that aligned considerably with an interstate highway in Montana. Our results suggest that the use of spatial information and models adds novel insight when investigating an infectious animal disease. The results also suggest that the influence of landscape features likely plays an important role in the spatiotemporal spread of an infectious disease within wildlife populations. PMID:21197421

Wheeler, David C; Waller, Lance A; Biek, Roman

2010-07-01

226

Fraunhofer lines in the solar spectrum and immunodeficiency problems  

NASA Astrophysics Data System (ADS)

The importance of the presence of Fraunhofer lines in the solar spectrum for development of immunodeficiency has been demonstrated. In vitro and in vivo tests of illumination within Mg lines have proved the possibility to reduce the level of HIV/AIDS development.

Kondratyev, K. Ya.; Fedchenko, P. P.

2004-05-01

227

Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice  

PubMed Central

Infantile hemangioma is a benign endothelial tumor composed of disorganized blood vessels. It exhibits a unique life cycle of rapid postnatal growth followed by slow regression to a fibrofatty residuum. Here, we have reported the isolation of multipotential stem cells from hemangioma tissue that give rise to hemangioma-like lesions in immunodeficient mice. Cells were isolated based on expression of the stem cell marker CD133 and expanded from single cells as clonal populations. The CD133-selected cells generated human blood vessels 7 days after implantation in immunodeficient mice. Cell retrieval experiments showed the cells could again form vessels when transplanted into secondary recipients. The human vessels expressed GLUT-1 and merosin, immunodiagnostic markers for infantile hemangioma. Two months after implantation, the number of blood vessels diminished and human adipocytes became evident. Lentiviral expression of GFP was used to confirm that the hemangioma-derived cells formed the blood vessels and adipocytes in the immunodeficient mice. Thus, when transplanted into immunodeficient mice, hemangioma-derived cells recapitulated the unique evolution of infantile hemangioma — the formation of blood vessels followed by involution to fatty tissue. In summary, this study identifies a stem cell as the cellular origin of infantile hemangioma and describes for what we believe is the first time an animal model for this common tumor of infancy. PMID:18535669

Khan, Zia A.; Boscolo, Elisa; Picard, Arnaud; Psutka, Sarah; Melero-Martin, Juan M.; Bartch, Tatianna C.; Mulliken, John B.; Bischoff, Joyce

2008-01-01

228

Immunopathology and Infectious Diseases Simian Immunodeficiency Virus Infection Alters  

E-print Network

.2010.091288) Pulmonary diseases are frequent complications of HIV-1 infection, affecting 75% to 85Immunopathology and Infectious Diseases Simian Immunodeficiency Virus Infection Alters Chemokine. Kirschner,§ and Todd A. Reinhart* From the Department of Infectious Diseases and Microbiology,* Graduate

Kirschner, Denise

229

Demodicosis in two cats seropositive for feline immunodeficiency virus.  

PubMed

Two cats were diagnosed with generalized demodicosis. Serotest results were negative for FeLV and positive for feline immunodeficiency virus. In one cat, demodicosis resolved in response to topical application of lime-sulfur solution, but the other cat was euthanatized. PMID:2537276

Chalmers, S; Schick, R O; Jeffers, J

1989-01-15

230

Behçet's disease in a patient with immunodeficiency virus infection  

Microsoft Academic Search

A patient with human immunodeficiency virus (HIV) infection who developed Behçet's disease is described. As various vasculitis syndromes have been encountered recently in association with HIV infection it is suggested that Behçet's disease may be related to the HIV infection in this patient.

D Buskila; D D Gladman; J Gilmore; I E Salit

1991-01-01

231

The Human Immunodeficiency Virus: Infectivity and Mechanisms of Pathogenesis.  

ERIC Educational Resources Information Center

Discusses how the infection of the human immunodeficiency virus (HIV) results in a profound immunosuppression due predominantly to a selective depletion of helper/inducer T lymphocytes that express the receptor for the virus, as well as neuropsychiatric abnormalities in the brain. (TW)

Fauci, Anthony S.

1988-01-01

232

Severe tuberculosis in patients with human immunodeficiency virus infection  

Microsoft Academic Search

Tuberculosis has now been well documented as a complication of infection with human immunodeficiency virus (HIV), but no studies concern patients requiring admission to the ICU. We report 12 cases of severe disseminated tuberculosis in patients who were seropositive for HIV. Eight patients had diffuse pulmonary involvement responsible for acute respiratory failure, 7 of whom required mechanical ventilation. Four developed

B. Gachot; M. Wolff; B. Clair; B. Régnier

1990-01-01

233

6 CFR 27.305 - Neutral adjudications.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 2010-01-01 false Neutral adjudications. 27.305 Section 27...Orders and Adjudications § 27.305 Neutral adjudications. (a) Any facility...300 is entitled to an adjudication, by a neutral adjudications officer, of any...

2010-01-01

234

Frequent transmission of immunodeficiency viruses among bobcats and pumas  

USGS Publications Warehouse

With the exception of human immunodeficiency virus (HIV), which emerged in humans after cross-species transmissions of simian immunodeficiency viruses from nonhuman primates, immunodeficiency viruses of the family Lentiviridae represent species-specific viruses that rarely cross species barriers to infect new hosts. Among the Felidae, numerous immunodeficiency-like lentiviruses have been documented, but only a few cross-species transmissions have been recorded, and these have not been perpetuated in the recipient species. Lentivirus seroprevalence was determined for 79 bobcats (Lynx rufus) and 31 pumas (Puma concolor) from well-defined populations in Southern California. Partial genomic sequences were subsequently obtained from 18 and 12 seropositive bobcats and pumas, respectively. Genotypes were analyzed for phylogenic relatedness and genotypic composition among the study set and archived feline lentivirus sequences. This investigation of feline immunodeficiency virus infection in bobcats and pumas of Southern California provides evidence that cross-species infection has occurred frequently among these animals. The data suggest that transmission has occurred in multiple locations and are most consistent with the spread of the virus from bobcats to pumas. Although the ultimate causes remain unknown, these transmission events may occur as a result of puma predation on bobcats, a situation similar to that which fostered transmission of HIV to humans, and likely represent the emergence of a lentivirus with relaxed barriers to cross-species transmission. This unusual observation provides a valuable opportunity to evaluate the ecological, behavioral, and molecular conditions that favor repeated transmissions and persistence of lentivirus between species. Copyright ?? 2007, American Society for Microbiology. All Rights Reserved.

Franklin, S.P.; Troyer, J.L.; TerWee, J.A.; Lyren, L.M.; Boyce, W.M.; Riley, S.P.D.; Roelke, M.E.; Crooks, K.R.; VandeWoude, S.

2007-01-01

235

Improbability of effective vaccination against human immunodeficiency virus because of its intracellular transmission and rectal portal of entry.  

PubMed Central

The worldwide effort to produce a vaccine against AIDS continues to disregard the fact that even human immunodeficiency virus (HIV)-specific neutralizing antibodies and cell-mediated immunity are ineffective against virus within cells without viral antigens on the cell membrane--and that much of HIV infection is transmitted in this manner. According to a recent report, a simian immunodeficiency virus vaccine that protected monkeys against an intravenous challenge with cell-free virus was, as predicted, ineffective against an intravenous challenge with the same amount of virus in infected cells. Moreover, antibody and HIV have been found to coexist in cell-free plasma from asymptomatic and symptomatic patients. Excluding direct introduction of HIV into the blood-stream, the most common and efficient form of transmission of HIV infection is by receptive anal intercourse, and semen contains large numbers of infected cells per milliliter. Recent reports showing that colorectal cells can be persistently infected by HIV and that HIV RNA and cDNA are present in the cells of the colon of dead AIDS patients indicate that either cell-free or intracellular HIV has the capacity to multiply at the portal of entry in the colorectal area without interference from neutralizing antibodies. The available data provide no basis for testing any HIV vaccine in human beings either before or after infection. The main challenge is to find a way to kill cells with chromosomally integrated HIV cDNA without harming normal cells, perhaps by identifying repressor proteins that might be produced by the cells with integrated HIV cDNA and thus could become specific targets for cell-killing drugs. PMID:1528902

Sabin, A B

1992-01-01

236

Vendor neutral archive in PACS.  

PubMed

An archive is a location containing a collection of records, documents, or other materials of historical importance. An integral part of Picture Archiving and Communication System (PACS) is archiving. When a hospital needs to migrate a PACS vendor, the complete earlier data need to be migrated in the format of the newly procured PACS. It is both time and money consuming. To address this issue, the new concept of vendor neutral archive (VNA) has emerged. A VNA simply decouples the PACS and workstations at the archival layer. This is achieved by developing an application engine that receives, integrates, and transmits the data using the different syntax of a Digital Imaging and Communication in Medicine (DICOM) format. Transferring the data belonging to the old PACS to a new one is performed by a process called migration of data. In VNA, a number of different data migration techniques are available to facilitate transfer from the old PACS to the new one, the choice depending on the speed of migration and the importance of data. The techniques include simple DICOM migration, prefetch-based DICOM migration, medium migration, and the expensive non-DICOM migration. "Vendor neutral" may not be a suitable term, and "architecture neutral," "PACS neutral," "content neutral," or "third-party neutral" are probably better and preferred terms. Notwithstanding this, the VNA acronym has come to stay in both the medical IT user terminology and in vendor nomenclature, and radiologists need to be aware of its impact in PACS across the globe. PMID:23833411

Agarwal, Tapesh Kumar; Sanjeev

2012-10-01

237

Robust neutralizing antibodies elicited by HIV-1 JRFL envelope glycoprotein trimers in nonhuman primates.  

PubMed

Host cell-mediated proteolytic cleavage of the human immunodeficiency virus type 1 (HIV-1) gp160 precursor glycoprotein into gp120 and gp41 subunits is required to generate fusion-competent envelope glycoprotein (Env) spikes. The gp120-directed broadly neutralizing monoclonal antibodies (bNabs) isolated from HIV-infected individuals efficiently recognize fully cleaved JRFL Env spikes; however, nonneutralizing gp120-directed monoclonal antibodies isolated from infected or vaccinated subjects recognize only uncleaved JRFL spikes. Therefore, as an immunogen, cleaved spikes that selectively present desired neutralizing epitopes to B cells may elicit cross-reactive neutralizing antibodies. Accordingly, we inoculated nonhuman primates (NHPs) with plasmid DNA encoding transmembrane-anchored, cleaved JRFL Env or by electroporation (EP). Priming with DNA expressing soluble, uncleaved gp140 trimers was included as a comparative experimental group of NHPs. DNA inoculation was followed by boosts with soluble JRFL gp140 trimers, and control NHPs were inoculated with soluble JRFL protein trimers without DNA priming. In the TZM-bl assay, elicitation of neutralizing antibodies against HIV-1 tier 1 isolates was robust following the protein boost. Neutralization of tier 2 isolates was detected, but only in animals primed with plasmid DNA and boosted with trimeric protein. Using the more sensitive A3R5 assay, consistent neutralization of both clade B and C tier 2 isolates was detected from all regimens assessed in the current study, exceeding levels achieved by our previous vaccine regimens in primates. Together, these data suggest a potential advantage of B cell priming followed by a rest interval and protein boosting to present JRFL Env spikes to the immune system to better generate HIV-1 cross-clade neutralizing antibodies. PMID:24067980

Chakrabarti, Bimal K; Feng, Yu; Sharma, Shailendra Kumar; McKee, Krisha; Karlsson Hedestam, Gunilla B; Labranche, Celia C; Montefiori, David C; Mascola, John R; Wyatt, Richard T

2013-12-01

238

Robust Neutralizing Antibodies Elicited by HIV-1 JRFL Envelope Glycoprotein Trimers in Nonhuman Primates  

PubMed Central

Host cell-mediated proteolytic cleavage of the human immunodeficiency virus type 1 (HIV-1) gp160 precursor glycoprotein into gp120 and gp41 subunits is required to generate fusion-competent envelope glycoprotein (Env) spikes. The gp120-directed broadly neutralizing monoclonal antibodies (bNabs) isolated from HIV-infected individuals efficiently recognize fully cleaved JRFL Env spikes; however, nonneutralizing gp120-directed monoclonal antibodies isolated from infected or vaccinated subjects recognize only uncleaved JRFL spikes. Therefore, as an immunogen, cleaved spikes that selectively present desired neutralizing epitopes to B cells may elicit cross-reactive neutralizing antibodies. Accordingly, we inoculated nonhuman primates (NHPs) with plasmid DNA encoding transmembrane-anchored, cleaved JRFL Env or by electroporation (EP). Priming with DNA expressing soluble, uncleaved gp140 trimers was included as a comparative experimental group of NHPs. DNA inoculation was followed by boosts with soluble JRFL gp140 trimers, and control NHPs were inoculated with soluble JRFL protein trimers without DNA priming. In the TZM-bl assay, elicitation of neutralizing antibodies against HIV-1 tier 1 isolates was robust following the protein boost. Neutralization of tier 2 isolates was detected, but only in animals primed with plasmid DNA and boosted with trimeric protein. Using the more sensitive A3R5 assay, consistent neutralization of both clade B and C tier 2 isolates was detected from all regimens assessed in the current study, exceeding levels achieved by our previous vaccine regimens in primates. Together, these data suggest a potential advantage of B cell priming followed by a rest interval and protein boosting to present JRFL Env spikes to the immune system to better generate HIV-1 cross-clade neutralizing antibodies. PMID:24067980

Feng, Yu; Sharma, Shailendra Kumar; McKee, Krisha; Karlsson Hedestam, Gunilla B.; LaBranche, Celia C.; Montefiori, David C.; Mascola, John R.

2013-01-01

239

Systemic lymphadenopathic histology in human immunodeficiency virus-1-seropositive drug addicts without apparent acquired immunodeficiency syndrome.  

PubMed

We examined lymph nodes from multiple sites in 50 individuals infected with human immunodeficiency virus (HIV-1) who died accidentally of drug overdoses and in whom there was no evidence of opportunistic infection. The size, histologic pattern, presence of Warthin-Finkeldey-type giant cells, and estimation of CD4 cell count of these lymph nodes were compared with those of 13 seronegative drug addicts (controls). Lymph nodes from seropositive individuals were slightly but significantly larger than those of controls. Lymph nodes from seropositive cases were much more likely to contain secondary follicles (90%) than were those from controls (20%). Unlike follicles in control nodes, most secondary follicles in the seropositive cases were in various stages of fragmentation and involution. As follicular changes progressed, there was a decrease in CD4 cells and an increase in intrafollicular and paracortical plasma cells. Plasmacytosis was much more prevalent in lymph nodes from seropositive individuals than in controls. Warthin-Finkeldey-type giant cells were present in at least one node in 29 of 50 seropositive cases, were most numerous in those showing follicular hyperplasia with fragmentation (45% of cases), and were especially numerous in Peyer's patches (61% of cases). There was generally good concordance of HIV-1-associated follicular morphology among diverse lymph node groups. There is prolonged generalized, mild hyperplastic lymphadenopathy with frequent syncytial cells in intravenous drug addicts with asymptomatic HIV-1 infection. PMID:8150456

Burke, A P; Anderson, D; Mannan, P; Ribas, J L; Liang, Y H; Smialek, J; Virmani, R

1994-03-01

240

Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals  

SciTech Connect

Eight rhesus macaques were immunized four times over a period of 8 months with a psoralen-UV-light-inactivated whole simian immunodeficiency virus vaccine adjuvanted with threonyl muramyl dipeptide. Eight unvaccinated control animals received adjuvant alone. Only the vaccinated animals made antibodies before challenge exposure to the viral core and envelope as determined by Western blotting (immunoblotting) and virus-neutralizing antibodies. Ten days after the final immunization, one-half of the vaccinated and nonvaccinated monkeys were challenged exposed intravenously (i.v.) and one-half were challenge exposed via the genital mucosa with virulent simian immunodeficiency virus. All of the nonvaccinated control monkeys became persistently infected. In spite of preexisting neutralizing antibodies and an anamnestic antibody response, all of the immunized monkeys also became persistently infected. However, there was evidence that the clinical course in immunized i.v. infected animals was delayed. All four mock-vaccinated i.v. challenge-exposed animals died with disease from 3 to 9 months postchallenge. In contrast, only one of four vaccinated i.v. challenge-exposed monkeys had died by 11 months postchallenge.

Sutjipto, S.; Pedersen, N.C.; Miller, C.J.; Gardner, M.B.; Hanson, C.V.; Gettie, A.; Jennings, M.; Higgins, J.; Marx, P.A. (Univ. of California, Davis (USA))

1990-05-01

241

In Vitro Characterization of a Simian Immunodeficiency Virus-Human Immunodeficiency Virus (HIV) Chimera Expressing HIV Type 1 Reverse Transcriptase To Study Antiviral Resistance in Pigtail Macaques  

Microsoft Academic Search

Antiviral resistance is a significant obstacle in the treatment of human immunodeficiency virus type 1 (HIV-1)- infected individuals. Because nonnucleoside reverse transcriptase inhibitors (NNRTIs) specifically target HIV-1 reverse transcriptase (RT) and do not effectively inhibit simian immunodeficiency virus (SIV) RT, the development of animal models to study the evolution of antiviral resistance has been problematic. To facilitate in vivo studies

Zandrea Ambrose; Valerie Boltz; Sarah Palmer; John M. Coffin; Stephen H. Hughes; Vineet N. KewalRamani

2004-01-01

242

Acquired immunodeficiency syndrome associated with blood-product transfusions  

SciTech Connect

A 53-year-old white man had fever, malaise, and dyspnea on exertion. His chest roentgenogram was normal, but pulmonary function tests showed impaired diffusion capacity and a gallium scan showed marked uptake in the lungs. Results of an open-lung biopsy documented Pneumocystis carinii pneumonia. Immunologic test results were consistent with the acquired immunodeficiency syndrome. The patient denied having homosexual contact or using intravenous drugs. Twenty-nine months before the diagnosis of pneumocystis pneumonia was made, the patient had had 16 transfusions of whole blood, platelets, and fresh-frozen plasma during coronary artery bypass surgery at another medical center. This patient is not a member of any currently recognized high-risk group and is believed to have contracted the acquired immunodeficiency syndrome from blood and blood-product transfusions.

Jett, J.R.; Kuritsky, J.N.; Katzmann, J.A.; Homburger, H.A.

1983-11-01

243

Thirty years of the human immunodeficiency virus epidemic and beyond  

PubMed Central

After more than 30 years of battling a global epidemic, the prospect of eliminating human immunodeficiency virus (HIV) as the most challenging infectious disease of the modern era is within our reach. Major scientific discoveries about the virus responsible for this immunodeficiency disease state, including its pathogenesis, transmission patterns and clinical course, have led to the development of potent antiretroviral drugs that offer great hopes in HIV treatment and prevention. Although these agents and many others still in development and testing are capable of effectively suppressing viral replication and survival, the medical management of HIV infection at the individual and the population levels remains challenging. Timely initiation of antiretroviral drugs, adherence to the appropriate therapeutic regimens, effective use of these agents in the pre and post-exposure prophylaxis contexts, treatment of comorbid conditions and addressing social and psychological factors involved in the care of individuals continue to be important considerations. PMID:24136672

Younai, Fariba S

2013-01-01

244

Transactivation of human immunodeficiency virus promoter by human herpesvirus 6.  

PubMed Central

Patients with acquired immunodeficiency syndrome (AIDS) are often infected with a number of other heterologous viruses in addition to the initial human immunodeficiency virus (HIV) infection, and these agents could act as potential reactivating agents of latent HIV. A new antigenically distinct herpesvirus, designated human herpesvirus 6 (HHV-6), has recently been isolated from patients with AIDS and has been shown to infect a number of different human cells, specifically human T cells, B cells, and glial cells. Since these are some of the same cells that harbor the AIDS virus, it is quite important to determine any interaction between this new herpesvirus and HIV. In this report, we demonstrate that HHV-6 can trans-activate the HIV promoter in human T-cell lines as measured by the expression of the bacterial gene chloramphenicol acetyltransferase. This indicates that stimulation of HIV gene expression by HHV-6 could play a role in HIV pathogenesis. Images PMID:2911127

Horvat, R T; Wood, C; Balachandran, N

1989-01-01

245

Romiplostim as early treatment of immune thrombocytopenia with severe immunodeficiency  

PubMed Central

Immunosuppressive agents are the standard therapeutic approach for immune thrombocy-topenia (ITP). Their prolonged use may increase the risk of infectious complications, particularly when the patient is already at higher infectious risk. In this setting, the use of drugs with a mechanism of action alternative to immunosuppression, like thrombopoietin receptor agonists (TRAs), may find particular indication. We report the unique case of a patient with severe immunodeficiency and ITP, who experienced a serious infectious complication while on steroids treatment, and who was successfully treated with Romiplostim second-line. The present experience supports the effectiveness and safety of TRAs as early treatment of ITP patients with drug-induced immunodeficiency or with active infections. PMID:22826792

Palandri, Francesca; Polverelli, Nicola; Lifrieri, Francesca; Catani, Lucia; Giannini, Maria Benedetta; Baccarani, Michele; Vianelli, Nicola

2012-01-01

246

Infection of the choroid plexus by feline immunodeficiency virus  

Microsoft Academic Search

The human, simian, and feline immunodeficiency viruses rapidly penetrate into the brain and trigger an inflammatory process\\u000a that can lead to significant neurologic disease. However, the mechanisms that permit efficient trafficking of macrophage-tropic\\u000a and the more neurotoxic lymphocytotropic isolates are still poorly understood. One potential source of virus entry may be\\u000a the blood-CSF barrier provided by the choroid plexus. Infected

D. C. Bragg; T. A. Childers; M. B. Tompkins; W. A. Tompkins; R. B. Meeker

2002-01-01

247

Lymphoid Organs Function as Major Reservoirs for Human Immunodeficiency Virus  

Microsoft Academic Search

The total number of human immunodeficiency virus type 1 (HIV-1)-infected circulating CD4^+ T lymphocytes is considered to be a reflection of the HIV burden at any given time during the course of HIV infection. However, the low frequency of HIV-infected circulating CD4^+ T lymphocytes and the low level or absence of plasma viremia in the early stages of infection do

Giuseppe Pantaleo; Cecilia Graziosi; Luca Butini; Philip A. Pizzo; Steven M. Schnittman; Donald P. Kotler; Anthony S. Fauci

1991-01-01

248

Inhibition of human immunodeficiency virus type-1 integrase by curcumin  

Microsoft Academic Search

Curcumin (diferuloylmethane) is the yellow pigment in turmeric (Curcuma longa L.) that is widely used as a spice, food coloring (curry) and preservative. Curcumin exhibits a variety of pharmacological effects including antitumor, anti-inflammatory, and anti-infectious activities and is currently in clinical trials for AIDS patients. The effects of curcumin have been determined on purified human immunodeficiency virus type 1 (HIV-1)

Abhijit Mazumder; Krishnamachari Raghavan; John Weinstein; Kurt W. Kohn; Yves Pommier

1995-01-01

249

Gastrointestinal Manifestations in Patients with Common Variable Immunodeficiency  

Microsoft Academic Search

This study focuses on endoscopic and pathologic alterations of gastrointestinal (GI) disorders of Iranian patients with common\\u000a variable immunodeficiency (CVID). Nineteen of 39 CVID patients (48%) had GI complaints. The most common symptom was chronic\\u000a diarrhea (28%). In endoscopic examination of small intestines, 15 patients had no abnormal finding. Duodenal biopsy revealed\\u000a villous atrophy in eight and nodular lymphoid hyperplasia

Ahmad Khodadad; Asghar Aghamohammadi; Nima Parvaneh; Nima Rezaei; Fatemeh Mahjoob; Mohammad Bashashati; Masoud Movahedi; Mohammad Reza Fazlollahi; Fariborz Zandieh; Zahra Roohi; Sina Abdollahzade; Ali Salavati; Ali Kouhi; Bahram Talebpour; Nasser Ebrahimi Daryani

2007-01-01

250

Immunodeficiency and genetic conditions that cause arthritis in childhood  

Microsoft Academic Search

Many conditions can cause or be associated with arthritis in childhood. The authors of this paper will review the situations\\u000a in which underlying immunodeficiency or defective regulation of lymphocyte homeostasis must be suspected, and discuss, for\\u000a some of these diseases, the genetic bases and pathogenesis. In the second part of this article, the authors will focus on\\u000a other diseases that

Pierre Quartier; Anne-Marie Prieur

2002-01-01

251

Interstitial pneumonitis in patients infected with the human immunodeficiency virus  

Microsoft Academic Search

BACKGROUND--A study was performed to identify the clinical, radiographic, and histopathological features of interstitial pneumonitis in patients infected with the human immunodeficiency virus. METHODS--A retrospective review was made of the case notes, chest radiographs, and histopathological results of seven HIV-1 antibody positive patients with symptomatic diffuse pulmonary disease and a pathological diagnosis of non-specific interstitial pneumonitis. RESULTS--All patients had dyspnoea,

M H Griffiths; R F Miller; S J Semple

1995-01-01

252

Thalidomide Inhibits the Replication of Human Immunodeficiency Virus Type 1  

Microsoft Academic Search

Thalidomide, a selective inhibitor of tumor necrosis factor alpha (TNF-alpha) synthesis, suppresses the activation of latent human immunodeficiency virus type 1 (HIV-1) in a monocytoid (U1) line. The inhibition is dose dependent and occurs after exposure of the cells to recombinant TNF-alpha, phorbol myristate acetate, lipopolysaccharide, and other cytokine combinations. Associated with HIV-1 inhibition is a reduction in agonist-induced TNF-alpha

Sanit Makonkawkeyoon; Rhona N. R. Limson-Pobre; Andre L. Moreira; Victoria Schauf; Gilla Kaplan

1993-01-01

253

Tissue tropism of simian immunodeficiency virus in rhesus monkeys  

SciTech Connect

Simian immunodeficiency virus (SIV) is a T-lymphotropic lentivirus that is genetically, immunologically, and morphologically related to the human immunodeficiency viruses type 1 and 2 (HIV-1, HIV-2). In rhesus monkeys, SIV induces a progressively fatal immunodeficiency syndrome strikingly similar to human acquired immunodeficiency syndrome (AIDS). The tissue and cellular tropism of SIV was determined by immunocytochemistry and in situ hybridization using a 3.48 kilobase SIV envelope gene probe labeled with biotin, {sup 35}S, or {sup 3}H. Probes labeled with {sup 35}S nonspecifically bound to tissue eosinophils and produced poor signal resolution compared to tritium labeled probes. Biotin labeled probes did not detect SIV under similar hybridization conditions. Formalin-fixed, paraffin-embedded tissues produced strong hybridization signal with superior morphology compared to frozen tissues. Gastrointestinal, respiratory, and lymphoid tissues most frequently contained SIV RNA. The distribution of SIV did not correlate with sex, or viral inoculum, but was most extensive in animals with SIV induced granulomatous encephalitis. SIV was most frequently observed in lymphocytes and macrophages. In the brain focal granulomas were composed almost entirely of EBM11+, lysozyme+, macrophages which contained large amounts of SIV RNA and p27 core protein detected by the monoclonal antibody R1C7. Cells away from granulomas in the brain parenchyma and around blood vessels contained virus and were compatible with oligodendrocytes and astrocytes. Lymph nodes in follicular hyperplasia contained small numbers of SIV positive cells compatible with lymphocytes in the paracortex and mantle zones as well as in cells of the germinal center. Lymph nodes in various stages of follicular depletion with expanded paracortices contained large numbers of cells with SIV RNA in lymphocytes and macrophages.

Wyand, M.S.

1989-01-01

254

Tuberculous meningitis in patients infected with human immunodeficiency virus  

Microsoft Academic Search

Tuberculosis is the most common opportunistic infection in human immunodeficiency virus (HIV) infected persons. HIV-infected\\u000a patients have a high incidence of tuberculous meningitis as well. The exact incidence and prevalence of tuberculous meningitis\\u000a in HIV-infected patients are not known. HIV infection does not significantly alter the clinical manifestations, laboratory,\\u000a radiographic findings, or the response to therapy. Still, some differences have

Ravindra Kumar Garg; Manish Kumar Sinha

2011-01-01

255

A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but Not Non-Neutralizing Antibodies  

PubMed Central

A desirable but as yet unachieved property of a human immunodeficiency virus type 1 (HIV-1) vaccine candidate is the ability to induce broadly neutralizing antibodies (bNAbs). One approach to the problem is to create trimeric mimics of the native envelope glycoprotein (Env) spike that expose as many bNAb epitopes as possible, while occluding those for non-neutralizing antibodies (non-NAbs). Here, we describe the design and properties of soluble, cleaved SOSIP.664 gp140 trimers based on the subtype A transmitted/founder strain, BG505. These trimers are highly stable, more so even than the corresponding gp120 monomer, as judged by differential scanning calorimetry. They are also homogenous and closely resemble native virus spikes when visualized by negative stain electron microscopy (EM). We used several techniques, including ELISA and surface plasmon resonance (SPR), to determine the relationship between the ability of monoclonal antibodies (MAbs) to bind the soluble trimers and neutralize the corresponding virus. In general, the concordance was excellent, in that virtually all bNAbs against multiple neutralizing epitopes on HIV-1 Env were highly reactive with the BG505 SOSIP.664 gp140 trimers, including quaternary epitopes (CH01, PG9, PG16 and PGT145). Conversely, non-NAbs to the CD4-binding site, CD4-induced epitopes or gp41ECTO did not react with the trimers, even when their epitopes were present on simpler forms of Env (e.g. gp120 monomers or dissociated gp41 subunits). Three non-neutralizing MAbs to V3 epitopes did, however, react strongly with the trimers but only by ELISA, and not at all by SPR and to only a limited extent by EM. These new soluble trimers are useful for structural studies and are being assessed for their performance as immunogens. PMID:24068931

Sanders, Rogier W.; Derking, Ronald; Cupo, Albert; Julien, Jean-Philippe; Yasmeen, Anila; de Val, Natalia; Kim, Helen J.; Blattner, Claudia; de la Peña, Alba Torrents; Korzun, Jacob; Golabek, Michael; de los Reyes, Kevin; Ketas, Thomas J.; van Gils, Marit J.; King, C. Richter; Wilson, Ian A.; Ward, Andrew B.; Klasse, P. J.; Moore, John P.

2013-01-01

256

Comparison of Search Engines Non-Neutral and Neutral Pierre Coucheney  

E-print Network

Comparison of Search Engines Non-Neutral and Neutral Behaviors Pierre Coucheney Inria Rennes to model two situations of a non-neutral search engine behavior, which can rank the link propositions ac Terms Economics, Neutrality, Search engines 1. INTRODUCTION Network neutrality has become a very hot

Paris-Sud XI, Université de

257

Ralstonia pickettii-Induced Ataxia in Immunodeficient Mice  

PubMed Central

We report here the characterization of an asymmetric ataxia syndrome (head tilt and circling, with death in the most severe cases) demonstrated by profoundly immunodeficient mice housed at the Institut Curie SPF facility. The immune system of the affected mice had been genetically modified so that they were deficient in both B and T cells. Extensive bacteriologic, parasitic, serologic, and histopathologic analysis of the affected animals and their healthy controls led us to identify Ralstonia pickettii as the causative agent of the ataxic syndrome. The outbreak was managed through a test-and-cull process. Even though they also carried Ralstonia pickettii, immunocompetent mice that were kept in the same facility, did not show any of the signs that were expressed by their immunodeficient counterparts. This case highlights the difficulty of maintaining immunocompetent and immunodeficient mice in the same microbiologic unit and the importance of enlarging the spectrum of health monitoring to opportunistic agents when investigating clinical cases in populations of immunocompromised rodents. PMID:19389312

Berard, Marion; Medaille, Christine; Simon, Meredith; Serre, Stéphanie; Pritchett-Corning, Kathleen; Dangles-Marie, Virginie

2009-01-01

258

Human monoclonal antibodies that neutralize vaccine and wild-type poliovirus strains.  

PubMed

An essential requirement for eradication of poliomyelitis is the elimination of circulating vaccine derived polioviruses (cVDPV) and polioviruses excreted by chronically infected individuals with immunodeficiencies (iVDPV). As part of a post-eradication risk management strategy, a human monoclonal antibody (mAb) therapeutic could play a role in halting excretion in asymptomatic carriers and could be used, in combination with vaccines and antiviral drugs, to protect polio-exposed individuals. Cross-neutralizing mAbs may be particularly useful, as they would reduce the number of mAbs needed to create a comprehensive PV therapeutic. We cloned a panel of IgG mAbs from OPV-vaccinated, IPV-boosted healthy subjects. Many of the mAbs had potent neutralizing activities against PV wild-type (WT) and Sabin strains, and two of the mAbs, 12F8 and 1E4, were significantly cross-reactive against types 1 and 2 and types 1 and 3, respectively. Mapping the binding epitopes using strains resistant to neutralization (escape mutants) suggested that cross-specific PV binding epitopes may primarily reside within the canyon region, which interacts with the cellular receptor molecule CD155 and the cross-neutralizing chimpanzee/human mAb, A12. Despite their close proximity, the epitopes for the 12F8 and 1E4 mAbs on Sabin 1 were not functionally identical to the A12 epitope. When tested together, 12F8 and 1E4 neutralized a diverse panel of clinically relevant PV strains and did not exhibit interference. Virus mutants resistant to the anti-poliovirus drug V-073 were also neutralized by the mAbs. The 12F8 and 1E4 mAbs may suitable for use as anti-PV therapeutics. PMID:24824031

Puligedda, Rama Devudu; Kouiavskaia, Diana; Adekar, Sharad P; Sharma, Rashmi; Devi Kattala, Chandana; Rezapkin, Gennady; Bidzhieva, Bella; Dessain, Scott K; Chumakov, Konstantin

2014-08-01

259

Investigating antibody neutralization of lyssaviruses using lentiviral pseudotypes: a cross-species comparison.  

PubMed

Cross-neutralization between rabies virus (RABV) and two European bat lyssaviruses (EBLV-1 and -2) was analysed using lentiviral pseudotypes as antigen vectors. Glycoprotein (G-protein) cDNA from RABV challenge virus standard-11 (CVS-11) and EBLV-1 and -2 were cloned and co-expressed with human immunodeficiency virus (HIV) or murine leukemia virus (MLV) gag-pol and packageable green fluorescent protein (GFP) or luciferase reporter genes in human cells. The harvested lentiviral (HIV) vector infected over 40% of baby hamster kidney (BHK) target cells, providing high-titre pseudotype stocks. Tests on blinded antibody-positive (n=15) and -negative (n=45) sera, predetermined by the fluorescent antibody virus neutralization (FAVN) test approved by the World Health Organization (WHO) and Office International des Epizooties (OIE), revealed that the CVS-11 pseudotype assay had 100% concordance with FAVN and strongly correlated with neutralization titres (r2=0.89). Cross-neutralization tests using sera from RABV-vaccinated humans and animals on pseudotypes with CVS-11, EBLV-1 and EBLV-2 envelopes showed that the relative neutralization titres correlated broadly with the degree of G-protein diversity. Pseudotypes have three major advantages over live-virus neutralization tests: (i) they can be handled in low-biohazard-level laboratories; (ii) the use of reporter genes such as GFP or beta-galactosidase will allow the assay to be undertaken at low cost in laboratories worldwide; (iii) each assay requires <10 microl serum. This robust microassay will improve our understanding of the protective humoral immunity that current rabies vaccines confer against emerging lyssaviruses, and will be applicable to surveillance studies, thus helping to control the spread of rabies. PMID:18753230

Wright, Edward; Temperton, Nigel J; Marston, Denise A; McElhinney, Lorraine M; Fooks, Anthony R; Weiss, Robin A

2008-09-01

260

In Vivo Distribution of the Human Immunodeficiency Virus\\/Simian Immunodeficiency Virus Coreceptors: CXCR4, CCR3, and CCR5  

Microsoft Academic Search

We have evaluated the in vivo distribution of the major human immunodeficiency virus\\/simian immunode- ficiency virus (HIV\\/SIV) coreceptors, CXCR4, CCR3, and CCR5, in both rhesus macaques and humans. T lymphocytes and macrophages in both lymphoid and nonlymphoid tissues are the major cell populations expressing HIV\\/SIV coreceptors, reaffirming that these cells are the major targets of HIV\\/SIV infection in vivo. In

LINQI ZHANG; TIAN HE; ANDREW TALAL; GLORIA WANG; SARAH S. FRANKEL

261

Epstein-Barr and human immunodeficiency viruses in acquired immunodeficiency syndrome-related primary central nervous system lymphoma.  

PubMed Central

The prevalence of Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV) in acquired immunodeficiency syndrome (AIDS)-related primary central nervous system (CNS) lymphoma was examined. Deoxyribonucleic acid (DNA) extracted from 12 formalin-fixed, paraffin-embedded tumors was used as substrate for the polymerase chain reaction (PCR). Targets for amplification were the EBNA-1 region of EBV, the gag region of HIV, and a single copy cellular sequence as a control. The cases studied were autopsy and surgical specimens collected between the years 1985 and 1989. By the working formulation for non-Hodgkin's lymphomas, five had large cell, four had mixed large and small cleaved cell, two had small cleaved cell, and one had an unclassified histology. Epstein-Barr virus was detected in 6 of 12 tumors studied. Human immunodeficiency virus was not detected in any of the tumors. The presence of EBV was not correlated with any particular histologic tumor type. It is concluded that EBV, not HIV, can be detected in a large percentage (50%) of AIDS-related primary central nervous system (CNS) lymphomas. This viral association may be significant in light of the demonstrated ability of EBV to induce lymphoid tumors in experimental mammalian systems. Images Figure 1 Figure 2 PMID:1323221

Morgello, S.

1992-01-01

262

Neutralization kinetics for polonium-218  

SciTech Connect

In a well-defined experimental system the neutralization of polonium-218 ions was investigated as a function of the physical and chemical properties of the controlled composition atmosphere. The diffusion coefficient of polonium-218 under various concentrations of trace gas NO/sub 2/ in nitrogen was measured. The mobilities of Po/sup +/ and PoO/sub 2//sup +/ are determined by combining experimental results with a computer model of the system. Three neutralization mechanisms were individually studied. The small-ion recombination rate has been found to be proportional to the square root of radon concentration. The electron-scavenging mechanism is responsible for the neutralization of Po/sup +/ in NO/sub 2/ or H/sub 2/O in nitrogen. When PoO/sub 2//sup +/ is formed, the electron-transfer mechanism dominates the neutralization process. The electron is transferred to PoO/sub 2//sup +/ from molecules with lower ionization potentials. The ionization molecules with lower ionization potentials. The ionization potential of PoO/sub 2//sup +/ is also determined to be 10.44 +/- 0.05 eV.

Chu, K.D.; Hopke, P.K.

1988-06-01

263

Progress on the induction of neutralizing antibodies against HIV-1  

PubMed Central

The Human Immunodeficiency Virus Type -1 (HIV-1), the causative agent of AIDS in humans, is one of the most catastrophic pandemics to affect human health care in the latter 20th century. The best hope of controlling this pandemic is the development of a successful prophylactic vaccine. However, to date, this goal has proven to be exceptionally elusive. The recent failure of an experimental AIDS vaccine in a phase IIb study named the STEP trial, intended to solely elicit cell mediated immune responses against HIV-1, has highlighted the need for a balanced immune response consisting of not only cellular immunity but also a broad and potent antibody response which can prevent the infection of HIV-1. This article will review the efforts being made up to this point to elicit such antibody responses, especially with regards to the use of a DNA prime-protein boost regimen which has been proven to be a highly effective platform for the induction of neutralizing antibodies in both animal and early phase human studies. PMID:19627166

Vaine, Michael; Lu, Shan; Wang, Shixia

2013-01-01

264

Mode of action of SDZ NIM 811, a nonimmunosuppressive cyclosporin A analog with activity against human immunodeficiency virus (HIV) type 1: interference with HIV protein-cyclophilin A interactions.  

PubMed Central

Cyclosporins, in particular the nonimmunosuppressive derivative SDZ NIM 811, exhibit potent anti-human immunodeficiency virus type 1 (HIV-1) activity in vitro. SDZ NIM 811 interferes at two stages of the viral replication cycle: (i) translocation of the preintegration complex to the nucleus and (ii) production of infectious virus particles. Immunosuppressive activity is not correlated with anti-HIV-1 activity of cyclosporins. However, binding to cyclophilin A, the major cellular receptor protein of cyclosporins, is a prerequisite for HIV inhibition: all structural changes of the cyclosporin A molecule leading to loss of affinity to cyclophilin abolished the antiviral effect. Cyclosporin derivatives did not interact directly with HIV-1 proteins; cyclophilin was the only detectable receptor protein for antivirally active cyclosporins. There is no evidence that inhibition of HIV occurs via a gain of function of cyclophilin in the presence of cyclosporins: the complex of cyclophilin A with SDZ NIM 811 does not bind to calcineurin or to any other viral or cellular proteins under conditions in which calcineurin binding to the cyclophilin A-cyclosporin A complex is easily detectable. Thus, the loss of function caused by binding of cyclosporins to cyclophilin seems to be sufficient for the anti-HIV effect. Cyclophilin A was demonstrated to bind to HIV-1 p24gag, and the formation of complexes was blocked by cyclosporins with 50% inhibitory concentrations of about 0.7 microM. HIV-2 and simian immunodeficiency virus are only weakly or not at all inhibited by cyclosporins. For gag-encoded proteins derived from HIV-1, HIV-2, or simian immunodeficiency virus particles, cyclophilin-binding capacity correlated with sensitivity of the viruses to inhibition by cyclosporins. Cyclophilin A also binds to HIV-1 proteins other than gag-encoded proteins, namely, p17gag, Nef, Vif, and gp120env; the biological significance of these interactions is questionable. We conclude that HIV-1 Gag-cyclophilin A interaction may be essential in HIV-1 replication, and interference with this interaction may be the molecular basis for the antiviral activity of cyclosporins. PMID:7884893

Billich, A; Hammerschmid, F; Peichl, P; Wenger, R; Zenke, G; Quesniaux, V; Rosenwirth, B

1995-01-01

265

Amygdala activation in the processing of neutral faces in social anxiety disorder: Is neutral really neutral?  

Microsoft Academic Search

Previous research has suggested that Social Anxiety Disorder (SAD) is associated with a tendency to interpret ambiguous social stimuli in a threatening manner. The present study used event-related functional magnetic resonance imaging to examine patterns of neural activation in response to the processing of neutral facial expressions in individuals diagnosed with SAD and healthy controls (CTLs). The SAD participants exhibited

Rebecca E. Cooney; Lauren Y. Atlas; Jutta Joormann; Fanny Eugène; Ian H. Gotlib

2006-01-01

266

38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...  

Code of Federal Regulations, 2011 CFR

...human immunodeficiency virus to public health authorities. 1.486 Section...human immunodeficiency virus to public health authorities. (a) In the...to a Federal, State, or local public health authority, charged under...

2011-07-01

267

38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...  

Code of Federal Regulations, 2010 CFR

...human immunodeficiency virus to public health authorities. 1.486 Section...human immunodeficiency virus to public health authorities. (a) In the...to a Federal, State, or local public health authority, charged under...

2010-07-01

268

38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...  

Code of Federal Regulations, 2013 CFR

...human immunodeficiency virus to public health authorities. 1.486 Section...human immunodeficiency virus to public health authorities. (a) In the...to a Federal, State, or local public health authority, charged under...

2013-07-01

269

38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...  

...human immunodeficiency virus to public health authorities. 1.486 Section...human immunodeficiency virus to public health authorities. (a) In the...to a Federal, State, or local public health authority, charged under...

2014-07-01

270

38 CFR 1.486 - Disclosure of information related to infection with the human immunodeficiency virus to public...  

Code of Federal Regulations, 2012 CFR

...human immunodeficiency virus to public health authorities. 1.486 Section...human immunodeficiency virus to public health authorities. (a) In the...to a Federal, State, or local public health authority, charged under...

2012-07-01

271

75 FR 22814 - Guidance for Industry: Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1...  

Federal Register 2010, 2011, 2012, 2013

...Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV): Testing...Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV): Testing...serologic testing for markers of HIV-1 and HCV infection on samples,...

2010-04-30

272

Selective Modification of Variable Loops Alters Tropism and Enhances Immunogenicity of Human Immunodeficiency Virus Type 1 Envelope  

PubMed Central

Although the B clade of human immunodeficiency virus type 1 (HIV-1) envelopes (Env) includes five highly variable regions, each of these domains contains a subset of sequences that remain conserved. The V3 loop has been much studied for its ability to elicit neutralizing antibodies, which are often restricted to a limited number of closely related strains, likely because a large number of antigenic structures are generated from the diverse amino acid sequences in this region. Despite these strain-specific determinants, subregions of V3 are highly conserved, and the effects of different portions of the V3 loop on Env tropism and immunogenicity have not been well delineated. For this report, selective deletions in V3 were introduced by shortening of the stem of the V3 loop. These mutations were explored in combination with deletions of selected V regions. Progressive shortening of the stem of V3 abolished the immunogenicity as well as the functional activity of HIV Env; however, two small deletions on both arms of the V3 stem altered the tropism of the dualtropic 89.6P viral strain so that it infected only CXCR4+ cells. When this smaller deletion was combined with removal of the V1 and V2 loops and used as an immunogen in guinea pigs, the antisera were able to neutralize multiple independent clade B isolates with a higher potency. These findings suggest that highly conserved subregions within V3 may be relevant targets for eliciting neutralizing antibody responses, affecting HIV tropism, and increasing the immunogenicity of AIDS vaccines. PMID:15047819

Yang, Zhi-yong; Chakrabarti, Bimal K.; Xu, Ling; Welcher, Brent; Kong, Wing-pui; Leung, Kwanyee; Panet, Amos; Mascola, John R.; Nabel, Gary J.

2004-01-01

273

Plasma/Neutral-Beam Etching Apparatus  

NASA Technical Reports Server (NTRS)

Energies of neutral particles controllable. Apparatus developed to produce intense beams of reactant atoms for simulating low-Earth-orbit oxygen erosion, for studying beam-gas collisions, and for etching semiconductor substrates. Neutral beam formed by neutralization and reflection of accelerated plasma on metal plate. Plasma ejected from coaxial plasma gun toward neutralizing plate, where turned into beam of atoms or molecules and aimed at substrate to be etched.

Langer, William; Cohen, Samuel; Cuthbertson, John; Manos, Dennis; Motley, Robert

1989-01-01

274

Variability of clinical and immunological phenotype in immunodeficiency-centromeric instability-facial anomalies syndrome  

Microsoft Academic Search

Immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome is a condition characterized by variable combined immunodeficiency, developmental delay, facial anomalies and a variety of structural chromosomal rearrangements. Recently, aberrations at the molecular level have been described consisting of alterations in the methylation pattern of classical satellite DNA. To our knowledge 15 subjects have been described so far in the literature showing marked phenotypic

P. Franceschini; S. Martino; M. Ciocchini; E. Ciuti; M. P. Vardeu; A. Guala; F. Signorile; P. Camerano; D. Franceschini; P. A. Tovo

1995-01-01

275

Clinical and Immunological Features of 65 Iranian Patients with Common Variable Immunodeficiency  

Microsoft Academic Search

Common variable immunodeficiency (CVID) is a primary immunodeficiency disease characterized by hy- pogammaglobulinemia and recurrent bacterial infections. The records of 65 patients with CVID (37 males and 28 females) in the age range of 24 to 537 months were reviewed. By the year 2003, 11 patients had died and seven patients could not be located. The total follow-up period was

Asghar Aghamohammadi; Abolhasan Farhoudi; Mostafa Moin; Nima Rezaei; Ali Kouhi; Zahra Pourpak; N. Yaseri; M. Movahedi; M. Gharagozlou; F. Zandieh; F. Yazadni; S. Arshi; I. MohammadZadeh; B. M. Ghazi; M. Mahmoudi; S. Tahaei; A. Isaeian

2005-01-01

276

Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity  

Microsoft Academic Search

Recent studies of human immunodeficiency virus type 1 (HIV-1) infection in humans and of simian immunodeficiency virus (SIV) in rhesus monkeys have shown that resolution of the acute viral infection and control of the subsequent persistent infection are mediated by the antiviral cellular immune response. We comparatively assessed several vaccine vector delivery systems-three formulations of a plasmid DNA vector, the

John W. Shiver; Tong-Ming Fu; Ling Chen; Danilo R. Casimiro; Mary-Ellen Davies; Robert K. Evans; Zhi-Qiang Zhang; Adam J. Simon; Wendy L. Trigona; Sheri A. Dubey; Lingyi Huang; Virginia A. Harris; Romnie S. Long; Xiaoping Liang; Larry Handt; William A. Schleif; Lan Zhu; Daniel C. Freed; Natasha V. Persaud; Liming Guan; Kara S. Punt; Aimin Tang; Minchun Chen; Keith A. Wilson; Kelly B. Collins; Gwendolyn J. Heidecker; V. Rose Fernandez; Helen C. Perry; Joseph G. Joyce; Karen M. Grimm; James C. Cook; Paul M. Keller; Denise S. Kresock; Henryk Mach; Robert D. Troutman; Lynne A. Isopi; Donna M. Williams; Zheng Xu; Kathryn E. Bohannon; David B. Volkin; David C. Montefiori; Ayako Miura; Georgia R. Krivulka; Michelle A. Lifton; Marcelo J. Kuroda; Jörn E. Schmitz; Norman L. Letvin; Michael J. Caulfield; Andrew J. Bett; Rima Youil; David C. Kaslow; Emilio A. Emini

2002-01-01

277

AIDS . Author manuscript Non-AIDS-defining deaths and immunodeficiency in the era of combination  

E-print Network

AIDS . Author manuscript Page /1 12 Non-AIDS-defining deaths and immunodeficiency in the era immunodeficiency is associated with the most frequent non-AIDS-defining causes of death, in the era of combination (71,230 person-years follow-up), 597 died, 333 (55.7 ) from non-AIDS-defining causes. Non-AIDS

Paris-Sud XI, Université de

278

New Strain of Simian Immunodeficiency Virus Identified in Wild-Born Chimpanzees from Central Africa  

E-print Network

New Strain of Simian Immunodeficiency Virus Identified in Wild-Born Chimpanzees from Central Africa Identified in Wild-Born Chimpanzees from Central Africa. PLoS ONE 7(9): e44298. doi:10.1371/journal of simian immunodeficiency viruses (SIVs) and the origin and emergence of HIV since chimpanzees in west­central

Boyer, Edmond

279

Recent key advances in human immunodeficiency virus medicine and implications for China  

Microsoft Academic Search

In this article we summarize several recent major developments in human immunodeficiency virus treatment, prevention, outcome, and social policy change. Updated international guidelines endorse more aggressive treatment strategies and safer antiretroviral drugs. New antiretroviral options are being tested. Important lessons were learned in the areas of human immunodeficiency virus vaccines and microbicide gels from clinical studies, and additional trials in

Kai Sun; Shuntai Zhou; Ray Y Chen; Myron S Cohen; Fujie Zhang

2010-01-01

280

Increased expression of interferon-inducible genes in macaque lung tissues during simian immunodeficiency virus infection  

Microsoft Academic Search

Pulmonary infections and dysfunction are frequent outcomes during the development of immunodeficiency associated with human immunodeficiency virus type 1 (HIV-1) infection, and obtaining a better understanding of the immunologic changes that occur in lungs following HIV-1 infection will provide a foundation for the development of further intervention strategies. We sought here to identify changes in the pulmonary immune environment that

Todd M. Schaefer; Craig L. Fuller; Shrabani Basu; Beth A. Fallert; Sandra L. Poveda; Sonali K. Sanghavi; Yang-Kyu Choi; Denise E. Kirschner; Eleanor Feingold; Todd A. Reinhart

2006-01-01

281

Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma in a Patient with Common Variable Immunodeficiency Syndrome  

Microsoft Academic Search

Common variable immunodeficiency syndrome (CVID) is a primary immunodeficiency typically presenting with recurrent sinopulmonary infections. Non-Hodgkin’s lymphoma and other secondary cancers are typical late complications of CVID. We report on a patient suffering from CVID with a history of recurrent sinopulmonary infections, interstitial pulmonary changes and hepatic granulomas. Despite treatment with intravenous immunoglobulin followed by a reduction in the number

F. Reichenberger; C. Wyser; M. Gonon; G. Cathomas; M. Tamm

2001-01-01

282

Clinical manifestation of mannose-binding lectin deficiency in adults independent of concomitant immunodeficiency  

Microsoft Academic Search

Mannose-binding lectin (MBL) mediates important functions within the innate immune system, and its deficiency was associated with infectious complications. However, in adults without concomitant immunodeficiency the clinical relevance of MBL deficiency remains controversial. We analyzed the distribution of MBL deficiency and its association with concomitant immunodeficiency in 228 adult Caucasian patients with a history of recurrent and\\/or severe infections. Two

Conny Hoeflich; Nadine Unterwalder; Sabine Schuett; Kathrin Schmolke; Olaf Boenisch; Markus Hammer; Ramona Scheufele; Dagmar Michael; Hans-Dieter Volk; Carmen Scheibenbogen; Volker von Baehr; Christian Meisel

2009-01-01

283

Amplification of a Complete Simian Immunodeficiency Virus Genome from Fecal RNA of a Wild Chimpanzee  

Microsoft Academic Search

Current knowledge of the genetic diversity of simian immunodeficiency virus (SIVcpz) infection of wild chimpanzees (Pan troglodytes) is incomplete since few isolates, mostly from captive apes from Cameroon and Gabon, have been characterized; yet this information is critical for understanding the origins of human immunodeficiency virus type 1 (HIV-1) and the circumstances leading to the HIV-1 pandemic. Here, we report

Mario L. Santiago; Frederic Bibollet-Ruche; Elizabeth Bailes; Shadrack Kamenya; Martin N. Muller; Magdalena Lukasik; Anne E. Pusey; D. Anthony Collins; Richard W. Wrangham; Jane Goodall; George M. Shaw; Paul M. Sharp; Beatrice H. Hahn

2003-01-01

284

Neutralization kinetics for polonium-218  

Microsoft Academic Search

In a well-defined experimental system the neutralization of polonium-218 ions was investigated as a function of the physical and chemical properties of the controlled composition atmosphere. The diffusion coefficient of polonium-218 under various concentrations of trace gas NOâ in nitrogen was measured. The mobilities of Po\\/sup +\\/ and PoOâ\\/sup +\\/ are determined by combining experimental results with a computer model

Kai Dee Chu; Philip K. Hopke

1988-01-01

285

Optimization of Neutral Atom Imagers  

NASA Technical Reports Server (NTRS)

The interactions between plasma structures and neutral atom populations in interplanetary space can be effectively studied with energetic neutral atom imagers. For neutral atoms with energies less than 1 keV, the most efficient detection method that preserves direction and energy information is conversion to negative ions on surfaces. We have examined a variety of surface materials and conversion geometries in order to identify the factors that determine conversion efficiency. For chemically and physically stable surfaces smoothness is of primary importance while properties such as work function have no obvious correlation to conversion efficiency. For the noble metals, tungsten, silicon, and graphite with comparable smoothness, conversion efficiency varies by a factor of two to three. We have also examined the way in which surface conversion efficiency varies with the angle of incidence of the neutral atom and have found that the highest efficiencies are obtained at angles of incidence greater then 80deg. The conversion efficiency of silicon, tungsten and graphite were examined most closely and the energy dependent variation of conversion efficiency measured over a range of incident angles. We have also developed methods for micromachining silicon in order to reduce the volume to surface area over that of a single flat surface and have been able to reduce volume to surface area ratios by up to a factor of 60. With smooth micro-machined surfaces of the optimum geometry, conversion efficiencies can be increased by an order of magnitude over instruments like LENA on the IMAGE spacecraft without increase the instruments mass or volume.

Shappirio, M.; Coplan, M.; Balsamo, E.; Chornay, D.; Collier, M.; Hughes, P.; Keller, J.; Ogilvie, K.; Williams, E.

2008-01-01

286

Pediatric autoimmune enteropathy: an entity frequently associated with immunodeficiency disorders.  

PubMed

The term pediatric autoimmune enteropathy was originally applied to a form of intractable diarrhea seen in children under the age of 6 months and characterized by male predominance, concurrent autoimmune-associated disorders, circulating gut autoantibodies, a lack of severe immunodeficiency and small bowel atrophy with prominent crypt apoptosis. However, recent studies have cast doubt over the specific clinicopathologic findings associated with this entity. We, therefore, collected 178 gastrointestinal biopsies from 14 patients and examined their clinical, serologic and pathologic findings. Patients at presentation ranged in age from birth to 15.9 years (median, 5.5 months; mean, 4.1 years) and included six males and eight females. All children suffered from chronic watery diarrhea and malnutrition. Concomitant-associated disorders were noted in 11 (79%) cases and included 10 (71%) with an immunodeficiency disorder and/or another autoimmune-related disease. Eleven patients (79%) were positive for anti-enterocyte antibodies. The salient findings of autoimmune enteropathy were most prominent in the small intestines and the majority (79%) of patients demonstrated villous blunting, crypt hyperplasia, mononuclear cell inflammatory expansion of the lamina propria and crypt apoptosis. The remaining (21%) patients showed marked intraepithelial lymphocytosis reminiscent of celiac disease. Further, acute cryptitis and crypt abscesses were seen in seven (50%) patients obscuring the presence of apoptosis. The absence of Paneth cells, goblet cells or both was noted in seven (50%) patients. Follow-up information was available for all patients with 13 (93%) receiving immunosuppressant therapy and demonstrating partial-to-complete response. In total, three patients died from continued diarrhea and sepsis with one decedent before treatment could be initiated. In summary, autoimmune enteropathy in children is a heterogenous disease with protean clinical and pathologic findings. Although anti-enterocyte antibodies were identified in the majority of the cases, their presence was variable and insensitive. In addition, pediatric autoimmune enteropathy was frequently encountered in the setting of immunodeficiency disorders. PMID:24051695

Singhi, Aatur D; Goyal, Alka; Davison, Jon M; Regueiro, Miguel D; Roche, Robyn L; Ranganathan, Sarangarajan

2014-04-01

287

Atmospheric neutral density experiment (ANDE)  

NASA Astrophysics Data System (ADS)

The Atmospheric Neutral Density Experiment (ANDE) is a mission proposed by the Naval Research laboratory to monitor the thermospheric neutral density at an altitude of 400km. The mission objectives are to provide total neutral density along the orbit for improved orbit determination of resident space objects. The measurements also provide a critical validation point for the upcoming Special Sensor Ultraviolet Limb Imagers (SSULI) to be launched on each of the five Defense Meteorological Satellite Program (DMSP) spacecraft in block 5D3 starting in 2001. In addition ANDE provides two calibration objects for use in the Air Force High Accuracy Satellite Drag Model (HASDM) initiative to help maintain and improve accuracy of the space object catalog. The mission consists of two spherical satellites fitted with retro-reflectors for satellite laser ranging (SLR). One satellite is completely passive, the other carries active instrumentation to measure the partial pressure of atmospheric constituents, GPS positioning, acceleration in all 3 axes, and surface temperature. The active satellite will be fitted with modulating retro-reflectors. The spacecraft telemetry will be transferred to the ground by modulating and reflecting the SLR laser interrogation beam.

Nicholas, Andrew C.; Thonnard, Stefan E.

2002-01-01

288

Combined immunodeficiency with abnormal expression of MHC class II genes.  

PubMed

The MHC class II CID represents an example of immunodeficiency in which the defect in expression of membrane glycoproteins leads to abnormal cell to cell interactions and thus to abnormal immune responses. It represents an interesting model which confirms the importance of MHC molecules in all immune responses to foreign antigens. It also underlines the complexity of regulatory mechanism which control the expression of MHC class II genes. To elucidate these mechanisms, it is essential to identify and characterize the genes involved in control of MHC class II expression. PMID:2463126

Griscelli, C; Lisowska-Grospierre, B; Le Deist, F; Durandy, A; Marcadet, A; Fischer, A; de Preval, C; Mach, B

1989-01-01

289

Immunodeficiency associated with a nonsense mutation of IKBKB.  

PubMed

We report an infant of consanguineous parents of Turkish decent with a novel immunodeficiency associated with homozygosity for a nonsense mutation of the gene encoding Inhibitor of nuclear factor kappa-B (NF-?B) kinase subunit beta (IKK?). At five months, she presented with respiratory insufficiency and Pneumocystis jirovecii pneumonia which was successfully treated. At nine months, iatrogenic systemic infection with Mycobacterium bovis was found and eventually led to her death at age 14 months. Laboratory findings were reminiscent of hyper-IgM syndrome, but genetic testing gave no explanation before whole exome sequencing revealed a novel mutation abrogating signaling through the canonical NF-?B pathway. PMID:25216719

Nielsen, Christian; Jakobsen, Marianne A; Larsen, Martin Jakob; Müller, Amanda C; Hansen, Soren; Lillevang, Søren T; Fisker, Niels; Barington, Torben

2014-11-01

290

Human Immunodeficiency Virus Infection: The Spectrum Beyond AIDS  

PubMed Central

Since 1981, the Acquired Immune Deficiency Syndrome (AIDS) has emerged as the major infectious epidemic of our time. It is the most profound manifestation of infection with the Human Immunodeficiency Virus (HIV). Since 1984, serologic methods have existed to detect antibody to HIV. Several other clinical entities have been detected and are attributable to HIV infection. Appropriate counsel must accompany antibody testing. The author discusses the acute seroconversion event, as well as asymptomatic carrier status, including generalized lymphadenopathy. He also reviews the symptomatic states that do not meet the surveillance definition of AIDS, including treatments where available. PMID:21263801

Willoughby, Brain C.

1987-01-01

291

Human Immunodeficiency Virus gag and protease: partners in resistance  

E-print Network

in resi Axel Fun1, Annemarie MJ Wensing1, Jens Verheyen2 and Abstract Human Immunodeficiency Virus (HIV) maturation plays an generation of mature infectious virus particles through pr proteins. An impaired polyprotein processing results in th Consequently... or enhance the rate of cleavage by the viral protease. J Virol 2002, 76:10226–10233. 9. Maguire MF, Guinea R, Griffin P, Macmanus S, Elston RC, Wolfram J, Richards N, Hanlon MH, Porter DJ, Wrin T, Parkin N, Tisdale M, Furfine E, Petropoulos C, Snowden BW...

Fun, Axel; Wensing, Annemarie MJ; Verheyen, Jens; Nijhuis, Monique

2012-08-06

292

Alteration in pancreatic islet function in human immunodeficiency virus.  

PubMed

Molecular mechanisms behind the defects in insulin production and secretion associated with antihuman immunodeficiency virus (anti-HIV) therapy and the development of HIV-associated lipodystrophy syndrome (HALS) are discussed in this article. Data suggesting insulin resistance on the beta cell and defects in first-phase insulin release of HALS patients are presented. Hepatic extraction of insulin, nonglucose insulin secretagogues and insulin-like growth factor release may exert influence on the demand of circulating insulin and on insulin secretion in HIV-infected patients. Finally, the paucity in understanding the incretin effects in HIV and HIV therapy in relation to insulin secretion is highlighted. PMID:25169562

Haugaard, Steen B

2014-09-01

293

Severe combined immunodeficiency with T lymphocytes retaining functional activity.  

PubMed

Two cases of severe combined immunodeficiency (SCID) with normal numbers of T cells are reported. Studies of T-cell subsets showed an absence of TQ1+ lymphocytes and a very low percentage of CD4+ cells in Patient 2. Functional studies of T cells from this patient showed a normal suppressor activity. Patient 1 had normal percentages of T-cell subsets and his lymphocytes showed helper and suppressor activities but to a lesser degree than normal controls. Both cases stressed the heterogeneity of SCID in which T cells could be present and retain some of their functional activities. PMID:3257433

Fontán, G; García Rodriguez, M C; Carrasco, S; Zabay, J M; de la Concha, E G

1988-03-01

294

The Human Immunodeficiency Virus: Infectivity and Mechanisms of Pathogenesis  

NASA Astrophysics Data System (ADS)

Infection with the human immunodeficiency virus (HIV) results in a profound immunosuppression due predominantly to a selective depletion of helper/inducer T lymphocytes that express the receptor for the virus (the CD4 molecule). HIV also has tropism for the brain leading to neuropsychiatric abnormalities. Besides inducing cell death, HIV can interfere with T4 cell function by various mechanisms. The monocyte serves as a reservoir for HIV and is relatively refractory to its cytopathic effects. HIV can exist in a latent or chronic form which can be converted to a productive infection by a variety of inductive signals.

Fauci, Anthony S.

1988-02-01

295

Recent developments in human immunodeficiency virus-1 latency research  

PubMed Central

Almost 30 years after its initial discovery, infection with the human immunodeficiency virus-1 (HIV-1) remains incurable and the virus persists due to reservoirs of latently infected CD4+ memory T-cells and sanctuary sites within the infected individual where drug penetration is poor. Reactivating latent viruses has been a key strategy to completely eliminate the virus from the host, but many difficulties and unanswered questions remain. In this review, the latest developments in HIV-persistence and latency research are presented. PMID:23364195

Dietrich, Isabelle; Hosie, Margaret J.; Willett, Brian J.

2013-01-01

296

Neutral beamline with improved ion energy recovery  

DOEpatents

A neutral beamline employing direct energy recovery of unneutralized residual ions is provided which enhances the energy recovery of the full energy ion component of the beam exiting the neutralizer cell, and thus improves the overall neutral beamline efficiency. The unneutralized full energy ions exiting the neutralizer are deflected from the beam path and the electrons in the cell are blocked by a magnetic field applied transverse to the beam direction in the neutral izer exit region. The ions which are generated at essentially ground potential and accelerated through the neutralizer cell by a negative acceleration voltage are collected at ground potential. A neutralizer cell exit end region is provided which allows the magnetic and electric fields acting on the exiting ions to be loosely coupled. As a result, the fractional energy ions exiting the cell are reflected onto and collected at an interior wall of the neutralizer formed by the modified end geometry, and thus do not detract from the energy recovery efficiency of full energy ions exiting the cell. Electrons within the neutralizer are prevented from exiting the neutralizer end opening by the action of crossed fields drift (ExB) and are terminated to a collector collar around the downstream opening of the neutralizer. The correct combination of the extended neutralizer end structure and the magnet region is designed so as to maximize the exit of full energy ions and to contain the fractional energy ions.

Kim, Jinchoon (San Diego, CA)

1984-01-01

297

Imaging space plasmas in energetic neutral atoms  

Microsoft Academic Search

Many space plasmas contain energetic singly-charged ions immersed in a cold gas of neutral atoms and molecules. When the energetic ions undergo charge-exchange collisions with the background cold neutrals, they become energetic neutral atoms (ENAs). Thus the space plasma Â\\

E. C. Roelof; R. Demajistre; D. G. Mitchell; P. C Son Brandt

2004-01-01

298

Selectionism and Neutralism in Molecular Evolution  

Microsoft Academic Search

Charles Darwin proposed that evolution occurs primarily by natural selection, but this view has been controversial from the beginning. Two of the major opposing views have been mutationism and neutralism. Early molecular studies suggested that most amino acid substitutions in proteins are neutral or nearly neutral and the functional change of proteins occurs by a few key amino acid substitutions.

Masatoshi Nei

2005-01-01

299

The Net Neutrality Debate: The Basics  

ERIC Educational Resources Information Center

Rich Greenfield examines the basics of today's net neutrality debate that is likely to be an ongoing issue for society. Greenfield states the problems inherent in the definition of "net neutrality" used by Common Cause: "Network neutrality is the principle that Internet users should be able to access any web content they choose and use any…

Greenfield, Rich

2006-01-01

300

A Nucleotide Substitution in the tRNALys Primer Binding Site Dramatically Increases Replication of Recombinant Simian Immunodeficiency Virus Containing a Human Immunodeficiency Virus Type 1 Reverse Transcriptase  

Microsoft Academic Search

A recombinant simian immunodeficiency virus (SIV) derived from strain 239 (SIVmac239) with reverse transcriptase (RT) sequences from human immunodeficiency virus type 1 (HIV-1) strain HXB2 was severely impaired for replication. Detectable p27Gag levels were not observed until day 65 and peak p27Gag levels were not reached until day 75 after transfection of CEMx174 cells with the recombinant DNA. Sequences from

Kelly Soderberg; Lynn Denekamp; Sarah Nikiforow; Karen Sautter; Ronald C. Desrosiers; Louis Alexander

2002-01-01

301

Efavirenz Therapy in Rhesus Macaques Infected with a Chimera of Simian Immunodeficiency Virus Containing Reverse Transcriptase from Human Immunodeficiency Virus Type 1  

Microsoft Academic Search

The specificity of nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) for the RT of human immunodeficiency virus type 1 (HIV-1) has prevented the use of simian immunodeficiency virus (SIV) in the study of NNRTIs and NNRTI-based highly active antiretroviral therapy. However, a SIV-HIV-1 chimera (RT-SHIV), in which the RT from SIVmac239 was replaced with the RT-encoding region from HIV-1, is susceptible

Michael J. Hofman; Joanne Higgins; Timothy B. Matthews; Niels C. Pedersen; Chalet Tan; Raymond F. Schinazi; Thomas W. North

2004-01-01

302

Simian immunodeficiency virus encephalitis in the white matter and degeneration of the cerebral cortex occur independently in simian immunodeficiency virus-infected monkey  

Microsoft Academic Search

Highly active antiretroviral therapy (HAART) has been successful to reduce progression of acquired immunodeficiency syndrome\\u000a (AIDS). Nevertheless, recent autopsy analysis of the brain from patients with human immunodeficiency virus (HIV)-1 infection\\u000a reported same or even increasing numbers of AIDS encephalopathy. This insufficient effect of HAART for central nervous system\\u000a (CNS) complication might be explained by independent pathogenetic processes in lymph

Hui Qin Xing; Takashi Moritoyo; Kazuyasu Mori; Kei Tadakuma; Chie Sugimoto; Fumiko Ono; Hitoshi Hayakawa; Shuji Izumo

2003-01-01

303

env Sequences of Simian Immunodeficiency Viruses from Chimpanzees in Cameroon Are Strongly Related to Those of Human Immunodeficiency Virus Group N from the Same Geographic Area  

Microsoft Academic Search

Human immunodeficiency virus type 1 (HIV-1) group N from Cameroon is phylogenetically close, in env ,t o the simian immunodeficiency virus (SIV) cpz-gab from Gabon and SIVcpz-US of unknown geographic origin. We screened 29 wild-born Cameroonian chimpanzees and found that three (Cam3, Cam4, and Cam5) were positive for HIV-1 by Western blotting. Mitochondrial DNA sequence analysis demonstrated that Cam3 and

SYLVIE CORBET; MICHAELA C. MULLER-TRUTWIN; PIERRE VERSMISSE; SEVERINE DELARUE; AHIDJO AYOUBA; JOHN LEWIS; SOREN BRUNAK; PAUL MARTIN; FRANCOISE BRUN-VEZINET; FRANCOIS SIMON; FRANCOISE BARRE-SINOUSSI; PHILIPPE MAUCLERE

2000-01-01

304

Selective Expansion of Viral Variants following Experimental Transmission of a Reconstituted Feline Immunodeficiency Virus Quasispecies  

PubMed Central

Following long-term infection with virus derived from the pathogenic GL8 molecular clone of feline immunodeficiency virus (FIV), a range of viral variants emerged with distinct modes of interaction with the viral receptors CD134 and CXCR4, and sensitivities to neutralizing antibodies. In order to assess whether this viral diversity would be maintained following subsequent transmission, a synthetic quasispecies was reconstituted comprising molecular clones bearing envs from six viral variants and its replicative capacity compared in vivo with a clonal preparation of the parent virus. Infection with either clonal (Group 1) or diverse (Group 2) challenge viruses, resulted in a reduction in CD4+ lymphocytes and an increase in CD8+ lymphocytes. Proviral loads were similar in both study groups, peaking by 10 weeks post-infection, a higher plateau (set-point) being achieved and maintained in study Group 1. Marked differences in the ability of individual viral variants to replicate were noted in Group 2; those most similar to GL8 achieved higher viral loads while variants such as the chimaeras bearing the B14 and B28 Envs grew less well. The defective replication of these variants was not due to suppression by the humoral immune response as virus neutralising antibodies were not elicited within the study period. Similarly, although potent cellular immune responses were detected against determinants in Env, no qualitative differences were revealed between animals infected with either the clonal or the diverse inocula. However, in vitro studies indicated that the reduced replicative capacity of variants B14 and B28 in vivo was associated with altered interactions between the viruses and the viral receptor and co-receptor. The data suggest that viral variants with GL8-like characteristics have an early, replicative advantage and should provide the focus for future vaccine development. PMID:23372784

Willett, Brian J.; Kraase, Martin; Logan, Nicola; McMonagle, Elizabeth; Varela, Mariana; Hosie, Margaret J.

2013-01-01

305

Adaptation of Subtype A Human Immunodeficiency Virus Type 1 Envelope to Pig-Tailed Macaque Cells?  

PubMed Central

The relevance of simian/human immunodeficiency virus (SHIV) infection of macaques to HIV-1 infection in humans depends on how closely SHIVs mimic HIV-1 transmission, pathogenesis, and diversity. Circulating HIV-1 strains are predominantly subtypes C and A and overwhelmingly require CCR5 for entry, yet most SHIVs incorporate CXCR4-using subtype B envelopes (Envs). While pathogenic subtype C-based SHIVs have been constructed, the subtype A-based SHIVs (SHIV-As) constructed to date have been unable to replicate in macaque cells. To understand the barriers to SHIV-A replication in macaque cells, HIVAQ23/SIVvif was constructed by engineering a CCR5-tropic subtype A provirus to express SIV vif, which counters the macaque APOBEC3G restriction. HIVAQ23/SIVvif replicated poorly in pig-tailed macaque (Ptm) lymphocytes, but viruses were adapted to Ptm lymphocytes. Two independent mutations in gp120, G312V (V3 loop) and A204E (C2 region), were identified that increased peak virus levels by >100-fold. Introduction of G312V and A204E to multiple subtype A Envs and substitution of G312 and A204 with other residues increased entry into Ptm cells by 10- to 100-fold. G312V and A204E Env variants continued to require CCR5 for entry but were up to 50- and 200-fold more sensitive to neutralization by IgG1b12 and soluble CD4 and had a 5- to 50-fold increase in their ability to utilize Ptm CD4 compared to their wild-type counterparts. These findings identify the inefficient use of Ptm CD4 as an unappreciated restriction to subtype A HIV-1 replication in Ptm cells and reveal amino acid changes to gp120 that can overcome this barrier. PMID:21325401

Humes, Daryl; Overbaugh, Julie

2011-01-01

306

Colonization of congenitally immunodeficient mice with probiotic bacteria.  

PubMed Central

We assessed the capacity of four probiotic bacteria (Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei GG, and Bifidobacterium animalis) to colonize, infect, stimulate immune responses in, and affect the growth and survival of congenitally immunodeficient gnotobiotic beige-athymic (bg/bg-nu/nu) and beige-euthymic (bg/bg-nu/+) mice. The bacteria colonized and persisted, in pure culture, in the alimentary tracts of both mouse strains for the entire study period (12 weeks). Although all adult and neonatal beige-euthymic mice survived probiotic colonization, some infant mortality occurred in beige-athymic pups born to mothers colonized with pure cultures of L. reuteri or L. casei GG. The probiotic bacteria manifested different capacities to adhere to epithelial surfaces, disseminate to internal organs, affect the body weight of adult mice and the growth of neonatal mice, and stimulate immune responses. Although the probiotic species were innocuous for adults, these results suggest that caution and further studies to assess the safety of probiotic bacteria for immunodeficient hosts, especially neonates, are required. PMID:9234796

Wagner, R D; Warner, T; Roberts, L; Farmer, J; Balish, E

1997-01-01

307

Oral lesions: A true clinical indicator in human immunodeficiency virus  

PubMed Central

From the onset of the human immunodeficiency virus (HIV) epidemic over 20 years ago (since the appearance of the first cases of contamination by the HIV virus in the 1980s), more than 60 million people have become infected and more than 20 million people have died. An estimated 15,000 new infections occur each day, with more than 95% of these in developing countries. The distinctive characteristic in the pathogenesis of HIV/acquired immunodeficiency syndrome is that the primary target cell for HIV is immune cells bearing the CD4 marker at their surface, and the CD4 cell count and viral load have been used lately as the most important laboratory parameters to evaluate the evolution of the disease. Oral lesions are common (30–80%) in patients infected by the HIV virus and may indicate an impairment in the patient's general health status and, consequently, a poor prognosis. Oral manifestations can suggest decreased cluster-differentiated (CD4+) T cell count and increased viral load, which might also aid in diagnosis, progression, and prognosis of the disease. At the tertiary level of oral care, a dentist should be available to make definitive diagnoses of oral lesions and provide professional oral services such as prophylaxis, restorations, biopsies, and the prescription of appropriate medication. PMID:22346226

Saini, Rajiv

2011-01-01

308

Simian Immunodeficiency Virus Interactions with Macaque Dendritic Cells  

PubMed Central

This chapter summarizes advances in the following areas: (1) dendritic cell (DC)-mediated simian immunodeficiency virus (SIV) transmission, (2) role of DCs in innate and adaptive immunity against SIV, and (3) approaches to harness DC function to induce anti-SIV responses. The nonhuman primate (NHP) model of human immunodeficiency virus (HIV) infection in rhesus macaques and other Asian NHP species is highly relevant to advance the understanding of virus–host interactions critical for transmission and disease pathogenesis. HIV infection is associated with changes in frequency, phenotype, and function of the two principal subsets of DCs, myeloid DCs and plasmacytoid DCs. DC biology during pathogenic SIV infection is strikingly similar to that observed in HIV-infected patients. The NHP models provide an opportunity to dissect the requirements for DC-driven SIV infection and to understand how SIV distorts the DC system to its advantage. Furthermore, the SIV model of mucosal transmission enables the study of the earliest events of infection at the portal of entry that cannot be studied in humans, and, importantly, the involvement of DCs. Nonpathogenic infection in African NHP hosts allows investigations into the role of DCs in disease control. Understanding how DCs are altered during SIV infection is critical to the design of therapeutic and preventative strategies against HIV. PMID:22975875

Derby, Nina; Martinelli, Elena; Pugach, Pavel; Calenda, Giulia; Robbiani, Melissa

2013-01-01

309

Sarcoidosis and common variable immunodeficiency: similarities and differences.  

PubMed

Common variable immunodeficiency (CVID) is a primary immunodeficiency that is characterized by hypogammaglobulinemia and poor/absent specific antibody production. Granulomatous and lymphocytic interstitial lung disease (GLILD) is an increasingly recognized complication of CVID, occurring in 10 to 20% of patients. GLILD is characterized by non-necrotizing granuloma, lymphocytic interstitial pneumonitis and follicular bronchiolitis-histological patterns that are typically present in the same biopsy. GLILD is a multisystem disease and is frequently accompanied by diffuse adenopathy, splenomegaly, and extrapulmonary granulomatous disease most commonly in the lymph nodes, spleen, liver, and gastrointestinal tract. The presence of noncaseating granuloma in the lung along with some of the extrapulmonary features of GLILD may lead to an incorrect diagnosis of sarcoidosis. However, GLILD differs from sarcoidosis in several important ways including mode of presentation, extrapulmonary manifestations, radiographic abnormalities on high-resolution computed tomography scan of the chest, and laboratory features (serum immunoglobulins, bronchoalveolar lavage, and histopathology). The misdiagnosis of sarcoidosis in a patient with CVID and GLILD can lead to inappropriate treatment and increase the morbidity and mortality of the disorder. PMID:25007085

Verbsky, James W; Routes, John M

2014-06-01

310

Vaccine Induced Antibodies to the First Variable Loop of Human Immunodeficiency Virus Type 1 gp120, Mediate Antibody-Dependent Virus Inhibition in Macaques  

PubMed Central

The role of antibodies directed against the hyper variable envelope region V1 of human immunodeficiency virus type 1 (HIV-1), has not been thoroughly studied. We show that a vaccine able to elicit strain-specific non-neutralizing antibodies to this region of gp120 is associated with control of highly pathogenic chimeric SHIV89.6P replication in rhesus macaques. The vaccinated animal that had the highest titers of antibodies to the amino terminus portion of V1, prior to challenge, had secondary antibody responses that mediated cell killing by antibody-dependent cellular cytotoxicity (ADCC), as early as two weeks after infection and inhibited viral replication by antibody-dependent cell-mediated virus inhibition (ADCVI), by four weeks after infection. There was a significant inverse correlation between virus level and binding antibody titers to the envelope protein, (R = -0.83, p 0.015), and ADCVI (R = -0.84 p=0.044). Genotyping of plasma virus demonstrated in vivo selection of three SHIV89.6P variants with changes in potential N-linked glycosylation sites in V1. We found a significant inverse correlation between virus levels and titers of antibodies that mediated ADCVI against all the identified V1 virus variants. A significant inverse correlation was also found between neutralizing antibody titers to SHIV89.6 and virus levels (R = -0.72 p =0.0050). However, passive inoculation of purified immunoglobulin from animal M316, the macaque that best controlled virus, to a naïve macaque, resulted in a low serum neutralizing antibodies and low ADCVI activity that failed to protect from SHIV89.6P challenge. Collectively, while our data suggest that anti-envelope antibodies with neutralizing and non-neutralizing Fc?R-dependent activities may be important in the control of SHIV replication, they also demonstrate that low levels of these antibodies alone are not sufficient to protect from infection. PMID:22037204

Bialuk, Izabela; Whitney, Stephen; Andresen, Vibeke; Florese, Ruth H.; Nacsa, Janos; Cecchinato, Valentina; Valeri, Valerio W.; Heraud, Jean-Michel; Gordon, Shari; Parks, Robyn Washington; Montefiori, David C.; Venzon, David; Demberg, Thorsten; Guroff, Marjorie Robert; Landucci, Gary; Forthal, Donald N.; Franchini, Genoveffa

2011-01-01

311

UCLA1, a Synthetic Derivative of a gp120 RNA Aptamer, Inhibits Entry of Human Immunodeficiency Virus Type 1 Subtype C  

PubMed Central

Entry of human immunodeficiency virus type 1 (HIV-1) into cells is mediated by the virion surface envelope (Env) glycoproteins, making it a desirable target for antiretroviral entry inhibitors. We previously isolated a family of gp120 binding RNA aptamers and showed that they neutralized the infectivity of HIV-1. In this study, we assessed the activity of a shortened synthetic derivative of the B40 aptamer, called UCLA1, against a large panel of HIV-1 subtype C viruses. UCLA1 tightly bound to a consensus HIV-1 subtype C gp120 and neutralized isolates of the same subtype with 50% inhibitory concentrations (IC50s) in the nanomolar range. The aptamer had little toxicity in tests with cell lines and primary cells. Furthermore, it exhibited high therapeutic indices, suggesting that it may be effective at very low doses. Mapping of UCLA1 binding sites on gp120 revealed eight amino acid residues that modulated neutralization resistance. This included residues within the coreceptor binding site, at the base of the V3 loop, and in the bridging sheet within the conserved V1/V2 stem-loop of gp120. The aptamer was also shown to have synergistic effects with T20, a gp41 fusion inhibitor, and IgG1b12 (b12), an anti-CD4 binding site monoclonal antibody. These results suggest that UCLA1 may be suitable for development as a potent HIV-1 entry inhibitor. PMID:22379083

Mufhandu, Hazel T.; Gray, Elin S.; Madiga, Maphuti C.; Tumba, Nancy; Alexandre, Kabamba B.; Khoza, Thandeka; Wibmer, Constantinos Kurt; Moore, Penny L.; Morris, Lynn

2012-01-01

312

Advanced neutral-beam technology  

SciTech Connect

Extensive development will be required to achieve the 50- to 75-MW, 175- to 200-keV, 5- to 10-sec pulses of deuterium atoms envisioned for ETF and INTOR. Multi-megawatt injector systems are large (and expansive); they consist of large vacuum tanks with many square meters of cryogenic pumping panels, beam dumps capable of dissipating several megawatts of un-neutralized beam, bending magnets, electrical power systems capable of fast turnoff with low (capacity) stored energy, and, of course, the injector modules (ion sources and accelerators). The technology requirements associated with these components are described.

Berkner, K.H.

1980-09-01

313

Neutral gas dynamics in fireballs  

SciTech Connect

Fireballs are local discharge phenomena on positively biased electrodes in partially ionized plasmas. Electrons, energized at a double layer, heat neutral gas which expands. The gas pressure exceeds the plasma pressure, hence becomes important to the stability and transport in fireballs. The flow of gas moves the electrode and sensors similar to a mica pendulum. Flow speed and directions are measured. A fireball gun has been developed to partially collimate the flow of hot gas and heat objects in its path. New applications of fireballs are suggested.

Stenzel, R. L. [Department of Physics and Astronomy, University of California, Los Angeles, California 90095-1547 (United States); Ionita, C.; Schrittwieser, R. [University of Innsbruck, Department for Ion Physics and Applied Physics, A-6020 Innsbruck (Austria)

2011-06-01

314

Human immunodeficiency virus contains an epitope immunoreactive with thymosin. cap alpha. /sub 1/ and the 30-amino acid synthetic p17 group-specific antigen peptide HGP-30  

SciTech Connect

The authors have reported that an antiserum prepared against thymosin ..cap alpha../sub 1/ (which shares a region of homology with the p17 protein of the acquired immunodeficiency syndrome (AIDS)-associated human immunodeficiency virus) effectively neutralized the AIDs virus and prevented its replication in H9 cells. Using HPLC and immunoblot analysis, they have identified from a clone B, type III human T-lymphotropic virus (HTLV-IIIB) extracts a protein with a molecular weight of 17,000 that is immunoreactive with thymosin ..cap alpha../sub 1/. In contrast, no immunoreactivity was found in retroviral extracts from a number of nonhuman species including feline, bovine, simian, gibbon, and murine retroviruses. Heterologous antiserum prepared against a 30-amino acid synthetic peptide analogue (HGP-30) does not cross-react with thymosin ..cap alpha../sub 1/ but does react specifically with the p17 protein of the AIDS virus in a manner identical to that seen with an HTLV-IIIB p17-specific monoclonal antibody. The demonstration that this synthetic analogue is immunogenic and that antibodies to HGP-30 cross-react not only with synthetic peptide but also with the HTLV-IIIB p17 viral protein provides an additional, and potentially more specific, candidate for development of a synthetic peptide vaccine for AIDS. In addition, the p17 synthetic peptide (HGP-3) may prove to be useful in a diagnostic assay for the detection of AIDS virus infection in seronegative individuals.

Naylor, P.H.; Naylor, C.W.; Badamchian, M.; Wada, S.; Goldstein, A.L.; Wang, S.S.; Sun, D.K.; Thornton, A.H.; Sarin, P.S.

1987-05-01

315

Generation and characterization of monoclonal antibodies to the putative CD4-binding domain of human immunodeficiency virus type 1 gp120.  

PubMed Central

A panel of seven monoclonal antibodies against the relatively conserved CD4-binding domain on human immunodeficiency virus type 1 (HIV-1) gp120 was generated by immunizing mice with purified gp120. These monoclonal antibodies reacted specifically with gp120 in an enzyme-linked immunosorbent assay and Western blots (immunoblots). By using synthetic peptides as antigens in the immunosorbent assay, the epitopes of these seven monoclonal antibodies were mapped to amino acid residues 423 to 437 of gp120. Further studies with radioimmunoprecipitation assays showed that they cross-reacted with both gp120 and gp160 of diverse HIV-1 isolates (HTLV-IIIB, HTLV-IIIRF, HTLV-IIIAL, and HTLV-IIIWMJ). They also bound specifically to H9 cells infected with HTLV-IIIB, HTLV-IIIRF, HTLV-IIIAL, HTLV-IIIZ84, and HTLV-IIIZ34 in indirect immunofluorescence studies. In addition, they blocked effectively the binding of HIV-1 to CD4+ C8166 cells. Despite the similarity of these properties, the monoclonal antibodies differed in neutralizing activity against HTLV-IIIB, HTLV-IIIRF, and HTLV-IIIAL, as demonstrated in both syncytium-forming assays and infectivity assays. Our findings suggest that these group-specific monoclonal antibodies to the putative CD4-binding domain on gp120 are potential candidates for development of therapeutic agents against acquired immunodeficiency disease syndrome. PMID:2474670

Sun, N C; Ho, D D; Sun, C R; Liou, R S; Gordon, W; Fung, M S; Li, X L; Ting, R C; Lee, T H; Chang, N T

1989-01-01

316

Glycosylation of Simian Immunodeficiency Virus Influences Immune-Tissue Targeting during Primary Infection, Leading to Immunodeficiency or Viral Control  

PubMed Central

Glycans of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) play pivotal roles in modulating virus-target cell interactions. We have previously reported that, whereas SIVmac239 is pathogenic, its deglycosylated essentially nonpathogenic mutant (?5G) serves as a live-attenuated vaccine, although both replicate similarly during primary infection. These findings prompted us to determine whether such a polarized clinical outcome was due to differences in the immune tissues targeted by these viruses, where functionally and phenotypically different memory CD4+ T cells reside. The results showed that ?5G replicates in secondary lymphoid tissue (SLT) at 1- to 2-log-lower levels than SIVmac239, whereas SIVmac239-infected but not ?5G-infected animals deplete CXCR3+ CCR5+ transitional memory (TrM) CD4+ T cells. An early robust ?5G replication was localized to small intestinal tissue, especially the lamina propria (effector site) rather than isolated lymphoid follicles (inductive site) and was associated with the induction and depletion of CCR6+ CXCR3? CCR5+ effector memory CD4+ T cells. These results suggest that differential glycosylation of Env dictates the type of tissue-resident CD4+ T cells that are targeted, which leads to pathogenic infection of TrM-Th1 cells in SLT and nonpathogenic infection of Th17 cells in the small intestine, respectively. PMID:22718828

Sugimoto, Chie; Nakamura, Shinichiro; Hagen, Shoko I.; Tsunetsugu-Yokota, Yasuko; Villinger, Francois; Ansari, Aftab A.; Suzuki, Yasuo; Nagai, Yoshiyuki; Picker, Louis J.

2012-01-01

317

New clinical and histological patterns of acute disseminated histoplasmosis in human immunodeficiency virus-positive patients with acquired immunodeficiency syndrome.  

PubMed

Histoplasmosis has attained increasing relevance in the past 3 decades because of the appearance of the human immunodeficiency virus (HIV). In most immunocompetent persons, the infection is asymptomatic or can produce a respiratory condition with symptoms and radiological images similar to those observed in pulmonary tuberculosis; in non-HIV+ immunocompromised patients, it can cause respiratory symptoms or evolve into a disseminated infection. The same can occur in acquired immunodeficiency syndrome (AIDS) patients. We have observed a series of HIV+ patients with AIDS who presented with cutaneous histoplasmosis and in whom the clinical and histopathological features were highly unusual, including variable mucocutaneous lesions that were difficult to diagnose clinically. These patients displayed unusual, previously undescribed, histological patterns, including lichenoid pattern, nodular pseudomyxoid pattern, pyogenic granuloma-like pattern, perifollicular pattern, and superficial (S), mid (M), and deep perivascular dermatitis; and more commonly encountered patterns, such as histiocytic lobular panniculitis and focal nodular dermatitis. The novel histopathological patterns of cutaneous involvement by histoplasmosis seen in these patients resembled other common inflammatory and infectious conditions and required a high level of suspicion and the application of special stains for organisms for confirmation. These new, clinical, and histological findings do not seem to be commonly encountered in HIV- patients infected with the fungus but seem to be displayed most prominently in HIV+ patients with AIDS. PMID:22157244

Ollague Sierra, Jose E; Ollague Torres, Jose M

2013-04-01

318

Recombinant Modified Vaccinia Virus Ankara Provides Durable Protection Against Disease Caused by an Immunodeficiency Virus as well as Long Term Immunity to an Orthopoxvirus in a Non-Human Primate  

PubMed Central

Recombinant and non-recombinant modified vaccinia virus Ankara (MVA) strains are currently in clinical trials as human immunodeficiency virus-1 (HIV) and attenuated smallpox vaccines, respectively. Here we tested the ability of a recombinant MVA delivered by alternative needle-free routes (intramuscular, intradermal, or into the palatine tonsil) to protect against immunodeficiency and orthopoxvirus diseases in a non-human primate model. Rhesus macaques were immunized twice one month apart with MVA expressing 5 genes from a pathogenic simian human immunodeficiency virus (SHIV)/89.6P and challenged intrarectally 9 months later with the pathogenic SHIV/89.6P and intravenously 2.7 years later with monkeypox virus. Irrespective of the route of vaccine delivery, binding and neutralizing antibodies and CD8 responses to SHIV and orthopoxvirus proteins were induced and the monkeys were successively protected against the diseases caused by the challenge viruses in unimmunized controls as determined by viral loads and clinical signs. These non-human primate studies support the clinical testing of recombinant MVA as an HIV vaccine and further demonstrate that MVA can provide long term poxvirus immunity, essential for use as an alternative smallpox vaccine. PMID:17499326

Earl, Patricia L.; Americo, Jeffrey L.; Wyatt, Linda S.; Eller, Leigh Anne; Montefiori, David C.; Byrum, Russ; Piatak, Michael; Lifson, Jeffrey D.; Amara, Rama Rao; Robinson, Harriet L.; Huggins, John W.; Moss, Bernard

2007-01-01

319

Primary immunodeficiency in Iran: first report of the National Registry of PID in Children and Adults.  

PubMed

Epidemiological studies have shown wide geographical and racial variation in the prevalence and patterns of immunodeficiency disorders. To determine the frequency of primary immunodeficiencies (PID) in Iran, the Iranian Primary Immunodeficiency Registry (IPIDR) was organized in 1999. We extracted the patient's data, by using a uniform questionnaire from their hospital records. The diagnosis of patients was based on WHO criteria. By now, 440 patients with PID, who were observed during a period of 20 years, have been registered in our registry. Among these patients, the following frequencies were found: predominantly antibody deficiency in 45.9% of patients (n = 202), phagocytic disorders in 29.09% (n = 128), T-cell disorders in 24.31% (n = 107), and complement deficiencies in 0.68% (n = 3). Common variable immunodeficiency was the most frequent disorder (n = 98), followed by chronic granulomatous disease (n = 86), ataxia telangiectasia (n = 48), x-linked agammaglobulinemia (n = 45), selective IgA deficiency (n = 42), combined immunodeficiency (n = 15), and severe combined immunodeficiency (n = 14). This study revealed that antibody deficiencies is the most frequently diagnosed primary immunodeficiency disorder in our patients, which is similar to that observed in other registries. A comparative study shows some differences between our results and other registries. PMID:12462337

Aghamohammadi, Asghar; Moein, Mosafa; Farhoudi, Abolhasan; Pourpak, Zahra; Rezaei, Nima; Abolmaali, Kamran; Movahedi, Masoud; Gharagozlou, Mohammad; Ghazi, Bahram Mir Saeid; Mahmoudi, Maryam; Mansouri, Davoud; Arshi, Saba; Trash, Naser Javaher; Akbari, Hedayatallah; Sherkat, Roya; Hosayni, Reza Farid; Hashemzadeh, Ahmad; Mohammadzadeh, Iraj; Amin, Reza; Kashef, Sara; Alborzi, Abdalvahab; Karimi, Abdallah; Khazaei, Hosaynali

2002-11-01

320

Neutral and anionic superhalogen hydroxides  

NASA Astrophysics Data System (ADS)

The properties of superhalogen M(OH)k+1- anions and their M(OH) k+1 neutral parents (where M = Li, Na, K, Be, Mg, Ca, B, Al, Ga) were investigated at the ab initio CCSD(T)/6-311++G(3df,3pd)//MP2/6-311++G(d,p) level of theory. All the M(OH)k+1- anions and some of their M(OH) k+1 neutral parents ( k is the maximal formal valence of M) were found to be thermodynamically stable against the fragmentations (OH, OH -, O 2 or H 2O loss). The vertical electron detachment energies (VDE) of the M(OH)k+1- anions were calculated with the OVGF method and using the 6-311++G(3df,3pd) basis sets. The VDE values calculated for the anions studied exceed 4 eV in all cases, whereas the largest values of the electron binding energies were found for the Al(OH)4- (6.07 eV) and Ga(OH)4- anions (6.21 eV). Finally, formation of most of the species considered was predicted to be spontaneous due to the lack of kinetic barriers for these processes and their thermodynamic favorability.

?wierszcz, Iwona; Anusiewicz, Iwona

2011-05-01

321

Detailed Atomic Structure of Neutral and Near-Neutral Systems  

SciTech Connect

This paper highlights the issues which need to be addressed in undertaking accurate calculations of multi-electron atoms and ions, particularly at or near the neutral end of an isoelectronic sequence. We illustrate the processes through two calculations--of transitions in Cl I and Sn II--and discuss the convergence of our results as well as updating previous work. In particular, in the case of Cl I, we propose new identifications of the levels involved in certain transitions which are important in determining the abundance of chlorine in the inter-stellar medium (ISM), while in singly ionised tin, our calculations suggest a re-evaluation of the the abundance of tin in the ISM. We also confirm recent identification of Sn II lines seen in tokamak plasmas.

Oliver, Paul; Hibbert, Alan [School of Mathematics and Physics, Queen's University, Belfast BT7 1NN, Northern Ireland (United Kingdom)

2011-05-11

322

Inhibition of Virus Attachment to CD4+ Target Cells Is a Major Mechanism of T Cell Line–adapted HIV-1 Neutralization  

PubMed Central

Antibody-mediated neutralization of human immunodeficiency virus type–1 (HIV-1) is thought to function by at least two distinct mechanisms: inhibition of virus–receptor binding, and interference with events after binding, such as virus–cell membrane fusion. Here we show, by the use of a novel virus–cell binding assay, that soluble CD4 and monoclonal antibodies to all confirmed glycoprotein (gp)120 neutralizing epitopes, including the CD4 binding site and the V2 and V3 loops, inhibit the adsorption of two T cell line–adapted HIV-1 viruses to CD4+ cells. A correlation between the inhibition of virus binding and virus neutralization was observed for soluble CD4 and all anti-gp120 antibodies, indicating that this is a major mechanism of HIV neutralization. By contrast, antibodies specific for regions of gp120 other than the CD4 binding site showed little or no inhibition of either soluble gp120 binding to CD4+ cells or soluble CD4 binding to HIV-infected cells, implying that this effect is specific to the virion–cell interaction. However, inhibition of HIV-1 attachment to cells is not a universal mechanism of neutralization, since an anti-gp41 antibody did not inhibit virus–cell binding at neutralizing concentrations, implying activity after virus–cell binding. PMID:9334368

Ugolini, Sophie; Mondor, Isabelle; Parren, Paul W.H.I.; Burton, Dennis R.; Tilley, Shermaine A.; Klasse, Per Johan; Sattentau, Quentin J.

1997-01-01

323

Fatal encephalitis due to BK virus in a patient with common variable immunodeficiency: a case report.  

PubMed

Encephalitis due to BK virus is a rare condition. Here, we describe a young male patient with common variable immunodeficiency who developed fatal encephalitis due to BK virus. The patient presented initially with ocular symptoms that were followed by behavioral changes and spastic quadriparesis. Diagnosis was made by the compatible clinical findings and detection of viral DNA by polymerase chain reaction in the cerebrospinal fluid. To the best of our knowledge, this is the first report of BK virus encephalitis in a patient with common variable immunodeficiency. We suggest that BK virus should be suspected in cases of encephalitis; particularly in patients with immunodeficiency. PMID:23731846

Bakri, Faris G; Bahou, Yacoub G; Al-Sammarrai, Firas A; Hadidy, Azmy; Gharaibeh, Almutez; Zaid, Ghida K; Mahafzah, Azmi; Samara, Osama A; Ababneh, Nidaa A; Zak, Imad

2013-08-01

324

Central nervous system correlates of behavioral deficits following simian immunodeficiency virus infection  

Microsoft Academic Search

Despite the high incidence of cognitive and motor impairment in acquired immunodeficiency syndrome (AIDS) patients, the mechanisms\\u000a of AIDS-related central nervous system (CNS) pathology are not completely understood. Infection with simian immunodeficiency\\u000a virus (SIV) in macaques provides an excellent model of AIDS, including human immunodeficiency virus (HIV)-induced CNS pathology\\u000a and cognitive\\/behavioral impairment. Co-inoculation with two SIV strains, SIV\\/17E-Fr and SIV\\/DeltaB670,

Michael R. Weed; Robert D. Hienz; Joseph V. Brady; Robert J. Adams; Joseph L. Mankowski; Janice E. Clements; M. Christine Zink

2003-01-01

325

Functional characterization of the recombinant HIV-neutralizing monoclonal antibody 2F5 produced in maize seeds.  

PubMed

Monoclonal antibodies (mAbs) that neutralize human immunodeficiency virus (HIV) can be used as microbicides to help prevent the spread of HIV in human populations. As an industry standard, HIV-neutralizing mAbs are produced as recombinant proteins in mammalian cells, but the high manufacturing costs and limited capacity reduce the ability of target populations in developing countries to gain access to these potentially life-saving medicines. Plants offer a more cost-effective and deployable production platform because they can be grown inexpensively and on a large scale in the region where the products are required. Here we show that the maize-derived HIV-neutralizing mAb 2F5 is assembled correctly in planta and binds to its antigen with the same affinity as 2F5 produced in mammalian cells. Although 2F5 has been produced at high levels in non-plant platforms, the yield in maize seeds is lower than previously achieved with another HIV-neutralizing mAb, 2G12. This suggests that the intrinsic properties of the antibody (e.g. sensitivity to specific proteases) and the environment provided by the production host (e.g. the relative abundance of different proteases, potential transgene silencing) may combine to limit the accumulation of some antibodies on a case-by-case basis. PMID:22965278

Sabalza, M; Madeira, L; van Dolleweerd, C; Ma, J K; Capell, T; Christou, P

2012-11-01

326

B-Lymphocyte Dysfunction in Chronic HIV-1 Infection Does Not Prevent Cross-Clade Neutralization Breadth  

PubMed Central

Aberrant expression of regulatory receptors programmed death-1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) is linked with dysregulation and exhaustion of T lymphocytes during chronic human immunodeficiency virus type 1 (HIV-1) infection; however, less is known about whether a similar process impacts B-lymphocyte function during HIV-1 infection. We reasoned that disruption of the peripheral B cell compartment might be associated with decreased neutralizing antibody activity. Expression of markers that indicate dysregulation (BTLA and PD-1), immune activation (CD95), and proliferation (Ki-67) was evaluated in B cells from HIV-1-infected viremic and aviremic subjects and healthy subjects, in conjunction with immunoglobulin production and CD4 T cell count. Viral load and cross-clade neutralizing activity in plasma from viremic subjects were also assessed. Dysregulation of B lymphocytes was indicated by a marked disruption of peripheral B cell subsets, increased levels of PD-1 expression, and decreased levels of BTLA expression in viremic subjects compared to aviremic subjects and healthy controls. PD-1 and BTLA were correlated in a divergent fashion with immune activation, CD4 T cell count, and the total plasma IgG level, a functional correlate of B cell dysfunction. Within viremic subjects, the total IgG level correlated directly with cross-clade neutralizing activity in plasma. The findings demonstrate that even in chronically infected subjects in which B lymphocytes display multiple indications of dysfunction, antibodies that mediate cross-clade neutralization breadth continue to circulate in plasma. PMID:22623771

Boliar, Saikat; Murphy, Megan K.; Tran, T. Cameron; Carnathan, Diane G.; Armstrong, Wendy S.; Silvestri, Guido

2012-01-01

327

BEAMS3D Neutral Beam Injection Model  

SciTech Connect

With the advent of applied 3D fi elds in Tokamaks and modern high performance stellarators, a need has arisen to address non-axisymmetric effects on neutral beam heating and fueling. We report on the development of a fully 3D neutral beam injection (NBI) model, BEAMS3D, which addresses this need by coupling 3D equilibria to a guiding center code capable of modeling neutral and charged particle trajectories across the separatrix and into the plasma core. Ionization, neutralization, charge-exchange, viscous velocity reduction, and pitch angle scattering are modeled with the ADAS atomic physics database [1]. Benchmark calculations are presented to validate the collisionless particle orbits, neutral beam injection model, frictional drag, and pitch angle scattering effects. A calculation of neutral beam heating in the NCSX device is performed, highlighting the capability of the code to handle 3D magnetic fields.

Lazerson, Samuel

2014-04-14

328

Toward Effective HIV Vaccination INDUCTION OF BINARY EPITOPE REACTIVE ANTIBODIES WITH BROAD HIV NEUTRALIZING ACTIVITY  

SciTech Connect

We describe murine monoclonal antibodies (mAbs) raised by immunization with an electrophilic gp120 analog (E-gp120) expressing the rare ability to neutralize genetically heterologous human immunodeficiency virus (HIV) strains. Unlike gp120, E-gp120 formed covalent oligomers. The reactivity of gp120 and E-gp120 with mAbs to reference neutralizing epitopes was markedly different, indicating their divergent structures. Epitope mapping with synthetic peptides and electrophilic peptide analogs indicated binary recognition of two distinct gp120 regions by anti-E-gp120 mAbs, the 421-433 and 288-306 peptide regions. Univalent Fab and single chain Fv fragments expressed the ability to recognize both peptides. X-ray crystallography of an anti-E-gp120 Fab fragment revealed two neighboring cavities, the typical antigen-binding cavity formed by the complementarity determining regions (CDRs) and another cavity dominated by antibody heavy chain variable (VH) domain framework (FR) residues. Substitution of the FR cavity VH Lys-19 residue by an Ala residue resulted in attenuated binding of the 421-433 region peptide probe. The CDRs and VH FR replacement/silent mutation ratios exceeded the ratio for a random mutation process, suggesting adaptive development of both putative binding sites. All mAbs studied were derived from VH1 family genes, suggesting biased recruitment of the V gene germ line repertoire by E-gp120. The conserved 421-433 region of gp120 is essential for HIV binding to host CD4 receptors. This region is recognized weakly by the FR of antibodies produced without exposure to HIV, but it usually fails to induce adaptive synthesis of neutralizing antibodies. We present models accounting for improved CD4-binding site recognition and broad HIV neutralizing activity of the mAbs, long sought goals in HIV vaccine development.

Nishiyama, Yasuhiro; Planque, Stephanie; Mitsuda, Yukie; Nitti, Giovanni; Taguchi, Hiroaki; Jin, Lei; Symersky, Jindrich; Boivin, Stephane; Sienczyk, Marcin; Salas, Maria; Hanson, Carl V.; Paul, Sudhir; (Texas-MED); (Viral Rickettsial)

2009-11-23

329

FELINE IMMUNODEFICIENCY VIRUS (FIV) IN WILD PALLAS’ CATS  

PubMed Central

Feline immunodeficiency virus (FIV), a feline lentivirus related to HIV, causes immune dysfunction in domestic and wild cats. The Pallas’ cat is the only species from Asia known to harbor a species-specific strain of FIV designated FIVOma in natural populations. Here, a 25% seroprevalence of FIV is reported from 28 wild Mongolian Pallas’ cats sampled from 2000-2008. Phylogenetic analysis of proviral RT-Pol from eight FIVOma isolates from Mongolia, Russia, China and Kazakhstan reveals a unique monophyletic lineage of the virus within the Pallas’ cat population, most closely related to the African cheetah and leopard FIV strains. Histopathological examination of lymph node and spleen from infected and uninfected Pallas’ cats suggests that FIVOma causes immune depletion in its’ native host. PMID:19926144

Brown, Meredith A.; Munkhtsog, Bariushaa; Troyer, Jennifer L.; Ross, Steve; Sellers, Rani; Fine, Amanda E.; Swanson, William F.; Roelke, Melody E.; O’Brien1, Stephen J.

2009-01-01

330

Newborn screening for severe combined immunodeficiency: an opportunity for intervention.  

PubMed

Severe combined immunodeficiency (SCID) is a potentially fatal disorder characterized by defective T- and B-lymphocyte function. We describe a 34-week female twin who had developed feeding intolerance, perioral cyanosis, abdominal distension and neutropenia at 1 month of age. Despite several evaluations including an 'inconclusive' newborn screening result for SCID, the presence of profound lymphopenia was unappreciated. Eventually a diagnosis of SCID in association with adenosine deaminase deficiency was made. This case serves to emphasize the importance of newborn screening for SCID in the context of careful evaluation of clinical and laboratory findings that may be overlooked and result in a delay in the diagnosis of a potentially life-threatening condition. PMID:23897312

Buchbinder, D; Puthenveetil, G; Soni, A; Hsieh, L; Nugent, D; Church, J A

2013-08-01

331

Glanzmann Thrombasthenia Associated with Human Immunodeficiency Virus-Positive Patient  

PubMed Central

Glanzmann's thrombasthenia (GT) is an autosomal recessive inherited platelet function defect characterized by normal platelet count, prolonged bleeding time and abnormal clot retraction. This disease typically presents in infancy or early childhood and has proven to have very good prognosis. In this case study, a 22-year-old GT patient who also developed human immunodeficiency virus (HIV) infection after sometime is reported. The patient showed oral manifestations of gingival hyperplasia and petechial lesions. Unfortunately the detection of both thrombasthenia and HIV were done at considerably late stages which contributed to a poor prognosis. The patient died of cardiopulmonary arrest secondary to HIV, thrombasthenia and thrombocytopenia. The importance of early detection, supportive care and communication between the general and oral physician in management of the GT is also discussed. PMID:24829739

Manne, Rakesh Kumar; Natarajan, Kannan; Patil, Rajendra; Prathi, Venkata Sarath; Beeraka, Swapna Sridevi; Kolaparthi, Venkata Suneel Kumar

2014-01-01

332

Renal transplantation in human immunodeficiency virus (HIV)-positive children.  

PubMed

Renal transplantation is being performed in adult human immunodeficiency virus (HIV)-positive patients and increasingly in paediatric patients as well. A multidisciplinary team involving an infectious disease professional is required to assist with HIV viral-load monitoring and in choosing the most appropriate highly active antiretroviral therapy (HAART). Drug interactions complicate immunosuppressant therapy and require careful management. The acute rejection rates appear to be similar in adults to those in noninfective transplant recipients. Induction with basiliximab and calcineurin-based immunosuppression appears to be safe and effective in these recipients. Prophylaxis is advised for a variety of infections and may need life-long administration, especially in children. Organ shortage remains a significant problem, and kidneys from deceased HIV-positive donors have been used successfully in a small study population. Overall, with careful planning and close follow-up, successful renal transplantation for paediatric HIV-infected recipients is possible. PMID:24691821

McCulloch, Mignon I; Kala, Udai K

2015-04-01

333

Innate Immune Evasion Strategies by Human Immunodeficiency Virus Type 1  

PubMed Central

Host immune components play both beneficial and pathogenic roles in human immunodeficiency virus type 1 (HIV-1) infection. During the initial stage of viral infection, a complex network of innate immune factors are activated. For instance, the immune cells express a number of inflammatory proteins including cytokines, chemokines, and antiviral restriction factors. These factors, specifically, interferons (IFNs) play a crucial role in antiviral defense system by modulating the downstream signaling events, by inducing maturation of dendritic cells (DCs), and by activation of macrophages, natural killer (NK) cells, and B and T cells. However, HIV-1 has evolved to utilize a number of strategies to overcome the antiviral effects of the host innate immune system. This review discusses the pathways and strategies utilized by HIV-1 to establish latent and persistent infection by defeating host's innate defense system. PMID:24052891

Guha, Debjani; Ayyavoo, Velpandi

2013-01-01

334

Human immunodeficiency virus type 1 inhibitory activity of Mentha longifolia.  

PubMed

Extracts from a new chemotype of Mentha longifolia, a mint species that grows spontaneously and widely in the Moroccan mountains, were tested against human immunodeficiency virus type 1 (HIV-1). We observed that non-toxic concentrations (10 microg/mL) of extracts from this plant, in particular methanol (Ext-1) and ethyl acetate (Ext-3) extracts, significantly inhibit (p < 0.01) HIV-1BaL infection by about 40% and 55%, respectively. In addition, only Ext-3 shows significant (p < 0.008) inhibitory activity (50% inhibition) against HIV-1 reverse transcriptase. It is noteworthy that chemical analysis of these extracts suggests that flavonoids, mainly flavones of M. longifolia, may be the major inhibitors of HIV infection. In conclusion, these in vitro data suggest that components of M. longifolia may represent potential anti-HIV agents; the identification of such components is in progress. PMID:15058498

Amzazi, Saaïd; Ghoulami, Saaïd; Bakri, Youssef; Il Idrissi, Abdelkader; Fkih-Tétouani, Souad; Benjouad, Abdelaziz

2003-01-01

335

Hepatitis C, human immunodeficiency virus and metabolic syndrome: interactions.  

PubMed

Significant concerns have been raised about the metabolic effects of antiretroviral medication, including the classic triad of dyslipidaemia, insulin resistance (IR) and characteristic alterations in fat distribution (lipoatrophy and lipohypertrophy). Co-infection with hepatitis C appears to exacerbate IR, reduce serum lipids and induce prothrombotic changes in the treated human immunodeficiency virus patient. The effects of co-infection are complex. While combination antiretroviral therapy has been shown to be associated with an increased risk of cardiovascular events through promotion of dyslipidaemia, IR and fat redistribution, co-infection exacerbates IR while reducing serum lipids. Co-infection also promotes a prothrombotic state characterized by endothelial dysfunction and platelet activation, which may enhance risk for cardiovascular disease. Consideration must be given to selection of appropriate treatment regimens and timing of therapy in co-infected patients to minimize metabolic derangements and, ultimately, reduce cardiovascular risk. PMID:19187071

Kotler, Donald P

2009-03-01

336

[Factors involved in resistance to human immunodeficiency virus infection].  

PubMed

Repeated exposure to human immunodeficiency virus (HIV) is not always associated with infection and a subset of individuals remains persistently as HIV-seronegative despite multiple episodes of HIV exposure. These individuals are called HIV-exposed seronegatives (ESN). Several genetic and immunological factors have been involved in this resistance to HIV acquisition. Genetic factors have been linked to genes encoding chemokine receptors and their natural ligands as well as genes of the major histocompatibility complex. Immunological factors include both innate and adaptive immunity. The study of ESN provides a unique opportunity to unveil the mechanisms of natural protection against viral infection. Their better understanding may lead to novel preventive and immune-therapeutic approaches, including vaccines. PMID:21382628

Restrepo, Clara; Rallón, Norma Ibón; Benito, José Miguel

2011-11-19

337

Overview of Microbicides for the prevention of human immunodeficiency virus  

PubMed Central

Human immunodeficiency virus (HIV) prevention tools that women can use and control are urgently needed. Microbicides are chemical products applied to the vagina or rectum to prevent the sexual transmission of HIV. Four classes of candidate microbicides have been tested to date: those that (1) enhance the natural defences in the vagina to inactivate HIV; (2) inactivate HIV in the vagina; (3) prevent HIV from attaching to, and fusing with, the host cells; and (4) prevent HIV from replicating in genital tract host cells. Despite numerous disappointing efficacy trial results over the past 20 years, substantial progress is now being made in microbicide development after the release of the CAPRISA 004 trial, which provided proof-of-concept that topical antiretroviral microbicides can prevent sexual transmission of HIV and herpes simplex type-2 infection. Microbicides, which fill an important gap for women-controlled prevention methods, have the potential to alter the course of the HIV pandemic. PMID:22386823

Abdool Karim, Salim S.; Baxter, Cheryl

2012-01-01

338

Utility of next generation sequencing in clinical primary immunodeficiencies.  

PubMed

Primary immunodeficiencies (PIDs) are a group of genetically heterogeneous disorders that present with very similar symptoms, complicating definitive diagnosis. More than 240 genes have hitherto been associated with PIDs, of which more than 30 have been identified in the last 3 years. Next generation sequencing (NGS) of genomes or exomes of informative families has played a central role in the discovery of novel PID genes. Furthermore, NGS has the potential to transform clinical molecular testing for established PIDs, allowing all PID differential diagnoses to be tested at once, leading to increased diagnostic yield, while decreasing both the time and cost of obtaining a molecular diagnosis. Given that treatment of PID varies by disease gene, early achievement of a molecular diagnosis is likely to enhance treatment decisions and improve patient outcomes. PMID:25149170

Raje, Nikita; Soden, Sarah; Swanson, Douglas; Ciaccio, Christina E; Kingsmore, Stephen F; Dinwiddie, Darrell L

2014-10-01

339

Nef proteins from simian immunodeficiency viruses are tetherin antagonists.  

PubMed

The tetherin/BST2/CD317 protein blocks the release of HIV-1 and other enveloped viruses by inducing tethering of nascent particles to infected cell surfaces. The HIV-1 Vpu protein antagonizes the antiviral activity of human but not monkey tetherins and many simian immunodeficiency viruses (SIVs) do not encode Vpu. Here, we show that the apparently "missing" antitetherin activity in SIVs has been acquired by several SIV Nef proteins. Specifically, SIV(MAC)/SIV(SMM), SIV(AGM), and SIV(BLU) Nef proteins can suppress tetherin activity. Notably, tetherin antagonism by SIV Nef proteins is species specific, is genetically separable from other Nef activities, and is most evident with simian rather than human tetherin proteins. Accordingly, a critical determinant of sensitivity to SIV(MAC) Nef in the tetherin cytoplasmic tail is variable in nonhuman primate tetherins and deleted in human tetherin, likely due to selective pressures imposed by viral antagonists, perhaps including Nef proteins. PMID:19501037

Zhang, Fengwen; Wilson, Sam J; Landford, Wilmina C; Virgen, Beatriz; Gregory, Devon; Johnson, Marc C; Munch, Jan; Kirchhoff, Frank; Bieniasz, Paul D; Hatziioannou, Theodora

2009-07-23

340

Feline immunodeficiency virus (FIV) in wild Pallas' cats.  

PubMed

Feline immunodeficiency virus (FIV), a feline lentivirus related to HIV, causes immune dysfunction in domestic and wild cats. The Pallas' cat is the only species from Asia known to harbor a species-specific strain of FIV designated FIV(Oma) in natural populations. Here, a 25% seroprevalence of FIV is reported from 28 wild Mongolian Pallas' cats sampled from 2000 to 2008. Phylogenetic analysis of proviral RT-Pol from eight FIV(Oma) isolates from Mongolia, Russia, China and Kazakhstan reveals a unique monophyletic lineage of the virus within the Pallas' cat population, most closely related to the African cheetah and leopard FIV strains. Histopathological examination of lymph node and spleen from infected and uninfected Pallas' cats suggests that FIV(Oma) causes immune depletion in its' native host. PMID:19926144

Brown, Meredith A; Munkhtsog, Bariushaa; Troyer, Jennifer L; Ross, Steve; Sellers, Rani; Fine, Amanda E; Swanson, William F; Roelke, Melody E; O'Brien, Stephen J

2010-03-15

341

Pyoderma gangrenosum in a patient with common variable primary immunodeficiency  

PubMed Central

Pyoderma gangrenosum is a rare inflammatory skin condition that is associated with systemic inflammatory diseases. It is characterised by the presence of well-secluded, painful ulcerations, often located on the lower limbs. Similarly as in the case of acne inversa, patients’ markers of the inflammatory process are elevated; including OB, C-reactive protein and leukocytosis. The aetiology takes into account an over-reactive inflammatory response to various factors (presence of the so-called pathergy symptom). Common variable primary immunodeficiency (CVID) is a disease that is rather often recognized and affects about 1/10,000-100,000 individuals. It is a heterogeneous group of disorders of combined B-and T-cell dysfunction. The case is described of a 22-year-old man with pyoderma gangrenosum that coexisted with CVID. PMID:24278072

Brzezi?ska-Wcis?o, Ligia

2013-01-01

342

Non-M Variants of Human Immunodeficiency Virus Type 1  

PubMed Central

SUMMARY The AIDS pandemic that started in the early 1980s is due to human immunodeficiency virus type 1 (HIV-1) group M (HIV-M), but apart from this major group, many divergent variants have been described (HIV-1 groups N, O, and P and HIV-2). The four HIV-1 groups arose from independent cross-species transmission of the simian immunodeficiency viruses (SIVs) SIVcpz, infecting chimpanzees, and SIVgor, infecting gorillas. This, together with human adaptation, accounts for their genomic, phylogenetic, and virological specificities. Nevertheless, the natural course of non-M HIV infection seems similar to that of HIV-M. The virological monitoring of infected patients is now possible with commercial kits, but their therapeutic management remains complex. All non-M variants were principally described for patients linked to Cameroon, where HIV-O accounts for 1% of all HIV infections; only 15 cases of HIV-N infection and 2 HIV-P infections have been reported. Despite improvements in our knowledge, many fascinating questions remain concerning the origin, genetic evolution, and slow spread of these variants. Other variants may already exist or may arise in the future, calling for close surveillance. This review provides a comprehensive, up-to-date summary of the current knowledge on these pathogens, including the historical background of their discovery; the latest advances in the comprehension of their origin and spread; and clinical, therapeutic, and laboratory aspects that may be useful for the management and the treatment of patients infected with these divergent viruses. PMID:23824367

Mourez, Thomas; Simon, François

2013-01-01

343

Structural basis for differential neutralization of ebolaviruses.  

PubMed

There are five antigenically distinct ebolaviruses that cause hemorrhagic fever in humans or non-human primates (Ebola virus, Sudan virus, Reston virus, Taï Forest virus, and Bundibugyo virus). The small handful of antibodies known to neutralize the ebolaviruses bind to the surface glycoprotein termed GP?,?. Curiously, some antibodies against them are known to neutralize in vitro but not protect in vivo, whereas other antibodies are known to protect animal models in vivo, but not neutralize in vitro. A detailed understanding of what constitutes a neutralizing and/or protective antibody response is critical for development of novel therapeutic strategies. Here, we show that paradoxically, a lower affinity antibody with restricted access to its epitope confers better neutralization than a higher affinity antibody against a similar epitope, suggesting that either subtle differences in epitope, or different characteristics of the GP?,? molecules themselves, confer differential neutralization susceptibility. Here, we also report the crystal structure of trimeric, prefusion GP?,? from the original 1976 Boniface variant of Sudan virus complexed with 16F6, the first antibody known to neutralize Sudan virus, and compare the structure to that of Sudan virus, variant Gulu. We discuss new structural details of the GP?-GP? clamp, thermal motion of various regions in GP?,? across the two viruses visualized, details of differential interaction of the crystallized neutralizing antibodies, and their relevance for virus neutralization. PMID:22590681

Bale, Shridhar; Dias, Joao M; Fusco, Marnie L; Hashiguchi, Takao; Wong, Anthony C; Liu, Tong; Keuhne, Ana I; Li, Sheng; Woods, Virgil L; Chandran, Kartik; Dye, John M; Saphire, Erica Ollmann

2012-04-01

344

Structural Basis for Differential Neutralization of Ebolaviruses  

PubMed Central

There are five antigenically distinct ebolaviruses that cause hemorrhagic fever in humans or non-human primates (Ebola virus, Sudan virus, Reston virus, Taï Forest virus, and Bundibugyo virus). The small handful of antibodies known to neutralize the ebolaviruses bind to the surface glycoprotein termed GP1,2. Curiously, some antibodies against them are known to neutralize in vitro but not protect in vivo, whereas other antibodies are known to protect animal models in vivo, but not neutralize in vitro. A detailed understanding of what constitutes a neutralizing and/or protective antibody response is critical for development of novel therapeutic strategies. Here, we show that paradoxically, a lower affinity antibody with restricted access to its epitope confers better neutralization than a higher affinity antibody against a similar epitope, suggesting that either subtle differences in epitope, or different characteristics of the GP1,2 molecules themselves, confer differential neutralization susceptibility. Here, we also report the crystal structure of trimeric, prefusion GP1,2 from the original 1976 Boniface variant of Sudan virus complexed with 16F6, the first antibody known to neutralize Sudan virus, and compare the structure to that of Sudan virus, variant Gulu. We discuss new structural details of the GP1-GP2 clamp, thermal motion of various regions in GP1,2 across the two viruses visualized, details of differential interaction of the crystallized neutralizing antibodies, and their relevance for virus neutralization. PMID:22590681

Bale, Shridhar; Dias, Joao M.; Fusco, Marnie L.; Hashiguchi, Takao; Wong, Anthony C.; Liu, Tong; Keuhne, Ana I.; Li, Sheng; Woods, Virgil L.; Chandran, Kartik; Dye, John M.; Saphire, Erica Ollmann

2012-01-01

345

EFFECTS OF LEAKAGE NEUTRAL PARTICLES ON SHOCKS  

SciTech Connect

In this paper, we investigate effects of neutral particles on shocks propagating into the partially ionized medium. We find that for 120 km s{sup -1} < u {sub sh} < 3000 km s{sup -1} (u {sub sh} is the shock velocity), about 10% of upstream neutral particles leak into the upstream region from the downstream region. Moreover, we investigate how the leakage neutral particles affect the upstream structure of the shock and particle accelerations. Using four-fluid approximations (upstream ions, upstream neutral particles, leakage neutral particles, and pickup ions), we provide analytical solutions of the precursor structure due to leakage neutral particles. It is shown that the upstream flow is decelerated in the precursor region and the shock compression ratio becomes smaller than without leakage neutral particles, but the total compression ratio does not change. Even if leakage of neutral particles is small (a few percent of total upstream particles), this smaller compression ratio of the shock can explain steep gamma-ray spectra from young supernova remnants. Furthermore, leakage neutral particles could amplify the magnetic field and heat the upstream region.

Ohira, Yutaka, E-mail: ohira@phys.aoyama.ac.jp [Department of Physics and Mathematics, Aoyama Gakuin University, 5-10-1 Fuchinobe, Sagamihara 252-5258 (Japan)

2012-10-20

346

Increased infectivity in human cells and resistance to antibody-mediated neutralization by truncation of the SIV gp41 cytoplasmic tail.  

PubMed

The role of antibodies in protecting the host from human immunodeficiency virus type 1 (HIV-1) infection is of considerable interest, particularly because the RV144 trial results suggest that antibodies contribute to protection. Although infection of non-human primates with simian immunodeficiency virus (SIV) is commonly used as an animal model of HIV-1 infection, the viral epitopes that elicit potent and broad neutralizing antibodies to SIV have not been identified. We isolated a monoclonal antibody (MAb) B404 that potently and broadly neutralizes various SIV strains. B404 targets a conformational epitope comprising the V3 and V4 loops of Env that intensely exposed when Env binds CD4. B404-resistant variants were obtained by passaging viruses in the presence of increasing concentration of B404 in PM1/CCR5 cells. Genetic analysis revealed that the Q733stop mutation, which truncates the cytoplasmic tail of gp41, was the first major substitution in Env during passage. The maximal inhibition by B404 and other MAbs were significantly decreased against a recombinant virus with a gp41 truncation compared with the parental SIVmac316. This indicates that the gp41 truncation was associated with resistance to antibody-mediated neutralization. The infectivities of the recombinant virus with the gp41 truncation were 7,900-, 1,000-, and 140-fold higher than those of SIVmac316 in PM1, PM1/CCR5, and TZM-bl cells, respectively. Immunoblotting analysis revealed that the gp41 truncation enhanced the incorporation of Env into virions. The effect of the gp41 truncation on infectivity was not obvious in the HSC-F macaque cell line, although the resistance of viruses harboring the gp41 truncation to neutralization was maintained. These results suggest that viruses with a truncated gp41 cytoplasmic tail were selected by increased infectivity in human cells and by acquiring resistance to neutralizing antibody. PMID:23717307

Kuwata, Takeo; Kaori, Takaki; Enomoto, Ikumi; Yoshimura, Kazuhisa; Matsushita, Shuzo

2013-01-01

347

75 FR 51273 - Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately Affected Populations  

Federal Register 2010, 2011, 2012, 2013

...Human Immunodeficiency Virus (HIV) Prevention and Public Health Fund Activities...follows. Part A--HIV Screening and HIV Counseling, Testing, and Referral...costs.) Both Part A (HIV Screening and HIV Counseling, Testing, and...

2010-08-19

348

Adjunctive Passive Immunotherapy in Human Immunodeficiency Virus Type 1-Infected Individuals Treated with Antiviral Therapy during Acute and Early Infection? †  

PubMed Central

Three neutralizing monoclonal antibodies (MAbs), 2G12, 2F5, and 4E10, with activity in vitro and in vivo were administered in an open-label, nonrandomized, proof-of-concept study to attempt to prevent viral rebound after interruption of antiretroviral therapy (ART). Ten human immunodeficiency virus type 1-infected individuals identified and treated with ART during acute and early infection were enrolled. The first six patients were administered 1.0 g of each of the three MAbs per infusion. The remaining four patients received 2G12 at 1.0 g/infusion and 2.0 g/infusion of 2F5 and 4E10. The MAbs were well tolerated. Grade I post-partial thromboplastin time prolongations were noted. Viral rebound was observed in 8/10 subjects (28 to 73 days post-ART interruption), and 2/10 subjects remained aviremic over the course of the study. In seven of eight subjects with viral rebound, clear resistance to 2G12 emerged, whereas reductions in the susceptibilities of plasma-derived recombinant viruses to 2F5 and 4E10 were neither sustained nor consistently measured. Viral rebound was associated with a preferential depletion of CD4+ T cells within the gastrointestinal tract. Though safe, the use of MAbs generally delayed, but did not prevent, virologic rebound. Consideration should be given to further pilot studies with alternative combinations of MAbs and perhaps additional novel treatment modalities. PMID:17686878

Mehandru, Saurabh; Vcelar, Brigitta; Wrin, Terri; Stiegler, Gabriela; Joos, Beda; Mohri, Hiroshi; Boden, Daniel; Galovich, Justin; Tenner-Racz, Klara; Racz, Paul; Carrington, Mary; Petropoulos, Christos; Katinger, Hermann; Markowitz, Martin

2007-01-01

349

Prevention of immunodeficiency virus induced CD4+ T-cell depletion by prior infection with a non-pathogenic virus  

SciTech Connect

Immune dysregulation initiated by a profound loss of CD4+ T-cells is fundamental to HIV-induced pathogenesis. Infection of domestic cats with a non-pathogenic lentivirus prevalent in the puma (puma lentivirus, PLV or FIV{sub PCO}) prevented peripheral blood CD4+ T-cell depletion caused by subsequent virulent FIV infection. Maintenance of this critical population was not associated with a significant decrease in FIV viremia, lending support to the hypothesis that direct viral cytopathic effect is not the primary cause of immunodeficiency. Although this approach was analogous to immunization with a modified live vaccine, correlates of immunity such as a serum-neutralizing antibody or virus-specific T-cell proliferative response were not found in protected animals. Differences in cytokine transcription profile, most notably in interferon gamma, were observed between the protected and unprotected groups. These data provide support for the importance of non-adaptive enhancement of the immune response in the prevention of CD4+ T-cell loss.

TerWee, Julie A.; Carlson, Jennifer K.; Sprague, Wendy S.; Sondgeroth, Kerry S.; Shropshire, Sarah B.; Troyer, Jennifer L. [Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado (United States); VandeWoude, Sue [Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado (United States)], E-mail: suev@lamar.colostate.edu

2008-07-20

350

Evolution of Circulating Wild Poliovirus and of Vaccine-Derived Poliovirus in an Immunodeficient Patient: a Unifying Model  

PubMed Central

We determined nucleotide sequences of the VP1 and 2AB genes and portions of the 2C and 3D genes of two evolving poliovirus lineages: circulating wild viruses of T geotype and Sabin vaccine-derived isolates from an immunodeficient patient. Different regions of the viral RNA were found to evolve nonsynchronously, and the rate of evolution of the 2AB region in the vaccine-derived population was not constant throughout its history. Synonymous replacements occurred not completely randomly, suggesting the need for conservation of certain rare codons (possibly to control translation elongation) and the existence of unidentified constraints in the viral RNA structure. Nevertheless the major contribution to the evolution of the two lineages came from linear accumulation of synonymous substitutions. Therefore, in agreement with current theories of viral evolution, we suggest that the majority of the mutations in both lineages were fixed as a result of successive sampling, from the heterogeneous populations, of random portions containing predominantly neutral and possibly adverse mutations. As a result of such a mode of evolution, the virus fitness may be maintained at a more or less constant level or may decrease unless more-fit variants are stochastically generated. The proposed unifying model of natural poliovirus evolution has important implications for the epidemiology of poliomyelitis. PMID:10906191

Gavrilin, Gene V.; Cherkasova, Elena A.; Lipskaya, Galina Y.; Kew, Olen M.; Agol, Vadim I.

2000-01-01

351

Fine Definition of the CXCR4-Binding Region on the V3 Loop of Feline Immunodeficiency Virus Surface Glycoprotein  

PubMed Central

The chemokine receptor CXCR4 is shared by primary and laboratory-adapted strains of feline immunodeficiency virus (FIV) for viral entry. Our previous studies implicated a contiguous nine-amino-acid region of the V3 loop of the FIV envelope surface as important in CXCR4 binding and virus entry. The binding is specific for CXCR4 since it can be inhibited by AMD3100, a selective CXCR4 inhibitor. Additional site-directed mutagenesis was used to further reveal the key residues. Binding studies indicated that basic residues R395, K397, R399 as well as N398 are critical for CXCR4 binding. The effect of other amino acid residues on receptor binding depends on the type of amino acid residue substituted. The binding study results were confirmed on human CXCR4-expressing SupT1 cells and correlated with entry efficiency using a virus entry assay. Amino acid residues critical for CXCR4 are not critical for interactions with the primary binding receptor CD134, which has an equivalent role as CD4 for HIV-1 binding. The ELISA results show that W394 and W400 are crucial for the recognition by neutralizing anti-V3 antibodies. Since certain strains of HIV-1 also use CXCR4 as the entry receptor, the findings make the feline model attractive for development of broad-based entry antagonists and for study of the molecular mechanism of receptor/virus interactions. PMID:20502526

Hu, Qiong-Ying; Fink, Elizabeth; Hong, Yang; Wang, Cathy; Grant, Chris K.; Elder, John H.

2010-01-01

352

Ex-vivo assays of dendritic cell activation and cytokine profiles as predictors of in vivo effects in an anti-human CD40 monoclonal antibody ChiLob 7/4 Phase I trial  

PubMed Central

Immunostimulatory antibodies entering the clinic create challenges not only in terms of pharmacodynamics for monitoring anticipated mechanism but also in pre-determining cytotoxicity. We demonstrate the use of ex-vivo whole blood samples to predict the activation requirements, cytokine signature and adverse events of an anti-human-CD40 chimeric IgG1 antibody, ChiLob7/4. Assessments were initially undertaken on human myeloid (mDC1) and plasmacytoid (pDC) dendritic cells where an absolute need for cross-linking was demonstrated through the up-regulation of activation markers CD83 and CCR7. Subsequent cytokine secretion evaluations of ex-vivo whole blood showed the cross-linked antibody induced increases in MIP1?, IL-8, IL-12, TNF?, and IL-6. This cytokine signature compared favorably to the TLR ligand LPS, where levels of TNF? and IL-6 were significantly higher, suggesting a less intense pro-inflammatory response and possible modified cytokine-release-syndrome when used in human trials. Following first-in-human use of this agent within a dose escalation study, in-vivo evaluations of DC activation and secreted cytokines closely matched the predetermined immunomonitoring endpoints. Patients showed a comparable pattern of MIP1?, IL-8, and IL-12 secretion but no TNF?, and IL-6 was identified. Mild symptoms relating to a cytokine-release-syndrome were seen at an equivalent dosage to that observed for DC activation and cytokine release. In summary, ChiLob7/4 induces a distinctive pattern of DC activation and cytokine secretion in ex-vivo assays that can be predictive of in-vivo responses. Such pre-clinical approaches to monoclonal antibody evaluation may inform both the starting dosages and the anticipated cytokine release events that could occur, providing a valuable adjunct for future first-in-human assessments of immunostimulatory antibodies. PMID:24778319

Chowdhury, F.; Johnson, P. W.; Glennie, M.J.; Williams, A. P.

2013-01-01

353

Charged-particle optics for neutral particles  

NASA Astrophysics Data System (ADS)

Electromagnetic manipulation of charged and of neutral particles generally requires very different field geometries due to the orthogonality between charge monopoles and neutral dipoles. This has led to a natural separation between the fields of charged- and neutral-particle optics. We show however that the additional rotational degree of freedom of neutral dipoles can lead to an equivalence between the forces on charge monopoles and neutral dipoles under the action of axially/cylindrically symmetric fields. In this way, we show how to extend and exploit the large set of already developed cylindrically symmetric charged particle optics for use on neutral dipolar particles. The result is a large new class of focusing optics for all neutral particles of non-zero magnetic dipole moments, including neutrons, neutral atoms, and neutral molecules. Apart from the increased variety of focusing optics, such systems possess many advantages over previously existing magnetic neutral particles lenses, including lens strength, accessible aperture area, accuracy, robustness, and much improved ease of fabrication and use. We construct a neutral Rubidium atomic beam with which we experimentally demonstrate three such new focusing lenses, including annular permanent magnetic rings, a "magnetostatic aperture" lens, and a magnetizable lenslet array. As an extension of this result we propose a dynamically variable superconducting lens system for neutrons that is able to focus neutrons with a wide range of energies (from ultra-cold through to thermal). The proposed neutron system compares favorably with existing neutron optics, being in particular substantially more powerful than similar existing refraction-based neutron lenses.

Zabow, Gary

354

Gamma/Delta T-Cell Functional Responses Differ after Pathogenic Human Immunodeficiency Virus and Nonpathogenic Simian Immunodeficiency Virus Infections?  

PubMed Central

The objective of this study was to functionally assess gamma/delta (??) T cells following pathogenic human immunodeficiency virus (HIV) infection of humans and nonpathogenic simian immunodeficiency virus (SIV) infection of sooty mangabeys. ?? T cells were obtained from peripheral blood samples from patients and sooty mangabeys that exhibited either a CD4-healthy (>200 CD4+ T cells/?l blood) or CD4-low (<200 CD4 cells/?l blood) phenotype. Cytokine flow cytometry was utilized to assess production of Th1 cytokines tumor necrosis factor alpha and gamma interferon following ex vivo stimulation with either phorbol myristate acetate/ionomycin or the V?2 ?? T-cell receptor agonist isopentenyl pyrophosphate. Sooty mangabeys were observed to have higher percentages of ?? T cells in their peripheral blood than humans did. Following stimulation, ?? T cells from SIV-positive (SIV+) mangabeys maintained or increased their ability to express the Th1 cytokines regardless of CD4+ T-cell levels. In contrast, HIV-positive (HIV+) patients exhibited a decreased percentage of ?? T cells expressing Th1 cytokines following stimulation. This dysfunction is primarily within the V?2+ ?? T-cell subset which incurred both a decreased overall level in the blood and a reduced Th1 cytokine production. Patients treated with highly active antiretroviral therapy exhibited a partial restoration in their ?? T-cell Th1 cytokine response that was intermediate between the responses of the uninfected and HIV+ patients. The SIV+ sooty mangabey natural hosts, which do not proceed to clinical AIDS, provide evidence that ?? T-cell dysfunction occurs in HIV+ patients and may contribute to HIV disease progression. PMID:18045946

Kosub, David A.; Lehrman, Ginger; Milush, Jeffrey M.; Zhou, Dejiang; Chacko, Elizabeth; Leone, Amanda; Gordon, Shari; Silvestri, Guido; Else, James G.; Keiser, Philip; Jain, Mamta K.; Sodora, Donald L.

2008-01-01

355

Human immunodeficiency virus/acquired immunodeficiency syndrome knowledge among high school students in K?r?kkale province of Turkey  

PubMed Central

Background: The purpose of the present study was to assess the existing level of knowledge of high school children about human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and the sources of their information. Materials and Methods: A cross-sectional survey was conducted in two high schools in Kirikkale, Turkey and data were collected by a self-administered questionnaire. Multi-stage sampling technique was used to obtain a representative sample. Results: Four hundred and seventy three participants; 230 males and 243 females were analyzed. Their ages ranged from 15 to 19 years with a mean age of 16.81 ± 1.27. 92.2% of the students claimed to have heard about HIV/AIDS prior to the study with slightly more females than males. Although with some misconceptions, majority of the participants knew that HIV is not transmitted by sharing meals, casual contact, and sleeping in the same room and using the same bathroom. 93.4% identi?ed HIV/AIDS as a life-threatening disease and 27% believe that there is a cure for AIDS. 64% and 22.8% respectively believed that the people can protect themselves by using condoms and by avoiding sexual contact. Internet was preponderantly claimed as the most important source of information about HIV/AIDS. Conclusion: Empirical evidence from this study suggests that the students have a fairly high knowledge of HIV/AIDS. This is not without some misconceptions about the prognosis of the disease. Internet was the major source of HIV/AIDS information. PMID:23633840

Ayl?kç?, Bahad?r U?ur; Bamise, Cornelius Tokunbo; Hamidi, Mehmet Mustafa; Turkal, Mustafa; Çolak, Hakan

2013-01-01

356

Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV.  

PubMed

RT-SHIV is a chimera of simian immunodeficiency virus (SIV) containing the reverse transcriptase (RT)-encoding region of human immunodeficiency virus type 1 (HIV-1) within the backbone of SIVmac239. It has been used in a non-human primate model for studies of non-nucleoside RT inhibitors (NNRTI) and highly active antiretroviral therapy (HAART). We and others have identified several mutations that arise in the "foreign" HIV-1 RT of RT-SHIV during in vivo replication. In this study we catalogued amino acid substitutions in the HIV-1 RT and in regions of the SIV backbone with which RT interacts that emerged 30 weeks post-infection from seven RT-SHIV-infected rhesus macaques. The virus set points varied from relatively high virus load, moderate virus load, to undetectable virus load. The G196R substitution in RT was detected from 6 of 7 animals at week 4 post-infection and remained in virus from 4 of 6 animals at week 30. Virus from four high virus load animals showed several common mutations within RT, including L74V or V75L, G196R, L214F, and K275R. The foreign RT from high virus load isolates exhibited as much variation as that of the highly variable envelope surface glycoprotein, and 10-fold higher than that of the native RT of SIVmac239. Isolates from moderate virus load animals showed much less variation in the foreign RT than the high virus load isolates. No variation was found in SIVmac239 genes known to interact with RT. Our results demonstrate substantial adaptation of the foreign HIV-1 RT in RT-SHIV-infected macaques, which most likely reflects selective pressure upon the foreign RT to attain optimal activity within the context of the chimeric RT-SHIV and the rhesus macaque host. PMID:24498008

Wadford, Debra A; Kauffman, Robert C; Deere, Jesse D; Aoki, Scott T; Stanton, Richard A; Higgins, Joanne; Van Rompay, Koen K A; Villalobos, Andradi; Nettles, James H; Schinazi, Raymond F; Pedersen, Niels C; North, Thomas W

2014-01-01

357

Gamma/Delta T-cell functional responses differ after pathogenic human immunodeficiency virus and nonpathogenic simian immunodeficiency virus infections.  

PubMed

The objective of this study was to functionally assess gamma/delta (gammadelta) T cells following pathogenic human immunodeficiency virus (HIV) infection of humans and nonpathogenic simian immunodeficiency virus (SIV) infection of sooty mangabeys. gammadelta T cells were obtained from peripheral blood samples from patients and sooty mangabeys that exhibited either a CD4-healthy (>200 CD4(+) T cells/mul blood) or CD4-low (<200 CD4 cells/mul blood) phenotype. Cytokine flow cytometry was utilized to assess production of Th1 cytokines tumor necrosis factor alpha and gamma interferon following ex vivo stimulation with either phorbol myristate acetate/ionomycin or the Vdelta2 gammadelta T-cell receptor agonist isopentenyl pyrophosphate. Sooty mangabeys were observed to have higher percentages of gammadelta T cells in their peripheral blood than humans did. Following stimulation, gammadelta T cells from SIV-positive (SIV(+)) mangabeys maintained or increased their ability to express the Th1 cytokines regardless of CD4(+) T-cell levels. In contrast, HIV-positive (HIV(+)) patients exhibited a decreased percentage of gammadelta T cells expressing Th1 cytokines following stimulation. This dysfunction is primarily within the Vdelta2(+) gammadelta T-cell subset which incurred both a decreased overall level in the blood and a reduced Th1 cytokine production. Patients treated with highly active antiretroviral therapy exhibited a partial restoration in their gammadelta T-cell Th1 cytokine response that was intermediate between the responses of the uninfected and HIV(+) patients. The SIV(+) sooty mangabey natural hosts, which do not proceed to clinical AIDS, provide evidence that gammadelta T-cell dysfunction occurs in HIV(+) patients and may contribute to HIV disease progression. PMID:18045946

Kosub, David A; Lehrman, Ginger; Milush, Jeffrey M; Zhou, Dejiang; Chacko, Elizabeth; Leone, Amanda; Gordon, Shari; Silvestri, Guido; Else, James G; Keiser, Philip; Jain, Mamta K; Sodora, Donald L

2008-02-01

358

Variation of Human Immunodeficiency Virus Type-1 Reverse Transcriptase within the Simian Immunodeficiency Virus Genome of RT-SHIV  

PubMed Central

RT-SHIV is a chimera of simian immunodeficiency virus (SIV) containing the reverse transcriptase (RT)-encoding region of human immunodeficiency virus type 1 (HIV-1) within the backbone of SIVmac239. It has been used in a non-human primate model for studies of non-nucleoside RT inhibitors (NNRTI) and highly active antiretroviral therapy (HAART). We and others have identified several mutations that arise in the "foreign" HIV-1 RT of RT-SHIV during in vivo replication. In this study we catalogued amino acid substitutions in the HIV-1 RT and in regions of the SIV backbone with which RT interacts that emerged 30 weeks post-infection from seven RT-SHIV-infected rhesus macaques. The virus set points varied from relatively high virus load, moderate virus load, to undetectable virus load. The G196R substitution in RT was detected from 6 of 7 animals at week 4 post-infection and remained in virus from 4 of 6 animals at week 30. Virus from four high virus load animals showed several common mutations within RT, including L74V or V75L, G196R, L214F, and K275R. The foreign RT from high virus load isolates exhibited as much variation as that of the highly variable envelope surface glycoprotein, and 10-fold higher than that of the native RT of SIVmac239. Isolates from moderate virus load animals showed much less variation in the foreign RT than the high virus load isolates. No variation was found in SIVmac239 genes known to interact with RT. Our results demonstrate substantial adaptation of the foreign HIV-1 RT in RT-SHIV-infected macaques, which most likely reflects selective pressure upon the foreign RT to attain optimal activity within the context of the chimeric RT-SHIV and the rhesus macaque host. PMID:24498008

Wadford, Debra A.; Kauffman, Robert C.; Deere, Jesse D.; Aoki, Scott T.; Stanton, Richard A.; Higgins, Joanne; Van Rompay, Koen K. A.; Villalobos, Andradi; Nettles, James H.; Schinazi, Raymond F.; Pedersen, Niels C.; North, Thomas W.

2014-01-01

359

In vivo distribution of the human immunodeficiency virus/simian immunodeficiency virus coreceptors: CXCR4, CCR3, and CCR5.  

PubMed

We have evaluated the in vivo distribution of the major human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) coreceptors, CXCR4, CCR3, and CCR5, in both rhesus macaques and humans. T lymphocytes and macrophages in both lymphoid and nonlymphoid tissues are the major cell populations expressing HIV/SIV coreceptors, reaffirming that these cells are the major targets of HIV/SIV infection in vivo. In lymphoid tissues such as the lymph node and the thymus, approximately 1 to 10% of the T lymphocytes and macrophages are coreceptor positive. However, coreceptor expression was not detected on follicular dendritic cells (FDC) in lymph nodes, suggesting that the ability of FDC to trap extracellular virions is unlikely to be mediated by a coreceptor-specific mechanism. In the thymus, a large number of immature and mature T lymphocytes express CXCR4, which may render these cells susceptible to infection by syncytium-inducing viral variants that use this coreceptor for entry. In addition, various degrees of coreceptor expression are found among different tissues and also among different cells within the same tissues. Coreceptor-positive cells are more frequently identified in the colon than in the rectum and more frequently identified in the cervix than in the vagina, suggesting that the expression levels of coreceptors are differentially regulated at different anatomic sites. Furthermore, extremely high levels of CXCR4 and CCR3 expression are found on the neurons from both the central and peripheral nervous systems. These findings may be helpful in understanding certain aspects of HIV and SIV pathogenesis and transmission. PMID:9573273

Zhang, L; He, T; Talal, A; Wang, G; Frankel, S S; Ho, D D

1998-06-01

360

Progressive multifocal leukoence-phalopathy presenting as homonymous hemianopia in a patient with acquired immunodeficiency syndrome  

PubMed Central

We present a case of a Human Immunodeficiency Virus (HIV) positive patient who was referred for retinal evaluation to rule out ophthalmic manifestations of Acquired Immunodeficiency Syndrome (AIDS). She complained of some disturbance in vision in both eyes. Fundus examination showed no abnormality. Perimetry, done to rule out optic nerve pathology, showed a left homonymous hemianopia. Magnetic Resonance Imaging (MRI) scan showed features of Progressive Multifocal Leukoencephalopathy (PML). She had no other neurological symptoms or signs. PMID:23202405

Pandey, Amit; Bandivdekar, Karishma; Ramchandani, Suresh; Ramchandani, Sushama

2012-01-01

361

Invasive infection with Mycobacterium genavense in three children with the acquired immunodeficiency syndrome  

Microsoft Academic Search

Three children with human immunodeficiency virus infection and invasive infection withMycobacterium genavense are reported. Fever spikes, abdominal cramps and distension, diarrhea or ileus, and anemia were the predominant symptoms in the severely immunodeficient patients (CD4 lymphocytes9\\/l). Numerous acid-fast bacilli were readily detectable by microscopy in stool samples and in lymph node biopsies, but cultures for mycobacteria remained negative.Mycobacterium genavense should

D. Nadal; R. Caduff; R. Kraft; M. Salfinger; T. Bodmer; P. Kirschner; E. C. Böttger; U. B. Schaad

1993-01-01

362

Filtration sizes of human immunodeficiency virus type 1 and surrogate viruses used to test barrier materials.  

PubMed Central

Filters with well-defined holes were used to determine the effective diameters in buffer of human immunodeficiency virus type 1, herpes simplex virus type 1, and four bacteriophages (phi X174, T7, PRD1, and phi 6), which may serve as surrogate viruses for testing barrier materials. Bacteriophages phi 6 and PRD1 most closely model human immunodeficiency virus type 1 in filtration size. PMID:1610199

Lytle, C D; Tondreau, S C; Truscott, W; Budacz, A P; Kuester, R K; Venegas, L; Schmukler, R E; Cyr, W H

1992-01-01

363

Dose response effects of feline immunodeficiency virus PPR strain infection in cats  

E-print Network

- Slattery, D. Brousset, and S. J. O' Brien. 1996. Genetic and polygenetic divergence of feline immunodeficiency virus in the puma (Puma concolor). J Virol. 70(10):6682-6693. 11. Dalgleish, A. G. , P. C. Beverly, P. R. Clapham, D. H. Crawford, M. F... deficiency disease in cats similar to human AIDS, also caused by a lentivirus, human immunodeficiency virus (HIV). Serological surveys have revealed FIV-specific antibodies in symptomatic and asymptomatic domestic felids world-wide, as well as, in pumas...

Hokanson, Regina Marie

1998-01-01

364

Central Nervous System Correlates of Behavioral Deficits Following Simian Immunodeficiency Virus Infection  

Microsoft Academic Search

Despite the high incidence of cognitive and motor impairment in acquired im- munodeficiency syndrome (AIDS) patients, the mechanisms of AIDS-related central nervous system (CNS) pathology are not completely understood. Infec- tion with simian immunodeficiency virus (SIV) in macaques provides an excel- lent model of AIDS, including human immunodeficiency virus (HIV)-induced CNS pathology and cognitive\\/behavioral impairment. Co-inoculation with two SIV strains,

Michael R Weed; Robert D Hienz; Joseph V Brady; Robert J Adams; Joseph L Mankowski; Janice E Clements; M Christine Zink

2003-01-01

365

Ocular examination and diagnosis in patients with the acquired immunodeficiency syndrome.  

PubMed Central

Ocular involvement is seen frequently and is an important source of morbidity in patients with the acquired immunodeficiency syndrome. We outline here the general skills of physical diagnosis valuable to primary care physicians or infectious diseases specialists in recognizing and evaluating ocular complaints in patients infected with the human immunodeficiency virus. We provide an overview of common ocular diseases in these patients, with an emphasis on signs and symptoms that aid in the differential diagnosis. Images PMID:8384763

Gariano, R F; Rickman, L S; Freeman, W R

1993-01-01

366

Successful Handling of Disseminated BCG Disease in a Child with Severe Combined Immunodeficiency  

PubMed Central

In high-burden countries, Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine is administered in newborn to prevent severe Mycobacterium tuberculosis infection. Because life-threatening disseminated BCG disease may occur in children with primary immunodeficiency, vaccination strategy against tuberculosis should be redefined in non-high-burden countries. We report the case of a patient with X-linked severe combined immunodeficiency (SCID) who developed disseminated BCG disease, highlighting the specific strategies adopted. PMID:22110512

Bacalhau, Sílvia; Freitas, Cristina; Valente, Rosalina; Barata, Deolinda; Neves, Conceição; Schäfer, Katrin; Lubatschofski, Annelie; Schulz, Ansgar; Neves, João Farela

2011-01-01

367

Shared Usage of the Chemokine Receptor CXCR4 by the Feline and Human Immunodeficiency Viruses  

Microsoft Academic Search

Feline immunodeficiency virus (FIV) induces a disease state in the domestic cat that is similar to AIDS in human immunodeficiency virus (HIV)-infected individuals. As with HIV, FIV can be divided into primary and cell culture-adapted isolates. Adaptation of FIV to replicate and form syncytia in the Crandell feline kidney (CrFK) cell line is accompanied by an increase in the net

BRIAN J. WILLETT; LAURENT PICARD; MARGARET J. HOSIE; JULIE D. TURNER; KAREN ADEMA; PAUL R. CLAPHAM

1997-01-01

368

Mamu-B*08Positive Macaques Control Simian Immunodeficiency Virus Replication  

Microsoft Academic Search

Certain major histocompatibility complex (MHC) class I alleles are associated with the control of human immunodeficiency virus and simian immunodeficiency virus (SIV) replication. We have designed sequence-specific primers for detection of the rhesus macaque MHC class I allele Mamu-B*08 by PCR and screened a cohort of SIV-infected macaques for this allele. Analysis of 196 SIVmac239-infected Indian rhesus macaques revealed that

John T. Loffredo; Jess Maxwell; Ying Qi; Chrystal E. Glidden; Gretta J. Borchardt; Taeko Soma; Alex T. Bean; Dominic R. Beal; Nancy A. Wilson; William M. Rehrauer; Jeffrey D. Lifson; Mary Carrington; David I. Watkins

2007-01-01

369

Evidence for Viral Virulence as a Predominant Factor Limiting Human Immunodeficiency Virus Vaccine Efficacy  

Microsoft Academic Search

Current strategies in human immunodeficiency virus type 1 (HIV-1) vaccine development are often based on the production of different vaccine antigens according to particular genetic clades of HIV-1 variants. To determine if virus virulence or genetic distance had a greater impact on HIV-1 vaccine efficacy, we designed a series of heterologous chimeric simian\\/human immunodeficiency virus (SHIV) challenge experiments in HIV-1

PETRA MOOIJ; WILLY M. J. M. BOGERS; HERMAN OOSTERMEIJER; WIM KOORNSTRA; PETER J. F. TEN HAAFT; BABS E. VERSTREPEN; GERT VAN DER AUWERA; JONATHAN L. HEENEY

2000-01-01

370

Infection of macaques with chimeric simian and human immunodeficiency viruses containing Env from subtype F  

Microsoft Academic Search

Summary.  ?Chimeric simian and human immunodeficiency viruses (SHIVs) are useful for investigating the pathogenicity of human immunodeficiency\\u000a virus (HIV-1) and to develop an anti-HIV-1 vaccine. We attempted to construct SHIVs containing Env from various subtypes,\\u000a because almost all SHIVs which have been reported so far have Env from HIV-1 that belongs to subtype B. Two infectious SHIVs\\u000a containing Env from two

T. Kuwata; T. Takemura; J. Takehisa; T. Miura; M. Hayami

2002-01-01

371

Umbilical Cord Blood Transplantation in Severe T-Cell Immunodeficiency Disorders: Two-Year Experience  

Microsoft Academic Search

Hematopoietic stem cell transplantation is the treatment of choice for severe primary T-cell immunodeficiencies. When an HLA-identical sibling as the donor is not available, an alternative donor stem cell source is needed. In primary T-cell immunodeficiencies, T-cell-depleted HLA-haploidentical bone marrow transplantation has been particularly successful in reconstituting the immune system in many but not all of the severe T-cell immune

Alan P. Knutsen; Donna A. Wall

2000-01-01

372

Feline Immunodeficiency Virus Xenoinfection: the Role of Chemokine Receptors and Envelope Diversity  

Microsoft Academic Search

Received 25 May 2001\\/Accepted 11 January 2002 The use of chemokine receptors as cell recognition signals is a property common to several lentiviruses, including feline, human, and simian immunodeficiency viruses. Previously, two feline immunodeficiency virus (FIV) isolates, V1CSF and Petaluma, were shown to use chemokine receptors in a strain-dependent manner to infect human peripheral blood mononuclear cells (PBMC) (J. Johnston

J. B. Johnston; C. Power

2002-01-01

373

Tumor necrosis factor alpha inhibits entry of human immunodeficiency virus type 1 into primary human macrophages: a selective role for the 75-kilodalton receptor.  

PubMed

The proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) is readily detected after human immunodeficiency virus type 1 (HIV-1) infection of primary macrophages in vitro and is present in plasma and tissues of patients with AIDS. Previous studies have shown that human recombinant TNFalpha (hrTNFalpha) enhances HIV replication in both chronically infected promonocytic and T-lymphoid cell lines in vitro. We report here that in contrast to untreated tissue culture-differentiated macrophages (TCDM), in which the proviral long terminal repeat (LTR) could be detected as soon as 8 h postinfection by a PCR assay, TCDM pretreatment for 3 days by hrTNFalpha markedly delayed its appearance until 72 h after infection with the HIV-1 Ada monocytotropic strain. Moreover the inhibition of formation of the proviral LTR in HIV-1-infected TCDM was directly proportional to the concentration of hrTNFalpha used. To determine if the inhibition of LTR formation results from blockade of viral entry, we performed a reverse transcription PCR assay to detect intracellular genomic viral RNA as early as 2 h after infection. Pretreatment of primary TCDM by hrTNFalpha for 3 days and even for only 2 h inhibits 75% of the viral entry into the cells. The inhibition of viral entry by hrTNFalpha was totally abolished by the use of anti-human TNFalpha monoclonal antibody. By using TNFalpha mutants specific for each human TNFalpha receptor, we showed that the inhibition of HIV-1 entry into TCDM was mediated not through the 55-kDa TNF receptor but through the 75-kDa TNF receptor. Although prolonged (1 to 5 days) TNFalpha treatment can downregulate CD4 expression in primary human TCDM, surface CD4 levels were not reduced by 2 h of treatment and was therefore not a limiting step for HIV-1 entry. In contrast to the inhibition of viral entry into primary TCDM, pretreatment with hrTNFalpha did not modify HIV-1 entry into phytohemagglutinin A-activated peripheral blood lymphocytes. TNFalpha-pretreatment inhibited HIV-1 replication in primary TCDM but not in phytohemagglutinin A-activated peripheral blood lymphocytes as assessed by decreased reverse transcriptase activity in culture supernatants. These results demonstrate that TNFalpha is able to enhance host cellular resistance to HIV-1 infection and that selective inhibition of HIV-1 entry into primary TCDM by TNFalpha involves the 75-kDa TNF receptor but not the 55-kDa TNF receptor. PMID:8892857

Herbein, G; Montaner, L J; Gordon, S

1996-11-01

374

Tumor necrosis factor alpha inhibits entry of human immunodeficiency virus type 1 into primary human macrophages: a selective role for the 75-kilodalton receptor.  

PubMed Central

The proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) is readily detected after human immunodeficiency virus type 1 (HIV-1) infection of primary macrophages in vitro and is present in plasma and tissues of patients with AIDS. Previous studies have shown that human recombinant TNFalpha (hrTNFalpha) enhances HIV replication in both chronically infected promonocytic and T-lymphoid cell lines in vitro. We report here that in contrast to untreated tissue culture-differentiated macrophages (TCDM), in which the proviral long terminal repeat (LTR) could be detected as soon as 8 h postinfection by a PCR assay, TCDM pretreatment for 3 days by hrTNFalpha markedly delayed its appearance until 72 h after infection with the HIV-1 Ada monocytotropic strain. Moreover the inhibition of formation of the proviral LTR in HIV-1-infected TCDM was directly proportional to the concentration of hrTNFalpha used. To determine if the inhibition of LTR formation results from blockade of viral entry, we performed a reverse transcription PCR assay to detect intracellular genomic viral RNA as early as 2 h after infection. Pretreatment of primary TCDM by hrTNFalpha for 3 days and even for only 2 h inhibits 75% of the viral entry into the cells. The inhibition of viral entry by hrTNFalpha was totally abolished by the use of anti-human TNFalpha monoclonal antibody. By using TNFalpha mutants specific for each human TNFalpha receptor, we showed that the inhibition of HIV-1 entry into TCDM was mediated not through the 55-kDa TNF receptor but through the 75-kDa TNF receptor. Although prolonged (1 to 5 days) TNFalpha treatment can downregulate CD4 expression in primary human TCDM, surface CD4 levels were not reduced by 2 h of treatment and was therefore not a limiting step for HIV-1 entry. In contrast to the inhibition of viral entry into primary TCDM, pretreatment with hrTNFalpha did not modify HIV-1 entry into phytohemagglutinin A-activated peripheral blood lymphocytes. TNFalpha-pretreatment inhibited HIV-1 replication in primary TCDM but not in phytohemagglutinin A-activated peripheral blood lymphocytes as assessed by decreased reverse transcriptase activity in culture supernatants. These results demonstrate that TNFalpha is able to enhance host cellular resistance to HIV-1 infection and that selective inhibition of HIV-1 entry into primary TCDM by TNFalpha involves the 75-kDa TNF receptor but not the 55-kDa TNF receptor. PMID:8892857

Herbein, G; Montaner, L J; Gordon, S

1996-01-01

375

Energy distribution and flux of fast neutrals and residual ions extracted from a neutral beam source  

E-print Network

alternative, the neutral beam energy and flux need to be comparable to those in RIE. Earlier designs8Energy distribution and flux of fast neutrals and residual ions extracted from a neutral beam-4004 Received 21 April 2006; accepted 6 July 2006; published 7 August 2006 The energy distribution and flux

Economou, Demetre J.

376

Derivation of the relationship between neutral mutation and fixation solely from the definition of selective neutrality  

Microsoft Academic Search

A mutation whose fixation is independent of natural selection is termed a neutral mutation. Therefore selective neutrality of a mutation can be defined by independence of its fixation from natural selection. By the population genetic approach, Kimura [Kimura, M. (1962) Genetics 47, 713-719] predicted that the probability of fixation of a neutral mutation (u) is equal to the frequency of

Jun-Ichi Tomizawa

2000-01-01

377

A self-consistent model of plasma and neutrals at Saturn: Neutral cloud morphology  

Microsoft Academic Search

We present a model of the plasma and neutral environment that treats plasma and neutrals self-consistently, using Voyager plasma and ultraviolet H observations and Hubble Space Telescope OH measurements as constraints. The neutral distributions are determined with a Monte Carlo model, and the plasma distributions are determined with a diffusive transport model including sources and losses. We find a larger

S. Jurac; J. D. Richardson

2005-01-01

378

Phase I and II Study of the Safety, Virologic Effect, and Pharmacokinetics/Pharmacodynamics of Single-Dose 3-O-(3?,3?-Dimethylsuccinyl)Betulinic Acid (Bevirimat) against Human Immunodeficiency Virus Infection?  

PubMed Central

Bevirimat [3-O-(3?,3?-dimethylsuccinyl)betulinic acid] is the first in a new class of anti-human immunodeficiency virus (HIV) drugs that inhibit viral maturation by specifically blocking cleavage of the Gag capsid (CA) precursor, CA-SP1, to mature CA protein, resulting in defective core condensation and release of immature noninfectious virions. Four cohorts of six HIV-infected adults, with CD4 counts of >200 and plasma viral loads of 5,000 to 250,000 transcripts/ml and not currently receiving antiretroviral therapy, were randomized to receive a single oral dose of placebo, 75, 150, or 250 mg of bevirimat. Thirty blood samples for drug concentrations and 20 HIV RNA measures were collected from each subject over a 20-day period. Candidate pharmacokinetic/pharmacodynamic models were fit to individual subjects by maximum likelihood followed by Bayesian estimation; model discrimination was by corrected Akaike's Information Criterion. The bevirimat pharmacokinetics was well described by an oral two-compartment linear model (r2, 0.98), with a mean (percent coefficient of variation) half-life of 60.3 (13.6) h and apparent oral clearance of bevirimat from the plasma compartment of 0.17 (18) liters/h. HIV RNA was modeled as being produced in infected CD4 cells, with bevirimat inhibiting infection of new CD4 cells thru a Hill-type function (r2, 0.87). Single oral doses of bevirimat were well tolerated and demonstrated a dose-dependent reduction in viral load. The average maximum reduction from baseline following the 150- and 250-mg doses was greater than 0.45 log10, with individual patients having reductions of greater than 0.7 log10. No bevirimat resistance mutations were detected during the course of the study. PMID:17638699

Smith, Patrick F.; Ogundele, Abayomi; Forrest, Alan; Wilton, John; Salzwedel, Karl; Doto, Judy; Allaway, Graham P.; Martin, David E.

2007-01-01

379

Encapsulation of Neutral Gold Nanoclusters by Resorcinarenes  

E-print Network

Letters Encapsulation of Neutral Gold Nanoclusters by Resorcinarenes Kevin B. Stavens, Stephen V for encapsulating neutral nanoclusters is presented which employs surfactants with large concave headgroups and multiple contact sites. Au nanoclusters ranging from 3 to 20 nm in diameter were generated in the vapor

Wei, Alexander

380

32 CFR 644.323 - Neutral language.  

Code of Federal Regulations, 2010 CFR

...Defense 4 2010-07-01 2010-07-01 true Neutral language. 644.323 Section 644.323 National Defense Department...PROPERTY REAL ESTATE HANDBOOK Disposal § 644.323 Neutral language. Wherever the words “man”, “men”, or their...

2010-07-01

381

32 CFR 644.323 - Neutral language.  

Code of Federal Regulations, 2011 CFR

...Defense 4 2011-07-01 2011-07-01 false Neutral language. 644.323 Section 644.323 National Defense Department...PROPERTY REAL ESTATE HANDBOOK Disposal § 644.323 Neutral language. Wherever the words “man”, “men”, or their...

2011-07-01

382

SPECIAL FEATURE Neutral Community Ecology1  

E-print Network

to community structure and diversity patterns. While stochasticity has long been incorporated formallySPECIAL FEATURE Neutral Community Ecology1 Interest in neutral community models has grown rapidly broadly studied community patterns like rank abundance distributions and species­area relationships. Most

Holyoak, Marcel

383

Generation and characterization of infectious chimeric clones between human immunodeficiency virus type 1 and simian immunodeficiency virus from an African green monkey.  

PubMed Central

A series of chimeric clones of human immunodeficiency virus type 1 and simian immunodeficiency virus isolated from an African green monkey was constructed in vitro. In transient transfection experiments, all clones produced virion-associated reverse transcriptase, gag proteins, and env proteins. Eight out of 10 chimeric viruses clearly grew in the human CD4+ cell line C8166. Susceptibility of other CD4+ cell lines, MT-4, A3.01, and Molt4 clone 8, to infection with these viruses was also demonstrated. Images PMID:1700827

Shibata, R; Sakai, H; Kiyomasu, T; Ishimoto, A; Hayami, M; Adachi, A

1990-01-01

384

Neutral depletion and the helicon density limit  

SciTech Connect

It is straightforward to create fully ionized plasmas with modest rf power in a helicon. It is difficult, however, to create plasmas with density >10{sup 20} m{sup ?3}, because neutral depletion leads to a lack of fuel. In order to address this density limit, we present fast (1 MHz), time-resolved measurements of the neutral density at and downstream from the rf antenna in krypton helicon plasmas. At the start of the discharge, the neutral density underneath the antenna is reduced to 1% of its initial value in 15 ?s. The ionization rate inferred from these data implies that the electron temperature near the antenna is much higher than the electron temperature measured downstream. Neutral density measurements made downstream from the antenna show much slower depletion, requiring 14 ms to decrease by a factor of 1/e. Furthermore, the downstream depletion appears to be due to neutral pumping rather than ionization.

Magee, R. M.; Galante, M. E.; Carr, J. Jr.; Lusk, G.; McCarren, D. W.; Scime, E. E. [West Virginia University, Morgantown, West Virginia 26506 (United States)] [West Virginia University, Morgantown, West Virginia 26506 (United States)

2013-12-15

385

Neutral depletion and the helicon density limit  

NASA Astrophysics Data System (ADS)

It is straightforward to create fully ionized plasmas with modest rf power in a helicon. It is difficult, however, to create plasmas with density >1020 m-3, because neutral depletion leads to a lack of fuel. In order to address this density limit, we present fast (1 MHz), time-resolved measurements of the neutral density at and downstream from the rf antenna in krypton helicon plasmas. At the start of the discharge, the neutral density underneath the antenna is reduced to 1% of its initial value in 15 ?s. The ionization rate inferred from these data implies that the electron temperature near the antenna is much higher than the electron temperature measured downstream. Neutral density measurements made downstream from the antenna show much slower depletion, requiring 14 ms to decrease by a factor of 1/e. Furthermore, the downstream depletion appears to be due to neutral pumping rather than ionization.

Magee, R. M.; Galante, M. E.; Carr, J.; Lusk, G.; McCarren, D. W.; Scime, E. E.

2013-12-01

386

The status of neutral currents  

SciTech Connect

The situation of particle physics today is quite puzzling. On the one hand, the Standard Model (SM) of strong and electroweak interactions is consistent with all confirmed experimental data but theoretically rather unsatisfactory. On the other hand, none of the many theoretical speculations which try to go beyond the SM has (yet) received the slightest experimental support. The solution to this dilemma can only come from new data: either from the detection of a new particle threshold at high energy colliders, or from the appearance of some small discrepancy in high-precision experiments. A crucial sector for testing the SM and its extensions is that of neutral currents (NC), where an impressive amount of data has been collected in recent years. While waiting for the next generation of experiments, it is certainly useful to take stock of our knowledge, determining the NC parameters as precisely as we can and putting limits on possible deviations from the SM. The present talk contains the results of a recent analysis along these lines: the first part illustrates how a set of 'model-independent' parameters can be extracted from the available NC data, the second part particularizes the analysis to the SM and to some superstring-inspired models with an additional Z' in their low-energy spectrum. 27 refs., 3 figs., 1 tab.

Zwirner, F.

1987-11-01

387

Selection of a rare neutralization-resistant variant following passive transfer of convalescent immune plasma in equine infectious anemia virus-challenged SCID horses.  

PubMed

Vaccines preventing HIV-1 infection will likely elicit antibodies that neutralize diverse strains. However, the capacity for lentiviruses to escape broadly neutralizing antibodies (NAbs) is not completely understood, nor is it known whether NAbs alone can control heterologous infection. Here, we determined that convalescent immune plasma from a horse persistently infected with equine infectious anemia virus (EIAV) neutralized homologous virus and several envelope variants containing heterologous principal neutralizing domains (PND). Plasma was infused into young horses (foals) affected with severe combined immunodeficiency (SCID), followed by challenge with a homologous EIAV stock. Treated SCID foals were protected against clinical disease, with complete prevention of infection occurring in one foal. In three SCID foals, a novel neutralization-resistant variant arose that was found to preexist at a low frequency in the challenge inoculum. In contrast, SCID foals infused with nonimmune plasma developed acute disease associated with high levels of the predominant challenge virus. Following transfer to an immunocompetent horse, the neutralization-resistant variant induced a single febrile episode and was subsequently controlled in the absence of type-specific NAb. Long-term control was associated with the presence of cytotoxic T lymphocytes (CTL). Our results demonstrate that immune plasma with neutralizing activity against heterologous PND variants can prevent lentivirus infection and clinical disease in the complete absence of T cells. Importantly, however, rare neutralization-resistant envelope variants can replicate in vivo under relatively broad selection pressure, highlighting the need for protective lentivirus vaccines to elicit NAb responses with increased breadth and potency and/or CTL that target conserved epitopes. PMID:20392850

Taylor, Sandra D; Leib, Steven R; Carpenter, Susan; Mealey, Robert H

2010-07-01

388

Gas Flow in the Neutralization Region of EAST Neutral Beam Injector  

NASA Astrophysics Data System (ADS)

The gas flow in the neutralization region affects the neutralization efficiency as well as the beam transition efficiency of whole neutral beam injector, which will be applied as a high power auxiliary heating and non-inductive current driver system for the Experimental Advanced Superconducting Tokamak (EAST). The neutralization region of EAST neutral beam injector includes not only the gas cell neutralizer in traditional sense, but also part of the ion source downstream the electrode grid, the gate valve, and the transitional piping and fitting. The gas flow in this neutralization region has been modeled and researched using an adjusted Direct Simulation Monte Carlo code to understand the formation mechanism of gas target thickness, which determines the neutralization efficiency. This paper presents the steady-state, viscous and transition region flowfields, the gas density distribution and the various centerline profiles including Knudsen number, temperature, pressure and axial velocity by injected the deuterium gas from the arc chamber and neutralizer, respectively. The target thickness in the neutralization region as a function of gas inlet quantity is also given in the absence of beam for future operation of EAST neutral beam injector.

Wei, Jiang-Long; Hu, Chun-Dong; Liang, Li-Zhen; Xie, Yuan-Lai

2013-04-01

389

Impact of Simian Immunodeficiency Virus Infection on Chimpanzee Population Dynamics  

PubMed Central

Like human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus of chimpanzees (SIVcpz) can cause CD4+ T cell loss and premature death. Here, we used molecular surveillance tools and mathematical modeling to estimate the impact of SIVcpz infection on chimpanzee population dynamics. Habituated (Mitumba and Kasekela) and non-habituated (Kalande) chimpanzees were studied in Gombe National Park, Tanzania. Ape population sizes were determined from demographic records (Mitumba and Kasekela) or individual sightings and genotyping (Kalande), while SIVcpz prevalence rates were monitored using non-invasive methods. Between 2002–2009, the Mitumba and Kasekela communities experienced mean annual growth rates of 1.9% and 2.4%, respectively, while Kalande chimpanzees suffered a significant decline, with a mean growth rate of ?6.5% to ?7.4%, depending on population estimates. A rapid decline in Kalande was first noted in the 1990s and originally attributed to poaching and reduced food sources. However, between 2002–2009, we found a mean SIVcpz prevalence in Kalande of 46.1%, which was almost four times higher than the prevalence in Mitumba (12.7%) and Kasekela (12.1%). To explore whether SIVcpz contributed to the Kalande decline, we used empirically determined SIVcpz transmission probabilities as well as chimpanzee mortality, mating and migration data to model the effect of viral pathogenicity on chimpanzee population growth. Deterministic calculations indicated that a prevalence of greater than 3.4% would result in negative growth and eventual population extinction, even using conservative mortality estimates. However, stochastic models revealed that in representative populations, SIVcpz, and not its host species, frequently went extinct. High SIVcpz transmission probability and excess mortality reduced population persistence, while intercommunity migration often rescued infected communities, even when immigrating females had a chance of being SIVcpz infected. Together, these results suggest that the decline of the Kalande community was caused, at least in part, by high levels of SIVcpz infection. However, population extinction is not an inevitable consequence of SIVcpz infection, but depends on additional variables, such as migration, that promote survival. These findings are consistent with the uneven distribution of SIVcpz throughout central Africa and explain how chimpanzees in Gombe and elsewhere can be at equipoise with this pathogen. PMID:20886099

Rudicell, Rebecca S.; Holland Jones, James; Wroblewski, Emily E.; Learn, Gerald H.; Li, Yingying; Robertson, Joel D.; Greengrass, Elizabeth; Grossmann, Falk; Kamenya, Shadrack; Pintea, Lilian; Mjungu, Deus C.; Lonsdorf, Elizabeth V.; Mosser, Anna; Lehman, Clarence; Collins, D. Anthony; Keele, Brandon F.; Goodall, Jane; Hahn, Beatrice H.; Pusey, Anne E.; Wilson, Michael L.

2010-01-01

390

Human Immunodeficiency Virus and Heparan Sulfate: From Attachment to Entry Inhibition  

PubMed Central

By targeting cells that provide protection against infection, HIV-1 causes acquired immunodeficiency syndrome. Infection starts when gp120, the viral envelope glycoprotein, binds to CD4 and to a chemokine receptor usually CCR5 or CXCR4. As many microorganisms, HIV-1 also interacts with heparan sulfate (HS), a complex group of cell surface associated anionic polysaccharides. It has been thought that this binding, occurring at a step prior to CD4 recognition, increases infectivity by pre-concentrating the virion particles at the cell surface. Early work, dating from before the identification of CCR5 and CXCR4, showed that a variety of HS mimetics bind to the gp120 V3 loop through electrostatic interactions, compete with cell surface associated HS to bind the virus and consequently, neutralize the infectivity of a number of T-cell line-adapted HIV-1 strains. However, progress made to better understand HIV-1 attachment and entry, coupled with the recent identification of additional gp120 regions mediating HS recognition, have considerably modified this view. Firstly, the V3 loop from CXCR4-using viruses is much more positively charged compared to those using CCR5. HS inhibition of cell attachment is thus restricted to CXCR4-using viruses (such as T-cell line-adapted HIV-1). Secondly, studies aiming at characterizing the gp120/HS complex revealed that HS binding was far more complex than previously thought: in addition to the V3 loop of CXCR4 tropic gp120, HS interacts with several other cryptic areas of the protein, which can be induced upon CD4 binding, and are conserved amongst CCR5 and CXCR4 viruses. In view of these data, this review will detail the present knowledge on HS binding to HIV-1, with regards to attachment and entry processes. It will discuss the perspective of targeting the gp120 co-receptor binding site with HS mimetic compounds, a strategy that recently gave rise to entry inhibitors that work in the low nanomolar range, independently of co-receptor usage. PMID:24312095

Connell, Bridgette J.; Lortat-Jacob, Hugues

2013-01-01

391

Replication of an acutely lethal simian immunodeficiency virus activates and induces proliferation of lymphocytes.  

PubMed Central

A variant of simian immunodeficiency virus from sooty mangabey monkeys (SIVsmm), termed SIVsmmPBj14, was previously identified and shown to induce acute disease and death within 1 to 2 weeks of inoculation of pig-tailed macaques and mangabey monkeys (P. N. Fultz, H. M. McClure, D. C. Anderson, and W. M. Switzer, AIDS Res. Hum. Retroviruses 5:397-409, 1989). SIVsmmPBj14 differed from its parent virus, SIVsmm9, not only in pathogenicity but also in multiple in vitro properties. As a first approach to understanding the biological and molecular mechanisms responsible for the acute disease and death induced by this variant, virus-host cell interactions of SIVsmmPBj14 and SIVsmm9 were studied. Initial rates of replication of the two viruses were identical in primary peripheral blood mononuclear cells (PBMC) from normal pig-tailed macaques and mangabey monkeys, but SIVsmmPBj14 infection always resulted in higher yields of virus than did SIVsmm9 infection, as assessed by levels of reverse transcriptase activity in culture supernatants. Surprisingly, despite its cytopathicity for macaque and mangabey CD4+ cells, replication of SIVsmmPBj14 was accompanied by up to 10-fold increases in number of viable cells compared with cell numbers in uninfected or SIVsmm9-infected cultures. Furthermore, SIVsmmPBj14 was shown to infect and replicate in resting PBMC just as efficiently as in mitogen-stimulated PBMC, irrespective of whether exogenous interleukin-2 (IL-2) or antibodies that neutralized IL-2 were added to culture media. Accumulation of virus in culture supernatants of resting PBMC preceded by several days the appearance of activated cells which expressed the IL-2 receptor alpha subunit (CD25), suggesting that activation of cells was not essential for replication. The ability to activate and to induce simian PBMC to proliferate appeared specific for the acutely lethal variant because incorporation of [3H]thymidine by PBMC from naive animals was observed only upon incubation with concentrated, heat-inactivated SIVsmmPBj14 and not with other viruses. Both CD4(+)- and CD8(+)-enriched cell populations proliferated in response to SIVsmmPBj14. These results are consistent with in vivo observations and suggest that the abilities both to replicate in resting cells and to induce lymphocytes to proliferate may contribute to the extreme virulence of SIVsmmPBj14. Images PMID:1870205

Fultz, P N

1991-01-01

392

Treatment of Human Immunodeficiency Virus Infection with Hydroxyurea, Didanosine, and a Protease Inhibitor before Seroconversion Is Associated  

E-print Network

1827 Treatment of Human Immunodeficiency Virus Infection with Hydroxyurea, Didanosine with the combination of hydroxyurea, didanosine, and indinavir. This treatment was associated with the normalization

Lieberman, Judy

393

Cytokine interactions in human immunodeficiency virus-infected individuals: roles of interleukin (IL)-2, IL-12, and IL-15  

PubMed Central

Cytokines have been shown to be powerful regulators of the immune response. In this study, we analyze the effect that the newly recognized cytokine interleukin (IL)-15 has on proliferation and cytokine induction using peripheral blood mononuclear cells (PBMCs) and purified CD4+ T cells from patients infected with human immunodeficiency virus (HIV) who are at various stages in their disease. We observed that IL-15 enhances the proliferative response in a dose-dependent manner from PBMCs of HIV-infected individuals when stimulated by polyclonal mitogen, tetanus toxoid, or HIV-specific antigen. The effects of exogenous IL-15 are substantially diminished by adding a neutralizing antibody to the beta chain of the IL-2 receptor. Moreover, the ability of IL-15 to increase proliferation is enhanced by the presence of endogenous IL-2 produced in the cultures. The effect that exogenous IL-15 had on IL-2, IL-4, and interferon (IFN)-gamma induction from PBMC's or CD4+ T cells in response to mitogen or tetanus toxoid was also examined. This was compared to the effect that exogenous IL-2 and IL-12 had under the same conditions. Addition of IL- 2 or IL-15 to short-term in vitro cultures of either PBMCs or CD4+ T cells had little effect on IL-2, IL-4, or IFN-gamma production. By contrast, IL-12 caused substantial enhancement of both IL-2 and IFN- gamma production from these cultures. The role that endogenous cytokines have on IFN-gamma induction was also studied. Addition of a neutralizing antibody to the alpha chain of the IL-2 receptor or IL-12 to antigen stimulated cultures caused a striking decrease in IFN-gamma production. Neutralization of endogenous IL-15 also resulted in diminished IFN-gamma production from cultures stimulated with mitogen. IL-4 and IFN-gamma protein production by PBMCs and CD4+ T cells stimulated with mitogen was assessed to see if we could detect a specific bias of cytokine production. Small amounts of IL-4 were detected from CD4+ T cells but not PBMCs from most individuals tested. IFN-gamma and IL-2, however, were also produced from these same cultures. These results further elucidate the mechanism of cytokine regulation in HIV-infected individuals, and they provide evidence that IL-15 may be a useful immune modulator. PMID:7561680

1995-01-01

394

A nearly neutral model of biodiversity.  

PubMed

S. P. Hubbell's unified neutral theory of biodiversity has stimulated much new thinking about biodiversity. However, empirical support for the neutral theory is limited, and several observations are inconsistent with the predictions of the theory, including positive correlations between traits associated with competitive ability and species abundance and correlations between species diversity and ecosystem functioning. The neutral theory can be extended to explain these observations by allowing species to differ slightly in their competitive ability (fitness). Here, we show that even slight differences in fecundity can greatly reduce the time to extinction of competitors even when the community size is large and dispersal is spatially limited. In this case, species richness is dramatically reduced, and a markedly different species abundance distribution is predicted than under pure neutrality. In the nearly neutral model, species co-occur in the same community not because of, but in spite of, ecological differences. The more competitive species with higher fecundity tend to have higher abundance both in the metacommunity and in local communities. The nearly neutral perspective provides a theoretical framework that unites the sampling model of the neutral theory with theory of biodiversity affecting ecosystem function. PMID:18376566

Zhou, Shu-Rong; Zhang, Da-Yong

2008-01-01

395

Normal immune function and inability to isolate virus in culture in an individual with long-term human immunodeficiency virus type 1 infection.  

PubMed

A detailed, longitudinal study was undertaken to investigate the immunological and virological features of an individual with hemophilia infected with human immunodeficiency virus type-1 (HIV-1) for 10 years without disease. Methods applied to serial samples of peripheral blood included Western blot analysis, neutralizing antibody assays, antibody-dependent cell-mediated cytotoxicity (ADCC) titration, HIV-1 specific cytotoxic T lymphocyte (CTL) assays, viral cultures, and PCR with sequence analysis of viral regulatory genes. Strong antibody responses against HIV-1 antigens as measured by Western blot and ADCC assays have persisted throughout infection. Repeated attempts to isolate HIV-1 using sensitive culture techniques and to demonstrate viremia with standard PCR methods have failed. Using the "booster" PCR technique, a period of viremia in peripheral blood mononuclear cells was demonstrated. Concurrent with detection of circulating virus, titers of neutralizing antibodies and circulating HIV-1-specific CTLs became measurable. Sequencing studies of a portion of the viral genome showed no significant abnormalities of the regulatory genes. In this individual, the combination of low viral load in the peripheral blood and a strong, responsive immune system is associated with long-term, disease-free coexistence with HIV-1 infection. PMID:8068417

Greenough, T C; Somasundaran, M; Brettler, D B; Hesselton, R M; Alimenti, A; Kirchhoff, F; Panicali, D; Sullivan, J L

1994-04-01

396

Human immunodeficiency virus type 1 infection of the brain.  

PubMed Central

Direct infection of the central nervous system by human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS, was not appreciated in the early years of the AIDS epidemic. Neurological complications associated with AIDS were largely attributed to opportunistic infections that arose as a result of the immunocompromised state of the patient and to depression. In 1985, several groups succeeded in isolating HIV-1 directly from brain tissue. Also that year, the viral genome was completely sequenced, and HIV-1 was found to belong to a neurotropic subfamily of retrovirus known as the Lentivirinae. These findings clearly indicated that direct HIV-1 infection of the central nervous system played a role in the development of AIDS-related neurological disease. This review summarizes the clinical manifestations of HIV-1 infection of the central nervous system and the related neuropathology, the tropism of HIV-1 for specific cell types both within and outside of the nervous system, the possible mechanisms by which HIV-1 damages the nervous system, and the current strategies for diagnosis and treatment of HIV-1-associated neuropathology. Images PMID:8269391

Atwood, W J; Berger, J R; Kaderman, R; Tornatore, C S; Major, E O

1993-01-01

397

The Molecular Biology of Feline Immunodeficiency Virus (FIV)  

PubMed Central

Feline immunodeficiency virus (FIV) is widespread in feline populations and causes an AIDS-like illness in domestic cats. It is highly prevalent in several endangered feline species. In domestic cats FIV infection is a valuable small animal model for HIV infection. In recent years there has been sa significant increase in interest in FIV, in part to exploit this, but also because of the potential it has as a human gene therapy vector. Though much less studied than HIV there are many parallels in the replication of the two viruses, but also important differences and, despite their likely common origin, the viruses have in some cases used alternative strategies to overcome similar problems. Recent advances in understanding the structure and function of FIV RNA and proteins and their interactions has enhanced our knowledge of FIV replication significantly, however, there are still many gaps. This review summarizes our current knowledge of FIV molecular biology and its similarities with, and differences from, other lentiviruses. PMID:22163340

Kenyon, Julia C.; Lever, Andrew M. L.

2011-01-01

398

Early physiological abnormalities after simian immunodeficiency virus infection  

PubMed Central

Central nervous system (CNS) damage and dysfunction are devastating consequences of HIV infection. Although the CNS is one of the initial targets for HIV infection, little is known about early viral-induced abnormalities that can affect CNS function. Here we report the detection of early physiological abnormalities in simian immunodeficiency virus-infected monkeys. The acute infection caused a disruption of the circadian rhythm manifested by rises in body temperature, observed in all five individuals between 1 and 2 weeks postinoculation (p.i.), accompanied by a reduction in daily motor activity to 50% of control levels. Animals remained hyperthermic at 1 and 2 months p.i. and returned to preinoculation temperatures at 3 months after viral inoculation. Although motor activity recovered to baseline values at 1 month p.i., activity levels then decreased to approximately 50% of preinoculation values over the next 2 months. Analysis of sensory-evoked responses 1 month p.i. revealed distinct infection-induced changes in auditory-evoked potential peak latencies that persisted at 3 months after viral inoculation. These early physiological abnormalities may precede the development of observable cognitive or motor deficiencies and can provide an assay to evaluate agents to prevent or alleviate neuronal dysfunction. PMID:9844017

Horn, Thomas F. W.; Huitron-Resendiz, Salvador; Weed, Michael R.; Henriksen, Steven J.; Fox, Howard S.

1998-01-01

399

Successful treatment for West syndrome with severe combined immunodeficiency.  

PubMed

Several immune mechanisms are suspected in the unknown etiology of West syndrome (WS). We report a male infant who suffered from WS and X-linked T-B+NK- severe combined immunodeficiency (X-SCID) with a missense mutation of the IL2RG gene (c.202G>A, p.Glu68Lys). He promptly began vitamin B6 and valproic acid treatment, but infantile spasms (IS) and hypsarrhythmia persisted. Administration of intravenous immunoglobulin and the change to topiramate (TPM) at 7 months of age resulted in the rapid resolution of IS. The CD4/8 ratio in his peripheral blood increased from 0.04-0.09 to 0.20-1.95 following unrelated cord blood transplantation (UCBT). In vitro lymphocyte proliferation in response to phytohemagglutinin or concanavalin A and the ability of B lymphocytes to produce antibodies improved as well. Electroencephalogram findings became normal 1 month after UCBT. Thus, we consider that T-cell dysfunction and/or impairments in T-B cell interactions due to X-SCID may have played important roles in the onset of WS. Immune-modulating therapies along with the administration of TPM effectively treated this severe epileptic syndrome in our patient. PMID:24534054

Motobayashi, Mitsuo; Inaba, Yuji; Fukuyama, Tetsuhiro; Kurata, Takashi; Niimi, Taemi; Saito, Shoji; Shiba, Naoko; Nishimura, Takafumi; Shigemura, Tomonari; Nakazawa, Yozo; Kobayashi, Norimoto; Sakashita, Kazuo; Agematsu, Kazunaga; Ichikawa, Motoki; Koike, Kenichi

2015-01-01

400

Selective Destruction Of Cells Infected With The Human Immunodeficiency Virus  

DOEpatents

Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a varient of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles. Still another preferred embodiment of the invention includes a targeting moiety attached to the variants of the ribosome-inactivating protein to target the agent to HIV infectable cells.

Keener, William K. (Idaho Falls, ID); Ward, Thomas E. (Idaho Falls, ID)

2006-03-28

401

Noninfectious Pulmonary Complications of Human Immunodeficiency Virus Infection  

PubMed Central

Abstract: Human immunodeficiency virus type 1 (HIV-1) is the retrovirus responsible for the development of AIDS. Its profound impact on the immune system leaves the host vulnerable to a wide range of opportunistic infections not seen in individuals with a competent immune system. Pulmonary infections dominated the presentations in the early years of the epidemic, and infectious and noninfectious lung diseases remain the leading causes of morbidity and mortality in persons living with HIV despite the development of effective antiretroviral therapy. In addition to the long known immunosuppression and infection risks, it is becoming increasingly recognized that HIV promotes the risk of noninfectious pulmonary diseases through a number of different mechanisms, including direct tissue toxicity by HIV-related viral proteins and the secondary effects of coinfections. Diseases of the airways, lung parenchyma and the pulmonary vasculature, as well as pulmonary malignancies, are either more frequent in persons living with HIV or have atypical presentations. As the pulmonary infectious complications of HIV are generally well known and have been reviewed extensively, this review will focus on the breadth of noninfectious pulmonary diseases that occur in HIV-infected individuals as these may be more difficult to recognize by general medical physicians and subspecialists caring for this large and uniquely vulnerable population. PMID:24992395

Staitieh, Bashar

2014-01-01

402

Hypogonadism in Human Immunodeficiency Virus-Positive Men  

PubMed Central

In recent years, the life expectancy for those living with human immunodeficiency virus (HIV) with access to combined antiretroviral therapy (cART) has increased. As men live longer, the role testosterone plays in sexual function as well as in general well-being is becoming increasingly important. Here we discuss the available literature concerning androgens and HIV disease. A review was undertaken by using a PubMed search with the umbrella terms HIV or AIDS and testosterone or androgens spanning 1985 to 2011. Significant articles found in references in the primary search were also included. The reported prevalence of androgen deficiency appears to be greater in HIV-infected males than in the general population. Androgen deficiency is usually associated with low luteinizing hormone and follicle-stimulating hormone and is sensitive to the type of measurement of testosterone used. Rates of hypogonadism may be falling since the advent of cART. Causes of low testosterone levels have been attributed to chronic illness, HIV replication, cART, opportunistic infections, comorbidities and coinfections, wasting, and normal age-related declines. Studies of testosterone treatment in HIV-positive men are lacking in standardization and outcome measures. PMID:24466391

Goldmeier, David; Sadeghi-Nejad, Hossein

2014-01-01

403

Markers predicting progression of human immunodeficiency virus-related disease.  

PubMed Central

Human immunodeficiency virus (HIV) interacts with the immune system throughout the course of infection. For most of the disease process, HIV activates the immune system, and the degree of activation can be assessed by measuring serum levels of molecules such as beta 2-microglobulin and neopterin, as well as other serum and cell surface phenotype markers. The levels of some of these markers correlate with clinical progression of HIV disease, and these markers may be useful as surrogate markers for development of clinical AIDS. Because the likelihood and timing of development of clinical AIDS following seroconversion, for any particular individual, are not readily predictable, the use of nonclinical disease markers has become critically important to patient management. Surrogate markers of HIV infection are, by definition, measurable traits that correlate with disease progression. An ideal marker should identify patients at highest risk of disease progression, provide information on how long an individual has been infected, help in staging HIV disease, predict development of opportunistic infections associated with AIDS, monitor the therapeutic efficacy of immunomodulating or antiviral treatments, and the easily quantifiable, reliable, clinically available, and affordable. This review examines the current state of knowledge and the role of surrogate markers in the natural history and treatment of HIV infection. The clinical usefulness of each marker is assessed with respect to the criteria outlined for the ideal surrogate marker for HIV disease progression. PMID:8118788

Tsoukas, C M; Bernard, N F

1994-01-01

404

Hepatitis B and human immunodeficiency virus co-infection  

PubMed Central

Hepatitis B and human immunodeficiency virus (HBV and HIV) infection share transmission patterns and risk factors, which explains high prevalence of chronic HBV infection in HIV infected patients. The natural course of HBV disease is altered by the HIV infection with less chance to clear acute HBV infection, faster progression to cirrhosis and higher risk of liver-related death in HIV-HBV co-infected patients than in HBV mono-infected ones. HIV infected patients with chronic hepatitis B should be counseled for liver damage and surveillance of chronic hepatitis B should be performed to screen early hepatocellular carcinoma. Noninvasive tools are now available to evaluate liver fibrosis. Isolated hepatitis B core antibodies (anti-HBc) are a good predictive marker of occult HBV infection. Still the prevalence and significance of occult HBV infection is controversial, but its screening may be important in the management of antiretroviral therapy. Vaccination against HBV infection is recommended in non-immune HIV patients. The optimal treatment for almost all HIV-HBV co-infected patients should contain tenofovir plus lamivudine or emtricitabine and treatment should not be stopped to avoid HBV reactivation. Long term tenofovir therapy may lead to significant decline in hepatitis B surface Antigen. The emergence of resistant HBV strains may compromise the HBV therapy and vaccine therapy. PMID:25516647

Phung, Bao-Chau; Sogni, Philippe; Launay, Odile

2014-01-01

405

Exercise dysfunction in patients seropositive for the human immunodeficiency virus  

SciTech Connect

To confirm the presence of exercise dysfunction in patients seropositive for the human immunodeficiency virus (HIV), 32 such patients without AIDS were evaluated with cardiopulmonary exercise testing, pulmonary function testing, bronchoalveolar lavage, chest roentgenography, and gallium scanning. No evidence of pulmonary opportunistic infection was found. When compared to an otherwise similar group of HIV-seronegative controls, the patients exercised to a significantly lower workload (195 +/- 30 versus 227 +/- 31 W, p less than 0.001). The ventilatory anaerobic threshold (VAT) values were also significantly lower for the patients (49.2 +/- 13.0 versus 61.9 +/- 9.1% of maximum predicted VO2, p less than 0.001). Nine of the patients had VAT values less than the 95% confidence interval for the controls. This subgroup exercised to a significantly lower maximum VO2 (69.9 +/- 11.2 versus 95.9 +/- 17.5% of maximum predicted VO2, p less than 0.001) and workload (165 +/- 21 versus 227 +/- 31 W) when compared to the control group. These patients demonstrated a mild tachypnea throughout exercise relative to the controls and had a significant increase in the slope of the heart rate to VO2 relationship. These findings are most consistent with a limitation of oxygen delivery to exercising muscles, which may represent occult cardiac disease in this group.

Johnson, J.E.; Anders, G.T.; Blanton, H.M.; Hawkes, C.E.; Bush, B.A.; McAllister, C.K.; Matthews, J.I. (Brooke Army Medical Center, Fort Sam Houston, TX (USA))

1990-03-01

406

Decreased albumin mRNA in immunodeficient wasted' mice  

SciTech Connect

Mice bearing the autosomal recessive gene wst (wst/wst) develop a wasting syndrome' that leads to death by 28-32 days of age. These mice have faulty repair of damage induced by ionizing radiation, immunodeficiency at secretory sites, and neurologic abnormalities. In addition to a progressively more apparent wasted phenotype, wst/wst mice show other features of failure to thrive and malnutrition. Daily body weights of the animals revealed a loss in weight between 25 and 30 days of age, a time during which normal littermates were progressively and rapidly gaining weight. Albumin mRNA levels were measured by dilution dot blot hybridizations of liver-derived RNA preparations from wasted mice, littermates, and parental controls. In all wasted mice, albumin mRNA levels were reduced 5 to 10 fold compared to controls. Northern blots revealed that the albumin mRNA present in wasted mice was normal in length though reduced in amount. These results suggest there may be a relationship between low albumin synthesis and the wasting syndrome of the wst/wst mouse.

Libertin, C.R.; Buczek, N.; Weaver, P.; Mobarhan, S.; Woloschak, G.E. (Loyola Univ. of Chicago, Maywood, IL (United States) Argonne National Lab., IL (United States))

1991-03-15

407

Tuberculosis in patients infected with the human immunodeficiency virus.  

PubMed

A retrospective study of tuberculosis was undertaken among 125 patients infected with human immunodeficiency virus (HIV) who attended our regional infectious disease unit between 1986 and 1989. Nine TB-positive patients (five English, three Africans, one Indian) were identified. In three patients who presented with pyrexia of unknown origin and no objective evidence of any organ involvement, the diagnosis of TB was established from examination of sputum induced by nebulized hypertonic saline. Four other patients had extrapulmonary disease while another two had only pulmonary manifestations of TB. Chest radiographs from five patients were normal, while the other four showed cavities with consolidation, pleural effusion, miliary opacities and hilar enlargement, respectively. All but two mycobacterial isolates were fully sensitive to standard first-line chemotherapeutic drugs. Response to treatment was rapid and only complicated in one patient. There were no relapses following treatment without maintenance therapy after a mean follow-up of 22.2 months (range 9-48). Three patients died, of causes unrelated to TB. Tuberculosis may occur at any stage of HIV disease and is an important cause of fever in HIV-infected British patients, even when chest radiographs are normal and previous BCG vaccination has been performed. PMID:1946941

Ong, E L; Mandal, B K

1991-07-01

408

Diagnostics of Primary Immunodeficiency Diseases: A Sequencing Capture Approach  

PubMed Central

Primary Immunodeficiencies (PID) are genetically inherited disorders characterized by defects of the immune system, leading to increased susceptibility to infection. Due to the variety of clinical symptoms and the complexity of current diagnostic procedures, accurate diagnosis of PID is often difficult in daily clinical practice. Thanks to the advent of “next generation” sequencing technologies and target enrichment methods, the development of multiplex diagnostic assays is now possible. In this study, we applied a selector-based target enrichment assay to detect disease-causing mutations in 179 known PID genes. The usefulness of this assay for molecular diagnosis of PID was investigated by sequencing DNA from 33 patients, 18 of which had at least one known causal mutation at the onset of the experiment. We were able to identify the disease causing mutations in 60% of the investigated patients, indicating that the majority of PID cases could be resolved using a targeted sequencing approach. Causal mutations identified in the unknown patient samples were located in STAT3, IGLL1, RNF168 and PGM3. Based on our results, we propose a stepwise approach for PID diagnostics, involving targeted resequencing, followed by whole transcriptome and/or whole genome sequencing if causative variants are not found in the targeted exons. PMID:25502423

Moens, Lotte N.; Falk-Sörqvist, Elin; Asplund, A. Charlotta; Bernatowska, Ewa; Smith, C. I. Edvard; Nilsson, Mats

2014-01-01

409

Cutaneous manifestations of primary immunodeficiency diseases in children.  

PubMed

Primary immunodeficiency diseases (PIDs) are rare but include severe conditions found predominantly in children, Most PIDs have cutaneous manifestations that may be important as early diagnostic features. The purpose of this study was to determine the frequency and nature of cutaneous alterations associated with PIDs. This article is a cross-sectional study at the department of allergy and clinical immunology of children's medical center conducted between December 5, 2001 and April 20, 2002. The subjects included pediatric patients with a diagnosis of PID and dermatological diagnoses were made by a dermatologist. Two hundred and ten patients were studied They consisted of 68 cases of humoral deficiency, 22 cases of cellular and combined deficiencies, 57 cases of phagocytic defects and 63 cases of other PIDs. In 67 cases (31.8%) the cutaneous alterations preceded and were the basis for clinical immunological diagnosis. Overall cutaneous alterations were infections in 99 cases and eczematous dermatitis in 27 cases. Our findings support the results of other studies that most PIDs have cutaneous features which being their typical aspects are highly suggestive for the diagnosis of PIDs. PMID:17237563

Moin, Athar; Farhoudi, Abolhassan; Moin, Mostafa; Pourpak, Zahra; Bazargan, Nasrin

2006-09-01

410

Comparison of Diagnostic Criteria for Common Variable Immunodeficiency Disorder  

PubMed Central

Common variable immunodeficiency disorders (CVIDs) are the most frequent symptomatic primary immune deficiency condition in adults. The genetic basis for the condition is not known and no single clinical feature or laboratory test can establish the diagnosis; it has been a diagnosis of exclusion. In areas of uncertainty, diagnostic criteria can provide valuable clinical information. Here, we compare the revised European society of immune deficiencies (ESID) registry (2014) criteria with the diagnostic criteria of Ameratunga et al. (2013) and the original ESID/pan American group for immune deficiency (ESID/PAGID 1999) criteria. The ESID/PAGID (1999) criteria either require absent isohemagglutinins or impaired vaccine responses to establish the diagnosis in patients with primary hypogammaglobulinemia. Although commonly encountered, infective and autoimmune sequelae of CVID were not part of the original ESID/PAGID (1999) criteria. Also excluded were a series of characteristic laboratory and histological abnormalities, which are useful when making the diagnosis. The diagnostic criteria of Ameratunga et al. (2013) for CVID are based on these markers. The revised ESID registry (2014) criteria for CVID require the presence of symptoms as well as laboratory abnormalities to establish the diagnosis. Once validated, criteria for CVID will improve diagnostic precision and will result in more equitable and judicious use of intravenous or subcutaneous immunoglobulin therapy. PMID:25309532

Ameratunga, Rohan; Brewerton, Maia; Slade, Charlotte; Jordan, Anthony; Gillis, David; Steele, Richard; Koopmans, Wikke; Woon, See-Tarn

2014-01-01

411

Human immunodeficiency virus, herpes virus infections, and pulmonary vascular disease  

PubMed Central

The following state-of-the-art seminar was delivered as part of the Aspen Lung Conference on Pulmonary Hypertension and Vascular Diseases held in Aspen, Colorado in June 2012. This paper will summarize the lecture and present results from a nonhuman primate model of infection with Simian (Human) Immunodeficiency Virus - nef chimeric virions as well as the idea that polymorphisms in the HIV-1 nef gene may be driving the immune response that results in exuberant inflammation and aberrant endothelial cell (EC) function. We will present data gathered from primary HIV nef isolates where we tested the biological consequences of these polymorphisms and how their presence in human populations may predict patients at risk for developing this disease. In this article, we also discuss how a dysregulated immune system, in conjunction with a viral infection, could contribute to pulmonary arterial hypertension (PAH). Both autoimmune diseases and some viruses are associated with defects in the immune system, primarily in the function of regulatory T cells. These T-cell defects may be a common pathway in the formation of plexiform lesions. Regardless of the route by which viruses may lead to PAH, it is important to recognize their role in this rare disease. PMID:23662195

Flores, Sonia C.; Almodovar, Sharilyn

2013-01-01

412

Common variable immunodeficiency presenting with persistent parvovirus B19 infection.  

PubMed

Parvovirus B19 infection in healthy hosts is self-limited, but persistent infection has been described in patients with cellular immune defects. A 6-year-old boy presented with a 6-month history of weight loss and malaise and a 1-month history of fever and polyarticular arthritis. Parvovirus DNA was detected in plasma at 10 300 copies/mL. Levels of immunoglobulin (Ig)G, IgA, IgM, IgG-1, and IgG-2 were low, and antibody responses to vaccine antigens were impaired. HIV antibody and DNA polymerase chain reaction were negative, and the patient had normal immunophenotype, mitogen stimulation response, CD40 ligand and inducible costimulator expression, transmembrane activator and CAML interactor sequencing, genomic analysis, and fluorescent in situ hybridization for deletions at 22q11.2. Common variable immunodeficiency was diagnosed and replacement therapy with immune globulin intravenous was initiated. The parvovirus DNA level declined by half over 3 months and was undetectable at 15 months. Constitutional symptoms improved but arthritis persisted and eosinophilic fasciitis eventually developed. This case demonstrates that persistent parvovirus infection may be a presenting feature of humoral immune deficiency and can mimic juvenile rheumatoid arthritis. The infection may respond to immune globulin intravenous therapy. PMID:23129076

Adams, Sarah T M; Schmidt, Kara M; Cost, Karen M; Marshall, Gary S

2012-12-01

413

RAG1/2 knockout pigs with severe combined immunodeficiency.  

PubMed

Pigs share many physiological, biochemical, and anatomical similarities with humans and have emerged as valuable large animal models for biomedical research. Considering the advantages in immune system resemblance, suitable size, and longevity for clinical practical and monitoring purpose, SCID pigs bearing dysfunctional RAG could serve as important experimental tools for regenerative medicine, allograft and xenograft transplantation, and reconstitution experiments related to the immune system. In this study, we report the generation and phenotypic characterization of RAG1 and RAG2 knockout pigs using transcription activator-like effector nucleases. Porcine fetal fibroblasts were genetically engineered using transcription activator-like effector nucleases and then used to provide donor nuclei for somatic cell nuclear transfer. We obtained 27 live cloned piglets; among these piglets, 9 were targeted with biallelic mutations in RAG1, 3 were targeted with biallelic mutations in RAG2, and 10 were targeted with a monoallelic mutation in RAG2. Piglets with biallelic mutations in either RAG1 or RAG2 exhibited hypoplasia of immune organs, failed to perform V(D)J rearrangement, and lost mature B and T cells. These immunodeficient RAG1/2 knockout pigs are promising tools for biomedical and translational research. PMID:24973446

Huang, Jiao; Guo, Xiaogang; Fan, Nana; Song, Jun; Zhao, Bentian; Ouyang, Zhen; Liu, Zhaoming; Zhao, Yu; Yan, Quanmei; Yi, Xiaoling; Schambach, Axel; Frampton, Jon; Esteban, Miguel A; Yang, Dongshan; Yang, Huaqiang; Lai, Liangxue

2014-08-01

414

Lipid composition and fluidity of the human immunodeficiency virus.  

PubMed Central

Lipid analyses of the human immunodeficiency virus (HIV) propagated in Hut 78 cells indicated a low total lipid/protein ratio, a high cholesterol/phospholipid molar ratio, and major phospholipids consisting of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and phosphatidylserine; comparable lipid profiles were noted for human erythrocytes and other RNA viruses. Electron spin resonance (ESR) studies of HIV labeled with 5-nitroxide stearate (N-oxy-4',4'-dimethyloxazolidine derivative of ketostearate) showed a low "fluidity" at 37 degrees C, similar to other enveloped RNA viruses and erythrocytes and probably due to the high cholesterol/phospholipid ratio. Ethanol (50%) completely disrupts the envelope, contributing to the rapid inactivation of HIV by ethanol. Contrarily, heating to 57 degrees C causes much less fluidization, and this heating may play a role in the slower viral inactivation at high temperatures. Should a critical minimum ordering in the HIV envelope be necessary for viral stability and infectivity, manipulating the lipid composition or fluidizing the HIV membrane, or both, may provide an untried therapeutic approach. Images PMID:2829209

Aloia, R C; Jensen, F C; Curtain, C C; Mobley, P W; Gordon, L M

1988-01-01

415

Human Immunodeficiency Virus Type 1 Infection of Neural Xenografts  

NASA Astrophysics Data System (ADS)

Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. To study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11 to 17.5 weeks) human fetal brain or neural retina is transplanted to the anterior chamber of the eye of immunosuppressed adult rats. The human xenografts vascularized, formed a blood-brain barrier, and differentiated, forming neurons and glia. The xenografts were infected with cell-free HIV-1 or with HIV-1-infected human monocytes. Analysis by polymerase chain reaction revealed HIV-1 sequences in DNA from xenograft tissue exposed to HIV-1 virions, and in situ hybridization demonstrated HIV-1 mRNA localized in macrophages and multinucleated giant cells. Pathological damage was observed only in neural xenografts containing HIV-1-infected human monocytes, supporting the hypothesis that these cells mediate neurotoxicity. This small animal model allows the study of direct and indirect effects of HIV-1 infection on developing human fetal neural tissues, and it should prove useful in evaluating antiviral therapies, which must ultimately target HIV-1 infection of the brain.

Cvetkovich, Therese A.; Lazar, Eliot; Blumberg, Benjamin M.; Saito, Yoshihiro; Eskin, Thomas A.; Reichman, Richard; Baram, David A.; del Cerro, Coca; Gendelman, Howard E.; del Cerro, Manuel; Epstein, Leon G.

1992-06-01

416

Neutral theory: the stability of forest biodiversity.  

PubMed

The unified neutral theory of biodiversity and biogeography provides a dynamic null hypothesis for the assembly of natural communities. It is also useful for understanding the influence of speciation, extinction, dispersal and ecological drift on patterns of relative species abundance, species-area relationships and phylogeny. Clark and McLachlan argue that neutral drift is inconsistent with the palaeorecord of stability in fossil pollen assemblages of the Holocene forests of southern Canada. We show here that their analysis is based on a partial misunderstanding of neutral theory and that their data alone cannot unambiguously test its validity. PMID:14973471

Volkov, Igor; Banavar, Jayanth R; Maritan, Amos; Hubbell, Stephen P

2004-02-19

417

A shared structural solution for neutralizing ebolaviruses.  

PubMed

Sudan virus (genus Ebolavirus) is lethal, yet no monoclonal antibody is known to neutralize it. We here describe antibody 16F6 that neutralizes Sudan virus and present its structure bound to the trimeric viral glycoprotein. Unexpectedly, the 16F6 epitope overlaps that of KZ52, the only other antibody against the GP(1,2) core to be visualized to date. Furthermore, both antibodies against this crucial epitope bridging GP1-GP2 neutralize at a post-internalization step--probably fusion. PMID:22101933

Dias, João M; Kuehne, Ana I; Abelson, Dafna M; Bale, Shridhar; Wong, Anthony C; Halfmann, Peter; Muhammad, Majidat A; Fusco, Marnie L; Zak, Samantha E; Kang, Eugene; Kawaoka, Yoshihiro; Chandran, Kartik; Dye, John M; Saphire, Erica Ollmann

2011-12-01

418

Intestinal Epithelial Barrier Disruption through Altered Mucosal MicroRNA Expression in Human Immunodeficiency Virus and Simian Immunodeficiency Virus Infections  

PubMed Central

ABSTRACT Epithelial barrier dysfunction during human immunodeficiency virus (HIV) infection has largely been attributed to the rapid and severe depletion of CD4+ T cells in the gastrointestinal (GI) tract. Although it is known that changes in mucosal gene expression contribute to intestinal enteropathy, the role of small noncoding RNAs, specifically microRNA (miRNA), has not been investigated. Using the simian immunodeficiency virus (SIV)-infected nonhuman primate model of HIV pathogenesis, we investigated the effect of viral infection on miRNA expression in intestinal mucosa. SIV infection led to a striking decrease in the expression of mucosal miRNA compared to that in uninfected controls. This decrease coincided with an increase in 5?-3?-exoribonuclease 2 protein and alterations in DICER1 and Argonaute 2 expression. Targets of depleted miRNA belonged to molecular pathways involved in epithelial proliferation, differentiation, and immune response. Decreased expression of several miRNA involved in maintaining epithelial homeostasis in the gut was localized to the proliferative crypt region of the intestinal epithelium. Our findings suggest that SIV-induced decreased expression of miRNA involved in epithelial homeostasis, disrupted expression of miRNA biogenesis machinery, and increased expression of XRN2 are involved in the development of epithelial barrier dysfunction and gastroenteropathy. IMPORTANCE MicroRNA (miRNA) regulate the development and function of intestinal epithelial cells, and many viruses disrupt normal host miRNA expression. In this study, we demonstrate that SIV and HIV disrupt expression of miRNA in the small intestine during infection. The depletion of several key miRNA is localized to the proliferative crypt region of the gut epithelium. These miRNA are known to control expression of genes involved in inflammation, cell death, and epithelial maturation. Our data indicate that this disruption might be caused by altered expression of miRNA biogenesis machinery during infection. These findings suggest that the disruption of miRNA in the small intestine likely plays a role in intestinal enteropathy during HIV infection. PMID:24672033

Gaulke, Christopher A.; Porter, Matthew; Han, Yan-Hong; Sankaran-Walters, Sumathi; Grishina, Irina; George, Michael D.; Dang, Angeline T.; Ding, Shou-Wei; Jiang, Guochun; Korf, Ian

2014-01-01

419

Serial human passage of simian immunodeficiency virus by unsterile injections and the emergence of epidemic human immunodeficiency virus in Africa.  

PubMed

There is compelling evidence that both human immunodeficiency virus (HIV) types emerged from two dissimilar simian immunodeficiency viruses (SIVs) in separate geographical regions of Africa. Each of the two HIVs has its own simian progenitor and specific genetic precursor, and all of the primates that carry these SIVs have been in close contact with humans for thousands of years without the emergence of epidemic HIV. To date no plausible mechanism has been identified to account for the sudden emergence in the mid-20th century of these epidemic HIVs. In this study we examine the conditions needed for SIV to complete the genetic transition from individual human SIV infections to epidemic HIV in humans. The genetic distance from SIV to HIV and the mutational activity needed to achieve this degree of adaptation to human hosts is placed within a mathematical model to estimate the probabilities of SIV completing this transition within a single SIV-infected human host. We found that the emergence of even one epidemic HIV strain, following a single human exposure to SIV, was very unlikely. And the probability of four or more such transitions (i.e. HIV-1 groups M, O and HIV-2 subtypes A and B) occurring in a brief period is vanishingly small. We conclude that SIV cannot become a zoonosis, but requires adaptive mutations to become HIV. Some modern event must have aided in the transition of SIV to HIV. Our research indicates that serial passage of partially adapted SIV between humans could produce the series of cumulative mutations sufficient for the emergence of epidemic HIV strains. We examined the rapid growth of unsterile injections in Africa beginning in the 1950s as a biologically plausible event capable of greatly increasing serial human passage of SIV and generating HIV by a series of multiple genetic transitions. We conclude that increased unsterile injecting in Africa during the period 1950-1970 provided the agent for SIV human infections to emerge as epidemic HIV in the modern era. PMID:11405938

Marx, P A; Alcabes, P G; Drucker, E

2001-06-29

420

47 CFR 64.617 - Neutral Video Communication Service Platform.  

...2014-10-01 2014-10-01 false Neutral Video Communication Service Platform. 64...With Disabilities § 64.617 Neutral Video Communication Service Platform. ...Commission are required to utilize the Neutral Video Communication Service Platform to...

2014-10-01

421

47 CFR 64.617 - Neutral Video Communication Service Platform.  

Code of Federal Regulations, 2013 CFR

...2013-10-01 2013-10-01 false Neutral Video Communication Service Platform. 64...With Disabilities § 64.617 Neutral Video Communication Service Platform. ...Commission are required to utilize the Neutral Video Communication Service Platform to...

2013-10-01

422

Genetics Home Reference: Neutral lipid storage disease with myopathy  

MedlinePLUS

... Recent literature OMIM Genetic disorder catalog Conditions > Neutral lipid storage disease with myopathy On this page: Description ... Glossary definitions Reviewed February 2014 What is neutral lipid storage disease with myopathy? Neutral lipid storage disease ...

423

Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains  

PubMed Central

Rapidly evolving pathogens, such as human immunodeficiency and influenza viruses, escape immune defenses provided by most vaccine-induced antibodies. Proposed strategies to elicit broadly neutralizing antibodies require a deeper understanding of antibody affinity maturation and evolution of the immune response to vaccination or infection. In HIV-infected individuals, viruses and B cells evolve together, creating a virus?antibody “arms race.” Analysis of samples from an individual designated CH505 has illustrated the interplay between an antibody lineage, CH103, and autologous viruses at various time points. The CH103 antibodies, relatively broad in their neutralization spectrum, interact with the CD4 binding site of gp120, with a contact dominated by CDRH3. We show by analyzing structures of progenitor and intermediate antibodies and by correlating them with measurements of binding to various gp120s that there was a shift in the relative orientation of the light- and heavy-chain variable domains during evolution of the CH103 lineage. We further show that mutations leading to this conformational shift probably occurred in response to insertions in variable loop 5 (V5) of the HIV envelope. The shift displaced the tips of the light chain away from contact with V5, making room for the inserted residues, which had allowed escape from neutralization by the progenitor antibody. These results, which document the selective mechanism underlying this example of a virus?antibody arms race, illustrate the functional significance of affinity maturation by mutation outside the complementarity determining region surface of the antibody molecule. PMID:24982157

Fera, Daniela; Schmidt, Aaron G.; Haynes, Barton F.; Gao, Feng; Liao, Hua-Xin; Kepler, Thomas B.; Harrison, Stephen C.

2014-01-01

424

Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains.  

PubMed

Rapidly evolving pathogens, such as human immunodeficiency and influenza viruses, escape immune defenses provided by most vaccine-induced antibodies. Proposed strategies to elicit broadly neutralizing antibodies require a deeper understanding of antibody affinity maturation and evolution of the immune response to vaccination or infection. In HIV-infected individuals, viruses and B cells evolve together, creating a virus-antibody "arms race." Analysis of samples from an individual designated CH505 has illustrated the interplay between an antibody lineage, CH103, and autologous viruses at various time points. The CH103 antibodies, relatively broad in their neutralization spectrum, interact with the CD4 binding site of gp120, with a contact dominated by CDRH3. We show by analyzing structures of progenitor and intermediate antibodies and by correlating them with measurements of binding to various gp120s that there was a shift in the relative orientation of the light- and heavy-chain variable domains during evolution of the CH103 lineage. We further show that mutations leading to this conformational shift probably occurred in response to insertions in variable loop 5 (V5) of the HIV envelope. The shift displaced the tips of the light chain away from contact with V5, making room for the inserted residues, which had allowed escape from neutralization by the progenitor antibody. These results, which document the selective mechanism underlying this example of a virus-antibody arms race, illustrate the functional significance of affinity maturation by mutation outside the complementarity determining region surface of the antibody molecule. PMID:24982157

Fera, Daniela; Schmidt, Aaron G; Haynes, Barton F; Gao, Feng; Liao, Hua-Xin; Kepler, Thomas B; Harrison, Stephen C

2014-07-15

425

Loss of a Conserved N-Linked Glycosylation Site in the Simian Immunodeficiency Virus Envelope Glycoprotein V2 Region Enhances Macrophage Tropism by Increasing CD4-Independent Cell-to-Cell Transmission  

PubMed Central

ABSTRACT Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) strains differ in their capacity to replicate in macrophages, but mechanisms underlying these differences are not fully understood. Here, we identify a highly conserved N-linked glycosylation site (N173 in SIV, corresponding to N160 in HIV) in the V2 region of the SIV envelope glycoprotein (Env) as a novel determinant of macrophage tropism and characterize mechanisms underlying this phenotype. Loss of the N173 glycosylation site in the non-macrophage-tropic SIVmac239 by introducing an N173Q mutation enhanced viral replication and multinucleated giant cell formation upon infection of rhesus macrophages, while the addition of N173 to SIVmac251 had the opposite effect. The removal of N173 in SIVmac239 enhanced CD4-independent cell-to-cell transmission to CCR5-expressing cells. SIVmac239 with N173Q mediated CD4-independent cell-cell fusion but could not infect CD4-negative cells in single-round infections. Thus, CD4-independent phenotypes were detected only in the context of cell-to-cell contact. Similar results were obtained in SIVmac251 with and without N173. N173 decreased the neutralization sensitivity of SIVmac251 but had no effect on the neutralization sensitivity of SIVmac239. The N173Q mutation had no effect on SIVmac239 binding to CD4 in Biacore assays, coimmunoprecipitation assays, and enzyme-linked immunosorbent assays (ELISAs). These findings suggest that the loss of the N173 N-linked glycosylation site increases SIVmac239 replication in macrophages by enhancing CD4-independent cell-to-cell virus transmission through CCR5-mediated fusion. This mechanism may facilitate the escape of macrophage-tropic viruses from neutralizing antibodies while promoting spreading infection by these viruses in vivo. IMPORTANCE In this study, we identify a genetic determinant in the viral envelope (N173) that increases replication and spreading infection of SIV strains in macrophages by enhancing cell-to-cell virus transmission. This effect is explained by a novel mechanism involving increased cell-to-cell fusion in the absence of CD4, the primary receptor that normally mediates virus entry. The same genetic determinant also affects the sensitivity of these viruses to inhibition by neutralizing antibodies. Most macrophage-tropic HIV/SIV strains are known to be neutralization sensitive. Together, these findings suggest that this efficient mode of virus transmission may facilitate the escape of macrophage-tropic viruses from neutralizing antibodies while promoting spreading infection by these viruses to cells expressing little or no CD4 in vivo. PMID:24554659

Yen, Po-Jen; Herschhorn, Alon; Haim, Hillel; Salas, Ignacio; Gu, Christopher; Sodroski, Joseph

2014-01-01

426

An autoneutralizing neutral molecular beam gun  

SciTech Connect

A high-energy (up to 28 keV) neutral molecular beam gun has been developed and put into routine use that takes advantage of the autoneutralization properties of the sulfur hexafluoride anion for the production of high-energy sulfur hexafluoride neutral molecules. The anions are produced in an electron-capture source, accelerated, and focused in a lens assembly designed to minimize residence time, allowed to drift at their terminal velocity for a suitable distance during which up to 30% auto-eject an electron, and all remaining charged particles are electrostatically skimmed, resulting in a focused neutral beam. Rasterable neutral beams focused to a 5-mm spot size up to 3 m from the source have been produced with beam currents up to 40 pA equivalent. Spot sizes of 1 mm can be produced with intensity levels of a few picoamperes equivalent.

Delmore, J.E.; Appelhans, A.D.; Dahl, D.A. (Idaho National Engineering Laboratory, EG G Idaho, Inc., Box 1625, Idaho Falls, Idaho, 83415 (USA))

1990-01-01

427

Ion-Neutral Coupling in Solar Prominence  

NASA Technical Reports Server (NTRS)

Coupling between ions and neutrals in magnetized plasmas is fundamentally important to many aspects of heliophysics, including our ionosphere, the solar chromosphere, the solar wind interaction with planetary atmospheres, and the interface between the heliosphere and the interstellar medium. Ion-neutral coupling also plays a major role in the physics of solar prominences. By combining theory, modeling, and observations we are working toward a better understanding of the structure and dynamics of partially ionized prominence plasma. Two key questions are addressed in the present work: 1) what physical mechanism(s) sets the cross-field scale of prominence threads? 2) Are ion-neutral interactions responsible for the vertical flows and structure in prominences? We present initial results from a study investigating what role ion-neutral interactions play in prominence dynamics and structure. This research was supported by NASA.

Gilbert, H.; DeVore, C. R.; Karpen, J.; Kucera, T.; Antiochos, S.; Kawashima, R.

2011-01-01

428