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1

The consequence of passive administration of an anti-human immunodeficiency virus type 1 neutralizing monoclonal antibody before challenge of chimpanzees with a primary virus isolate.  

PubMed Central

The anti-gp41 virus neutralizing monoclonal antibody 2F5 was infused into chimpanzees, which were then given an intravenous challenge with a primary human immunodeficiency virus type I (HIV-1) isolate. In two control animals, the infection was established immediately, as evidenced by positive cell-associated DNA PCR and serum RNA PCR tests within 1 week, seroconversion by 4 weeks, and development of lymphadenopathy in this acute phase. Serum RNA PCR tests were negative in one of the two antibody-infused animals until week 8 and in the other antibody-infused animal until week 12; both animals seroconverted at week 14. The peak of measurable virus-specific serum RNA was delayed until week 16 in one antibody-infused animal. Virus-specific RNA in the other animal did not reach levels comparable to those in the other animals through 1 year of follow-up studies. Virus was isolated from the week 16 blood sample from one infused animal. Virus was not isolated from peripheral blood of the second animal but was isolated from lymph node cells taken at week 36. The infection of untreated chimpanzees with this primary isolate appears robust. Use of this isolate should widen the scope of possible experiments in the chimpanzee model. This antibody infusion study indicates that neutralizing antibody, when present at the time of challenge, affects the timing and level of infection and remains influential after it can no longer be detected in the peripheral circulation. It is possible that preexisting, neutralizing antibodies (passively administered or actively elicited) affect the course of acute-phase virus replication in humans. It remains to be established whether these immunologically mediated early effects will influence the course of HIV-1 disease. PMID:8794312

Conley, A J; Kessler JA, I I; Boots, L J; McKenna, P M; Schleif, W A; Emini, E A; Mark, G E; Katinger, H; Cobb, E K; Lunceford, S M; Rouse, S R; Murthy, K K

1996-01-01

2

Naphthalene sulfonate polymers with CD4-blocking and anti-human immunodeficiency virus type 1 activities.  

PubMed Central

PIC 024-4 and PRO 2000 are naphthalene sulfonate polymers that bind to CD4 with nanomolar affinity and block binding of gp120. Both have activity against human immunodeficiency virus type 1 in H9 cells, peripheral blood mononuclear cells, and primary monocyte/macrophages, are synergistic with zidovudine, and do not inhibit tetanus toxoid-stimulated T-cell proliferation at anti-human immunodeficiency virus type 1 concentrations. PMID:8787913

Rusconi, S; Moonis, M; Merrill, D P; Pallai, P V; Neidhardt, E A; Singh, S K; Willis, K J; Osburne, M S; Profy, A T; Jenson, J C; Hirsch, M S

1996-01-01

3

Anti-Human Immunodeficiency Virus Type 1 (HIV-1) Antibodies 2F5 and 4E10 Require Surprisingly Few Crucial Residues in the Membrane-Proximal External Region of Glycoprotein gp41 To Neutralize HIV-1  

PubMed Central

The conserved membrane-proximal external region (MPER) of human immunodeficiency virus type 1 (HIV-1) gp41 is a target of two broadly neutralizing human monoclonal antibodies, 2F5 and 4E10, and is an important lead for vaccine design. However, immunogens that bear MPER epitopes so far have not elicited neutralizing antibodies in laboratory animals. One explanation is that the immunogens fail to recreate the proper molecular environment in which the epitopes of 2F5 and 4E10 are presented on the virus. To explore this molecular environment, we used alanine-scanning mutagenesis across residues 660 to 680 in the MPER of a pseudotyped variant of HIV-1JR-FL, designated HIV-1JR2, and examined the ability of 2F5 and 4E10 to neutralize the Ala mutant viruses. The results show that the only changes to produce neutralization resistance to 2F5 occurred in residue D, K, or W of the core epitope (LELDKWANL). Likewise, 4E10 resistance arose by replacing one of three residues; two (W and F) were in the core epitope, and one (W) was seven residues C-terminal to these two (NWFDISNWLW). Importantly, no single substitution resulted in resistance of virus to both 2F5 and 4E10. Surprisingly, 8 out of 21 MPER Ala mutants were more sensitive than the parental pseudovirus to 2F5 and/or 4E10. At most, only small differences in neutralization sensitivity to anti-gp120 monoclonal antibody b12 and peptide T20 were observed with the MPER Ala mutant pseudoviruses. These data suggest that MPER substitutions can act locally and enhance the neutralizing activity of antibodies to this region and imply a distinct role of the MPER of gp41 during HIV-1 envelope-mediated fusion. Neutralization experiments showing synergy between and T20 and 4E10 against HIV-1 are also presented. The data presented may aid in the design of antigens that better present the MPER of gp41 to the immune system. PMID:15613352

Zwick, Michael B.; Jensen, Richard; Church, Sarah; Wang, Meng; Stiegler, Gabriela; Kunert, Renate; Katinger, Hermann; Burton, Dennis R.

2005-01-01

4

Intracellular Metabolism of the Nucleotide Prodrug GS9131, a Potent Anti-Human Immunodeficiency Virus Agent  

Microsoft Academic Search

GS-9131 is a phosphonoamidate prodrug of the novel ribose-modified phosphonate nucleotide analog GS-9148 that demonstrates potent anti-human immunodeficiency virus type 1 (HIV-1) activity and an excellent resistance profile in vitro. Prodrug moieties were optimized for the efficient delivery of GS-9148 and its active diphosphate (DP) metabolite to lymphoid cells following oral administration. To understand the intracellular pharmacology of GS-9131, incubations

Adrian S. Ray; Jennifer E. Vela; Constantine G. Boojamra; Lijun Zhang; Hon Hui; Christian Callebaut; Kirsten Stray; Kuei-Ying Lin; Ying Gao; Richard L. Mackman; Tomas Cihlar

2008-01-01

5

Induction of murine mucosal CCR5-reactive antibodies as an anti-human immunodeficiency virus strategy  

Microsoft Academic Search

The genital mucosa is the main site of initial human immunodeficiency virus type 1 (HIV-1) contact with its host. In spite of repeated sexual exposure, some individuals remain seronegative, and a small fraction of them produce immunoglobulin G (IgG) and IgA autoantibodies directed against CCR5, which is probably the cause of the CCR5-minus phenotype observed in the peripheral blood mononuclear

C. Barassi; E. Soprana; C. Pastori; R. Longhi; E. Buratti; F. Lillo; C. Marenzi; A. Lazzarin; A. G. Siccardi; L. Lopalco

2005-01-01

6

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

7

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

8

Preclinical Safety Assessments of UC781 Anti-Human Immunodeficiency Virus Topical Microbicide Formulations?  

PubMed Central

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.

2007-01-01

9

Ontogeny of anti-human immunodeficiency virus (HIV) antibody production in HIV-1-infected infants.  

PubMed Central

The early serologic response of infants to infection with human immunodeficiency virus type 1 (HIV-1) is normally obscured by the presence of transplacentally acquired maternal HIV antibody. By measuring HIV antibody produced in vitro by lymphocytes isolated from peripheral blood of infants and children of HIV-1-infected mothers, we have been able to study the natural acquisition of humoral immunity to perinatal HIV-1 infection. One hundred ninety-seven infants of HIV-1-infected women were studied prospectively and longitudinally from birth. In the neonatal period, infected infants produced only small amounts of HIV-specific IgG antibodies to a restricted number of antigens. The amount of immunoglobulin to HIV-1 and the number of HIV-1 antigens recognized increased with age. After 6 months of life 85% of infected infants made detectable antibody to two or more viral proteins. Antibody to gp160 appeared first and was the most frequently found at all ages, followed by antibody to the envelope proteins gp120 and gp41. The amount of HIV antibody produced correlated positively with the percentage of CD4+ T lymphocytes in peripheral blood. This assay provides a method of studying the immunogenicity of vaccines against HIV-1 in HIV-1-infected infants and of assessing the effect of early therapeutic interventions on the humoral response to HIV-1. PMID:8460144

Pollack, H; Zhan, M X; Ilmet-Moore, T; Ajuang-Simbiri, K; Krasinski, K; Borkowsky, W

1993-01-01

10

Unique intracellular activation of the potent anti-human immunodeficiency virus agent 1592U89.  

PubMed Central

The anabolism of 1592U89, (-)-(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclo pentene-1-methanol, a selective inhibitor of human immunodeficiency virus (HIV), was characterized in human T-lymphoblastoid CD4+ CEM cells. 1592U89 was ultimately anabolized to the triphosphate (TP) of the guanine analog (-)-carbovir (CBV), a potent inhibitor of HIV reverse transcriptase. However, less than 2% of intracellular 1592U89 was converted to CBV, an amount insufficient to account for the CBV-TP levels observed. 1592U89 was anabolized to its 5'-monophosphate (MP) by the recently characterized enzyme adenosine phosphotransferase, but neither its diphosphate (DP) nor its TP was detected. The MP, DP, and TP of CBV were found in cells incubated with either 1592U89 or CBV, with CBV-TP being the major phosphorylated species. We confirmed that CBV is phosphorylated by 5'-nucleotidase and that mycophenolic acid increased the formation of CBV-TP from CBV 75-fold. However, mycophenolic acid did not stimulate 1592U89 anabolism to CBV-TP. The adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) did not inhibit CBV-TP formation from CBV or 1592U89, whereas the adenylate deaminase inhibitor 2'-deoxycoformycin selectively inhibited 1592U89 anabolism to CBV-TP and reversed the antiviral activity of 1592U89. 1592U89-MP was not a substrate for adenylate deaminase but was a substrate for a distinct cytosolic deaminase that was inhibited by 2'-deoxycoformycin-5'-MP. Thus, 1592U89 is phosphorylated by adenosine phosphotransferase to 1592U89-MP, which is converted by a novel cytosolic enzyme to CBV-MP. CBV-MP is then further phosphorylated to CBV-TP by cellular kinases. This unique activation pathway enables 1592U89 to overcome the pharmacokinetic and toxicological deficiencies of CBV while maintaining potent and selective anti-HIV activity. PMID:9145876

Faletto, M B; Miller, W H; Garvey, E P; St Clair, M H; Daluge, S M; Good, S S

1997-01-01

11

Anti-human immunodeficiency virus type 1 antibody complexes on platelets of seropositive thrombocytopenic homosexuals and narcotic addicts.  

PubMed Central

Patients with human immunodeficiency virus type 1 (HIV-1) infection develop an immunologic thrombocytopenic purpura associated with markedly elevated platelet IgG, IgM, and C3C4 as well as serum immune complexes determined by the polyethylene glycol (PEG) method. Analysis of their serum PEG-precipitable immune complexes as well as platelet acid eluates revealed the presence of anti-HIV-1 antibody existing as a complex that eluted in the void volume of a Sephadex G-200 gel-filtration column. The complex binds to washed normal platelets, whereas affinity-purified anti-HIV-1 (gp120) antibody does not. HIV-1 antigen or proviral DNA was not detectable in the immune complexes or platelet extracts. However, anti-antibodies directed against anti-HIV-1 antibody were detectable in the immune complexes as well as platelet eluates. Approximately 50% of eluted platelet IgG contained anti-HIV-1 antibody. Thus the markedly elevated platelet immunoglobulin is partly due to the presence of anti-HIV-1 antibody complexes. This may be responsible for the enhanced platelet clearance and thrombocytopenia in patients with acquired immunodeficiency syndrome-related immunologic thrombocytopenia. Images PMID:3200854

Karpatkin, S; Nardi, M; Lennette, E T; Byrne, B; Poiesz, B

1988-01-01

12

Suppression of the modulatory effects of the antileukemic and anti-human immunodeficiency virus compound avarol on gene expression by tryptophan.  

PubMed

The amino acid L-tryptophan is known to be a modulator of many processes of cell metabolism. In this contribution we show that L-tryptophan interferes with some biological effects of the antileukemic and anti-human immunodeficiency virus agent avarol, possibly by different mechanisms. Avarol has been shown to be able to modulate posttranscriptional events of mRNA synthesis, resulting in an increase of the base-sequence complexities of the nonabundant and rare mRNA classes. Here it is demonstrated that this change in mRNA abundancy distribution is accompanied by an increase in the level of some specific, low abundant mRNAs (ras and c-myc). Addition of L-tryptophan was found to abolish avarol-caused gene relaxation in L1210 mouse leukemia cells. In addition, L-tryptophan suppressed the induction of gamma-interferon mRNA production in human peripheral blood lymphocytes. At the level of DNA, L-tryptophan inhibited the production of strand breaks by cytotoxic avarol concentrations in Friend erythroleukemia cells in vitro. Moreover, it competed with avarol for binding to the nuclear envelope binding site; this effect was not shown by other amino acids. PMID:2495175

Schröder, H C; Wenger, R; Gerner, H; Reuter, P; Kuchino, Y; Sladi?, D; Müller, W E

1989-04-15

13

Broadly Neutralizing Antibodies Targeted to the Membrane-Proximal External Region of Human Immunodeficiency Virus Type 1 Glycoprotein gp41  

PubMed Central

The identification and epitope mapping of broadly neutralizing anti-human immunodeficiency virus type 1 (HIV-1) antibodies (Abs) is important for vaccine design, but, despite much effort, very few such Abs have been forthcoming. Only one broadly neutralizing anti-gp41 monoclonal Ab (MAb), 2F5, has been described. Here we report on two MAbs that recognize a region immediately C-terminal of the 2F5 epitope. Both MAbs were generated from HIV-1-seropositive donors, one (Z13) from an antibody phage display library, and one (4E10) as a hybridoma. Both MAbs recognize a predominantly linear and relatively conserved epitope, compete with each other for binding to synthetic peptide derived from gp41, and bind to HIV-1MN virions. By flow cytometry, these MAbs appear to bind relatively weakly to infected cells and this binding is not perturbed by pretreatment of the infected cells with soluble CD4. Despite the apparent linear nature of the epitopes of Z13 and 4E10, denaturation of recombinant envelope protein reduces the binding of these MAbs, suggesting some conformational requirements for full epitope expression. Most significantly, Z13 and 4E10 are able to neutralize selected primary isolates from diverse subtypes of HIV-1 (e.g., subtypes B, C, and E). The results suggest that a rather extensive region of gp41 close to the transmembrane domain is accessible to neutralizing Abs and could form a useful target for vaccine design. PMID:11602729

Zwick, Michael B.; Labrijn, Aran F.; Wang, Meng; Spenlehauer, Catherine; Saphire, Erica Ollmann; Binley, James M.; Moore, John P.; Stiegler, Gabriela; Katinger, Hermann; Burton, Dennis R.; Parren, Paul W. H. I.

2001-01-01

14

Characterization of a human immunodeficiency virus neutralizing monoclonal antibody and mapping of the neutralizing epitope.  

PubMed Central

A monoclonal antibody was produced to the exterior envelope glycoprotein (gp120) of the human T-cell lymphotropic virus (HTLV)-IIIB isolate of the human immunodeficiency virus (HIV). This antibody binds to gp120 of HTLV-IIIB and lymphadenopathy-associated virus type 1 (LAV-1) and to the surface of HTLV-IIIB- and LAV-1-infected cells, neutralizes infection by cell-free virus, and prevents fusion of virus-infected cells. In contrast, it does not bind, or weakly binds, the envelope of four heterologous HIV isolates and does not neutralize heterologous isolates HTLV-IIIRF and HTLV-IIIMN. The antibody-binding site was mapped to a 24-amino-acid segment, using recombinant and synthetic segments of HTLV-IIIB gp120. This site is within a segment of amino acid variability known to contain the major neutralizing epitopes (S. D. Putney, T. J. Matthews, W. G. Robey, D. L. Lynn, M. Robert-Guroff, W. T. Mueller, A. J. Langlois, J. Ghrayeb, S. R. Petteway, K. J. Weinhold, P. J. Fischinger, F. Wong-Staal, R. C. Gallo, and D. P. Bolognesi, Science 234:1392-1395, 1986). These results localize an epitope of HIV type-specific neutralization and suggest that neutralizing antibodies may be effective in controlling cell-associated, as well as cell-free, virus infection. Images PMID:2452899

Matsushita, S; Robert-Guroff, M; Rusche, J; Koito, A; Hattori, T; Hoshino, H; Javaherian, K; Takatsuki, K; Putney, S

1988-01-01

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

Chimpanzees Immunized with Recombinant Soluble CD4 Develop Anti-Self CD4 Antibody Responses with Anti-Human Immunodeficiency Virus Activity  

NASA Astrophysics Data System (ADS)

In view of the efficiency with which human immunodeficiency virus replication can be blocked in vitro with anti-CD4 antibodies, the elicitation of an anti-CD4 antibody response through active immunization might represent a useful therapeutic strategy for AIDS. Here we demonstrate that immunization of chimpanzees with recombinant soluble human CD4 elicited an anti-CD4 antibody response. The elicited antibody bound self CD4 on digitonin-treated but not freshly isolated lymphocytes. Nevertheless, this antibody blocked human immunodeficiency virus replication in chimpanzee and human lymphocytes. These observations suggest that immunization with recombinant soluble CD4 from human immunodeficiency virus-infected humans may be feasible and therapeutically beneficial.

Watanabe, Mamoru; Boyson, Jonathan E.; Lord, Carol I.; Letvin, Norman L.

1992-06-01

17

A Tight-Binding Mode of Inhibition Is Essential for Anti-Human Immunodeficiency Virus Type 1 Virucidal Activity of Nonnucleoside Reverse Transcriptase Inhibitors  

Microsoft Academic Search

It was previously found that certain nonnucleoside reverse transcriptase inhibitors (NNRTI) possess viru- cidal activity against human immunodeficiency virus type 1 (HIV-1), and it was suggested that the tight- binding mode of inhibition of reverse transcriptase might be important for this virucidal activity (Borkow et al., J. Virol. 71:3023-3030, 1997). To test this, we compared six different NNRTI, including three

Dimitrios Motakis; Michael A. Parniak

2002-01-01

18

How Accurate is Serologic Testing of Plasma Pools for Hepatitis B Virus Surface Antigen, anti-Human Immunodeficiency Virus 1 and 2, and anti-Hepatitis C Virus?  

Microsoft Academic Search

SummaryObjective: The European pharmacopeia prescribes that, during the manufacture of blood derivates, the first homogeneous pool of plasma (for example, after removal of cryoprecipitate) must be tested for hepatitis B virus surface antigen (HBsAg), for hepatitis C virus (HCV) antibodies and for human immunodeficiency virus (HIV) antibodies using test methods of suitable sensitivity and specificity, in order to reduce the

H. Rabenau; R. Schütz; A. Berger; H. W. Doerr; B. Weber

1996-01-01

19

Crystal Structure and Structural Mechanism of a Novel Anti-Human Immunodeficiency Virus and D-Amino AcidContaining Chemokine  

Microsoft Academic Search

Chemokines and their receptors play important roles in normal physiological functions and the pathogeneses of a wide range of human diseases, including the entry of human immunodeficiency virus type 1 (HIV-1). However, the use of natural chemokines to probe receptor biology or to develop therapeutic drugs is limited by their lack of selectivity and the poor understanding of mechanisms in

Dongxiang Liu; Navid Madani; Ying Li; Rong Cao; Won-Tak Choi; Sameer P. Kawatkar; Mi Youn Lim; Santosh Kumar; Chang-Zhi Dong; Jun Wang; Julie D. Russell; Caroline R. Lefebure; Jing An; Scott Wilson; Yi-Gui Gao; Luke A. Pallansch; Joseph G. Sodroski; Ziwei Huang

2007-01-01

20

Neutralizing Antibodies in Sera from Macaques Immunized with Attenuated Simian Immunodeficiency Virus  

Microsoft Academic Search

Infection with attenuated simian immunodeficiency virus (SIV) in rhesus macaques has been shown to raise antibodies capable of neutralizing an animal challenge stock of primary SIVmac251 in CEMx174 cells that cor- relate with resistance to infection after experimental challenge with this virulent virus (M. S. Wyand, K. H. Man- son, M. Garcia-Moll, D. C. Montefiori, and R. C. Desrosiers, J.

ALPHONSE J. LANGLOIS; RONALD C. DESROSIERS; MARK G. LEWIS; VINEET N. KEWALRAMANI; DAN R. LITTMAN; JI YING ZHOU; KELLEDY MANSON; MICHAEL S. WYAND; DANI P. BOLOGNESI; DAVID C. MONTEFIORI

1998-01-01

21

ARG098, a novel anti-human Fas antibody, suppresses synovial hyperplasia and prevents cartilage destruction in a severe combined immunodeficient-HuRAg mouse model  

PubMed Central

Background The anti-human Fas/APO-1/CD95 (Fas) mouse/human chimeric monoclonal IgM antibody ARG098 (ARG098) targets the human Fas molecule. The cytotoxic effects of ARG098 on cells isolated from RA patients, on normal cells in vitro, and on RA synovial tissue and cartilage in vivo using implanted rheumatoid tissues in an SCID mouse model (SCID-HuRAg) were investigated to examine the potential of ARG098 as a therapy for RA. Methods ARG098 binding to each cell was analyzed by cytometry. The effects of ARG098 on several cells were assessed by a cell viability assay in vitro. Effects on the RA synovium, lymphocytes, and cartilage were assessed in vivo using the SCID-HuRAg mouse model. Results ARG098 bound to cell surface Fas molecules, and induced apoptosis in Fas-expressing RA synoviocytes and infiltrating lymphocytes in the RA synovium in a dose-dependent manner. However, ARG098 did not affect the cell viability of peripheral blood mononuclear cells of RA patients or normal chondrocytes. ARG098 also induced apoptosis in RA synoviocytes and infiltrating lymphocytes in the RA synovium in vivo. The destruction of cartilage due to synovial invasion was inhibited by ARG098 injection in the modified SCID-HuRAg mouse model. Conclusions ARG098 treatment suppressed RA synovial hyperplasia through the induction of apoptosis and prevented cartilage destruction in vivo. These results suggest that ARG098 might become a new therapy for RA. PMID:20875116

2010-01-01

22

Cross-reactivity of anti-human immunodeficiency virus type 1 gp41 antibodies with human astrocytes and astrocytoma cell lines.  

PubMed Central

An antigen expressed by astrocytes in human brain tissue and by various human astrocytoma cell lines was shown to cross-react with a monoclonal antibody generated against amino acids (aa) 584 to 609 of the transmembrane protein gp41 of human immunodeficiency virus type 1 (HIV-1). This region is an immunodominant segment of gp41, and high levels of antibodies against this epitope have been detected in both serum and cerebrospinal fluid of HIV-infected individuals at all stages of HIV infection. Immunohistochemistry with this monoclonal antibody demonstrated the presence of a cross-reactive antigen in human brain tissue, with an increased frequency and intensity of staining in HIV-positive individuals when compared with HIV-negative controls. By using a panel of HIV-positive and -negative sera, we show that antibodies in HIV-positive serum specifically bound to the surfaces of human astrocytoma cells. HIV-positive sera depleted of antibodies recognizing gp41 aa 584 to 609 showed a significant diminution in cell surface binding. Conversely, the serum antibodies that bound to and were eluted from the aa 584 to 609 peptide also bound to the astrocyte cell surface. To identify the target antigen, the immunoreactivity of three astrocytoma cell lines was examined. By immunoprecipitation of metabolically labeled cell lysates and Western blot (immunoblot) analysis, we identified a protein of approximately 100 kDa as the target antigen. Cross-reactive antibodies between HIV proteins and astrocyte epitopes, such as this 100-kDa protein and others previously reported, suggests that an autoimmune response against these target antigens may disrupt the normal functions of astrocytes. Images PMID:8083966

Spehar, T; Strand, M

1994-01-01

23

Analysis of Neutralization Specificities in Polyclonal Sera Derived from Human Immunodeficiency Virus Type 1-Infected Individuals? †  

PubMed Central

During human immunodeficiency virus type 1 (HIV-1) infection, patients develop various levels of neutralizing antibody (NAb) responses. In some cases, patient sera can potently neutralize diverse strains of HIV-1, but the antibody specificities that mediate this broad neutralization are not known, and their elucidation remains a formidable challenge. Due to variable and nonneutralizing determinants on the exterior envelope glycoprotein (Env), nonnative Env protein released from cells, and the glycan shielding that assembles in the context of the quaternary structure of the functional spike, HIV-1 Env elicits a myriad of binding antibodies. However, few of these antibodies can neutralize circulating viruses. We present a systematic analysis of the NAb specificities of a panel of HIV-1-positive sera, using methodologies that identify both conformational and continuous neutralization determinants on the HIV-1 Env protein. Characterization of sera included selective adsorption with native gp120 and specific point mutant variants, chimeric virus analysis, and peptide inhibition of viral neutralization. The gp120 protein was the major neutralizing determinant for most sera, although not all neutralization activity against all viruses could be identified. In some broadly neutralizing sera, the gp120-directed neutralization mapped to the CD4 binding region of gp120. In addition, we found evidence that regions of the gp120 coreceptor binding site may also be a target of neutralizing activity. Sera displaying limited neutralization breadth were mapped to the immunogenic V3 region of gp120. In a subset of sera, we also identified NAbs directed against the conserved, membrane-proximal external region of gp41. These data allow a more detailed understanding of the humoral responses to the HIV-1 Env protein and provide insights regarding the most relevant targets for HIV-1 vaccine design. PMID:19004942

Li, Yuxing; Svehla, Krisha; Louder, Mark K.; Wycuff, Diane; Phogat, Sanjay; Tang, Min; Migueles, Stephen A.; Wu, Xueling; Phogat, Adhuna; Shaw, George M.; Connors, Mark; Hoxie, James; Mascola, John R.; Wyatt, Richard

2009-01-01

24

Feline immunodeficiency virus (FIV) vaccine efficacy and FIV neutralizing antibodies.  

PubMed

A HIV-1 tier system has been developed to categorize the various subtype viruses based on their sensitivity to vaccine-induced neutralizing antibodies (NAbs): tier 1 with greatest sensitivity, tier 2 being moderately sensitive, and tier 3 being the least sensitive to NAbs (Mascola et al., J Virol 2005; 79:10103-7). Here, we define an FIV tier system using two related FIV dual-subtype (A+D) vaccines: the commercially available inactivated infected-cell vaccine (Fel-O-Vax(®) FIV) and its prototype vaccine solely composed of inactivated whole viruses. Both vaccines afforded combined protection rates of 100% against subtype-A tier-1 FIVPet, 89% against subtype-B tier-3 FIVFC1, 61% against recombinant subtype-A/B tier-2 FIVBang, 62% against recombinant subtype-F'/C tier-3 FIVNZ1, and 40% against subtype-A tier-2 FIVUK8 in short-duration (37-41 weeks) studies. In long-duration (76-80 weeks) studies, the commercial vaccine afforded a combined protection rate of at least 46% against the tier-2 and tier-3 viruses. Notably, protection rates observed here are far better than recently reported HIV-1 vaccine trials (Sanou et al., The Open AIDS J 2012; 6:246-60). Prototype vaccine protection against two tier-3 and one tier-2 viruses was more effective than commercial vaccine. Such protection did not correlate with the presence of vaccine-induced NAbs to challenge viruses. This is the first large-scale (228 laboratory cats) study characterizing short- and long-duration efficacies of dual-subtype FIV vaccines against heterologous subtype and recombinant viruses, as well as FIV tiers based on in vitro NAb analysis and in vivo passive-transfer studies. These studies demonstrate that not all vaccine protection is mediated by vaccine-induced NAbs. PMID:23800540

Coleman, James K; Pu, Ruiyu; Martin, Marcus M; Noon-Song, Ezra N; Zwijnenberg, Raphael; Yamamoto, Janet K

2014-02-01

25

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

26

Regional Clustering of Shared Neutralization Determinants on Primary Isolates of Clade C Human Immunodeficiency Virus Type 1 from South Africa  

Microsoft Academic Search

Clade C is one of the most prevalent genetic subtypes of human immunodeficiency virus type 1 (HIV-1) in the world today and one of the least studied with respect to neutralizing antibodies. Most information on HIV-1 serology as it relates to neutralization is derived from clade B. Clade C primary isolates of HIV-1 from South Africa and Malawi were shown

Renata Bures; Lynn Morris; Carolyn Williamson; Gita Ramjee; Mark Deers; Susan A. Fiscus; Salim Abdool-Karim; David C. Montefiori

2002-01-01

27

Neutralizing antibodies in sera from macaques immunized with attenuated simian immunodeficiency virus.  

PubMed

Infection with attenuated simian immunodeficiency virus (SIV) in rhesus macaques has been shown to raise antibodies capable of neutralizing an animal challenge stock of primary SIVmac251 in CEMx174 cells that correlate with resistance to infection after experimental challenge with this virulent virus (M. S. Wyand, K. H. Manson, M. Garcia-Moll, D. C. Montefiori, and R. C. Desrosiers, J. Virol. 70:3724-3733, 1996). Here we show that these neutralizing antibodies are not detected in human and rhesus peripheral blood mononuclear cells (PBMC). In addition, neutralization of primary SIVmac251 in human and rhesus PBMC was rarely detected with plasma samples from a similar group of animals that had been infected either with SIVmac239Deltanef for 1.5 years or with SIVmac239Delta3 for 3.2 years, although low-level neutralization was detected in CEMx174 cells. Potent neutralization was detected in CEMx174 cells when the latter plasma samples were assessed with laboratory-adapted SIVmac251. In contrast to primary SIVmac251, laboratory-adapted SIVmac251 did not replicate in human and rhesus PBMC despite its ability to utilize CCR5, Bonzo/STRL33, and BOB/gpr15 as coreceptors for virus entry. These results illustrate the importance of virus passage history and the choice of indicator cells for making assessments of neutralizing antibodies to lentiviruses such as SIV. They also demonstrate that primary SIVmac251 is less sensitive to neutralization in human and rhesus PBMC than it is in established cell lines. Results obtained in PBMC did not support a role for neutralizing antibodies as a mechanism of protection in animals immunized with attenuated SIV and challenged with primary SIVmac251. PMID:9658152

Langlois, A J; Desrosiers, R C; Lewis, M G; KewalRamani, V N; Littman, D R; Zhou, J Y; Manson, K; Wyand, M S; Bolognesi, D P; Montefiori, D C

1998-08-01

28

Immunodeficiency \\  

Microsoft Academic Search

For the last 50 years immune deficiency disorders were thought to be rare occurring in one out of thousands of infants. Indeed in the last 10 years with the development of new genetic techniques more than 100 mutations in various genes were found to be associated with pri- mary immunodeficiencies entities. It should be noted that in some diseases several

Amos Etzioni

29

Time Frames for Neutralization during the Human Immunodeficiency Virus Type 1 Entry Phase, as Monitored in Synchronously Infected Cell Cultures  

Microsoft Academic Search

Characterization of the neutralizing interaction between antibody and virus is hindered by the nonsynchro- nized progression of infection in cell cultures. Discrete steps of the viral entry sequence cannot be discerned, and thus, the mode of antibody-mediated interference with virus infectivity remains undefined. Here, we magnetically synchronize the motion and cell attachment of human immunodeficiency virus type 1 (HIV-1) to

Hillel Haim; Israel Steiner; Amos Panet

2007-01-01

30

An Envelope Modification That Renders a Primary, Neutralization Resistant Clade B Human Immunodeficiency Virus Type 1 Isolate Highly Susceptible to Neutralization by Sera from Other Clades  

Microsoft Academic Search

SF162 is a primary (PR), non-syncytium-inducing, macrophagetropic human immunodeficiency virus type 1 (HIV-1) clade B isolate which is resistant to antibody-mediated neutralization. Deletion of the first or second hypervariable envelope gp120 region (V1 or V2 loop, respectively) of this virus does not abrogate its ability to replicate in peripheral blood mononuclear cells and primary macrophages, nor does it alter its

LEONIDAS STAMATATOS; CECILIA CHENG-MAYER

1998-01-01

31

Synergistic neutralization of human immunodeficiency virus type 1 by combinations of human monoclonal antibodies.  

PubMed Central

The ability of antibodies to the V3 region and the CD4-binding domain (CD4bd) of human immunodeficiency virus type 1 (HIV-1) to act in synergy to neutralize HIV has been demonstrated previously. However, synergy between antibodies to other HIV-1 epitopes has not been studied. We have used 21 combinations of human monoclonal antibodies (MAbs) directed against different epitopes of the gp120 and gp41 proteins of HIV-1 to evaluate their ability to act in synergy to neutralize HIV-1. Combinations of anti-V3 and anti-CD4bd antibodies, anti-V3 and anti-gp120 C-terminus antibodies, anti-CD4bd and anti-C-terminus antibodies, anti-V3 and anti-gp41 antibodies, and anti-CD4bd and anti-gp41 antibodies were tested. Our results show that some, but not all anti-V3 antibodies can act in synergy with anti-CD4bd antibodies. In addition, for the first time, antibodies to the C-terminus region have been found to act in synergy with the anti-CD4bd antibodies. Various anti-CD4bd MAbs also act in synergy when used together. The use of such cocktails of human MAbs for passive immunization against HIV-1 may prove to be important for therapy in postexposure settings and for prevention of maternal-fetal transmission of the virus. The results also provide information on the types of antibodies that should be elicited by an effective vaccine. PMID:7514683

Laal, S; Burda, S; Gorny, M K; Karwowska, S; Buchbinder, A; Zolla-Pazner, S

1994-01-01

32

CD4 Independence of Simian Immunodeficiency Virus Envs Is Associated with Macrophage Tropism, Neutralization Sensitivity, and Attenuated Pathogenicity  

Microsoft Academic Search

To investigate the basis for envelope (Env) determinants influencing simian immunodeficiency virus (SIV) tropism, we studied a number of Envs that are closely related to that of SIVmac239, a pathogenic, T-tropic virus that is neutralization resistant. The Envs from macrophage-tropic (M-tropic) virus strains SIVmac316, 1A11, 17E-Fr, and 1100 facilitated infection of CCR5-positive, CD4-negative cells. In contrast, the SIVmac239 Env was

Bridget A. Puffer; Stefan Pöhlmann; Aimee L. Edinger; Dan Carlin; Melissa D. Sanchez; Julie Reitter; Debbie D. Watry; Howard S. Fox; Ronald C. Desrosiers; Robert W. Doms

2002-01-01

33

Neutralizing Antibody Responses against Autologous and Heterologous Viruses in Acute versus Chronic Human Immunodeficiency Virus (HIV) Infection: Evidence for a Constraint on the Ability of HIV To Completely Evade Neutralizing Antibody Responses  

Microsoft Academic Search

Acute human immunodeficiency virus (HIV) infection is associated with the rapid development of neutral- ization escape mutations. The degree to which viral evolution persists in chronic infection has not been well characterized, nor is it clear if all patients develop high-level neutralization antibody escape. We therefore measured neutralizing antibody responses against autologous and heterologous viruses in a cohort of acutely

Steven G. Deeks; Becky Schweighardt; Terri Wrin; Justin Galovich; Rebecca Hoh; Elizabeth Sinclair; Peter Hunt; Joseph M. McCune; Jeffrey N. Martin; Christos J. Petropoulos; Frederick M. Hecht

2006-01-01

34

Immunodeficiencies  

PubMed Central

Primary immunodeficiencies (PIDs) are uncommon, chronic and severe disorders of the immune system in which patients cannot mount a sufficiently protective immune response, leading to an increased susceptibility to infections. The treatment of choice for PID patients with predominant antibody deficiency is intravenous immunoglobulin (Ig) replacement therapy. Despite major advances over the last 20 years in the molecular characterization of PIDs, many patients remain undiagnosed or are diagnosed too late, with severe consequences. Various strategies to ensure timely diagnosis of PIDs are in place, and novel approaches are being developed. In recent years, several patient registries have been established. Such registries shed light on the pathology and natural history of these varied disorders. Analyses of the registry data may also reveal which patients are likely to respond well to higher Ig infusion rates and may help to determine the optimal dosing of Ig products. Faster infusion rates may lead to improved convenience for patients and thus increase patient compliance, and may reduce nursing time and the need for hospital resources. Data from two recent studies suggest that Gamunex® and Privigen® are well tolerated at high infusion rates. Nevertheless, careful selection of patients for high infusion rates, based on co-morbid conditions and tolerance of the current infusion rate, is advisable. Based on the available data, intravenous Ig offers broad protection against encapsulated organisms. As vaccine trends change, careful monitoring of specific antibody levels in the general population, such as those against pneumococcal and meningococcal bacteria, should be implemented. PMID:19883420

Ballow, M; Notarangelo, L; Grimbacher, B; Cunningham-Rundles, C; Stein, M; Helbert, M; Gathmann, B; Kindle, G; Knight, A K; Ochs, H D; Sullivan, K; Franco, J L

2009-01-01

35

Antibody-Mediated Neutralization of Primary Human Immunodeficiency Virus Type 1 Isolates: Investigation of the Mechanism of Inhibition  

PubMed Central

Human immunodeficiency virus type 1 (HIV-1) neutralization occurs when specific antibodies, mainly those directed against the envelope glycoproteins, inhibit infection, most frequently by preventing the entry of the virus into target cells. However, the precise mechanisms of neutralization remain unclear. Previous studies, mostly with cell lines, have produced conflicting results involving either the inhibition of virus attachment or interference with postbinding events. In this study, we investigated the mechanisms of neutralization by immune sera and compared the inhibition of peripheral blood mononuclear cells (PBMC) infection by HIV-1 primary isolates (PI) with the inhibition of T-cell line infection by T-cell line-adapted (TCLA) strains. We followed the kinetics of neutralization to determine at which step of the viral cycle the antibodies act. We found that neutralization of the TCLA strain HIV-1MN/MT-4 required an interaction between antibodies and cell-free virions before the addition of MT-4 cells, whereas PI were neutralized even after adsorption onto PBMC. In addition, the dose-dependent inhibition of HIV-1MN binding to MT-4 cells was strongly correlated with serum-induced neutralization. In contrast, neutralizing sera did not reduce the adhesion of PI to PBMC. Postbinding inhibition was also detected for HIV-1MN produced by and infecting PBMC, demonstrating that the mechanism of neutralization depends on the target cell used in the assay. Finally, we considered whether the different mechanisms of neutralization may reflect the recognition of qualitatively different epitopes on the surface of PI and HIV-1MN or whether they reflect differences in virus attachment to PBMC and MT-4 cells. PMID:11160727

Spenlehauer, Catherine; Kirn, Andre; Aubertin, Anne-Marie; Moog, Christiane

2001-01-01

36

High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1-infected long-term nonprogressors.  

PubMed Central

Lack of disease in long-term nonprogressors with human immunodeficiency virus type 1 (HIV-1) infection was strongly associated with very low copy numbers of HIV-1 DNA and RNA in peripheral blood mononuclear cells and plasma and the presence of high levels of anti-HIV-1 CD8+ memory cytotoxic T lymphocytes specific for Gag, Pol, and Env, compared with levels present in intermediate and advanced progressors. CD8+ memory cytotoxic T lymphocytes may have an important role in controlling HIV-1 replication and preventing disease in long-term nonprogressors. PMID:7637030

Rinaldo, C; Huang, X L; Fan, Z F; Ding, M; Beltz, L; Logar, A; Panicali, D; Mazzara, G; Liebmann, J; Cottrill, M

1995-01-01

37

Can we find a solution to the human immunodeficiency virus\\/acquired immune deficiency syndrome controversy?  

Microsoft Academic Search

The time of re-evaluation of the role of human immunodeficiency viruses in the pathogenesis of acquired immune deficiency syndrome has now come, now that methods are available for the direct detection of human immunodeficiency viruses and for the detection of cellular anti-human immunodeficiency virus immune reactions. It has been shown that human immunodeficiency virus infections are common among anti-human immunodeficiency

A. Hässig; L. Wen-Xi; K. Stampfli

1996-01-01

38

Glycosylation inhibitors and neuraminidase enhance human immunodeficiency virus type 1 binding and neutralization by mannose-binding lectin.  

PubMed

Mannose-binding lectin (MBL), a C-type lectin component of the human innate immune system, binds to the gp120 envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1). The objective of this study was to assess the effects of inhibitors of endoplasmic reticulum glucosidases and Golgi mannosidase as well as neuraminidase (NA) on the interaction between HIV and MBL. Production of HIV in the presence of the mannosidase I inhibitor deoxymannojirimycin (dMM) significantly enhanced binding of HIV to MBL and increased MBL neutralization of an M-tropic HIV primary isolate. In contrast, culturing HIV in the presence of alpha-glucosidase I and II inhibitors castanospermine and deoxynojirimycin only slightly affected virus binding and neutralization by MBL. Removal of sialic acid from HIV by NA also significantly enhanced virus binding and neutralization by MBL. Treatment of virus grown in the presence of dMM with endoglycosidase F1 substantially reduced binding to MBL, indicating that dMM increased MBL binding by increasing high-mannose carbohydrates on the virus. In contrast, endoglycosidase F1 did not decrease the MBL interaction with NA-treated virus, suggesting that NA exposed novel MBL binding sites. Treatment with dMM increased the immunocapture of HIV by monoclonal antibodies 2F5 and 2G12, indicating that altering the glycosylation of viral glycoproteins increases the accessibility or reactivity of some epitopes. This study shows that specific alterations of the N-linked carbohydrates on HIV gp120/gp41 can enhance MBL-mediated neutralization of virus by strengthening the interaction of HIV-1 with MBL. PMID:12560567

Hart, Melanie L; Saifuddin, Mohammed; Spear, Gregory T

2003-02-01

39

Mutations in the principal neutralization determinant of human immunodeficiency virus type 1 affect syncytium formation, virus infectivity, growth kinetics, and neutralization.  

PubMed Central

The principal neutralization determinant (PND) of human immunodeficiency virus type 1 envelope glycoprotein gp120 contains a conserved GPG sequence. The effects of a 29-amino-acid deletion of most of the PND, a 3-amino-acid deletion in the GPG sequence, and 16 single-amino-acid substitutions in the GPG sequence were determined in a transient expression assay. All mutant envelope glycoproteins were expressed at levels comparable to that of the wild-type envelope, and mutations in the GPG sequence did not affect processing to gp120 or, except for the 29-amino-acid deletion, binding to CD4. Of all of the mutants, only the GHG and GFG mutants induced formation of syncytia similar in size and number to those induced by the wild-type envelope. When the envelope expression level was increased 10-fold or more, several additional mutants (APG, GAG, GSG, GQG, GVG, and GPF) also induced syncytium formation. Transfection with infectious proviral molecular clones containing the GHG, GFG, APG, GAG, GSG, or GPF mutations induced production of viral particles; however, only the GPG, GHG, and GFG viruses produced active infections in CD4-bearing cells. Furthermore, whereas the wild-type virus was efficiently neutralized by PND polyclonal and monoclonal antibodies, the GHG- and GFG-containing viruses were not. These results show that mutations in the GPG sequence found within the PND do not affect envelope expression and do not significantly affect CD4 binding or production of viral particles but that they do affect the ability of the envelope to induce syncytia and those of the viral particles to infect CD4 cells and be neutralized by PND antibodies. Images PMID:1548744

Grimaila, R J; Fuller, B A; Rennert, P D; Nelson, M B; Hammarskjold, M L; Potts, B; Murray, M; Putney, S D; Gray, G

1992-01-01

40

Properties and mechanism of action of a 17 amino acid, V3 loop-specific microantibody that binds to and neutralizes human immunodeficiency virus type 1 virions  

Microsoft Academic Search

Only two virus-neutralizing peptide microantibodies (MicroAbs) have been described and little is known about their mode of action. This report concerns a 17 amino acid cyclized MicroAb, derived from the third complementarity-determining region of the heavy chain of MAb F58 (IgG1), that recognizes the same minimum epitope in the V3 loop of the gp120 envelope protein of human immunodeficiency virus

N. A. C. Jackson; M. Levi; B. Wahren; N. J. Dimmock

41

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

42

Profiling the Specificity of Neutralizing Antibodies in a Large Panel of Plasmas from Patients Chronically Infected with Human Immunodeficiency Virus Type 1 Subtypes B and C? †  

PubMed Central

Identifying the viral epitopes targeted by broad neutralizing antibodies (NAbs) that sometimes develop in human immunodeficiency virus type 1 (HIV-1)-infected subjects should assist in the design of vaccines to elicit similar responses. Here, we investigated the activities of a panel of 24 broadly neutralizing plasmas from subtype B- and C-infected donors using a series of complementary mapping methods, focusing mostly on JR-FL as a prototype subtype B primary isolate. Adsorption with gp120 immobilized on beads revealed that an often large but variable fraction of plasma neutralization was directed to gp120 and that in some cases, neutralization was largely mediated by CD4 binding site (CD4bs) Abs. The results of a native polyacrylamide gel electrophoresis assay using JR-FL trimers further suggested that half of the subtype B and a smaller fraction of subtype C plasmas contained a significant proportion of NAbs directed to the CD4bs. Anti-gp41 neutralizing activity was detected in several plasmas of both subtypes, but in all but one case, constituted only a minor fraction of the overall neutralization activity. Assessment of the activities of the subtype B plasmas against chimeric HIV-2 viruses bearing various fragments of the membrane proximal external region (MPER) of HIV-1 gp41 revealed mixed patterns, implying that MPER neutralization was not dominated by any single specificity akin to known MPER-specific monoclonal Abs. V3 and 2G12-like NAbs appeared to make little or no contribution to JR-FL neutralization titers. Overall, we observed significant titers of anti-CD4bs NAbs in several plasmas, but approximately two-thirds of the neutralizing activity remained undefined, suggesting the existence of NAbs with specificities unlike any characterized to date. PMID:18815292

Binley, James M.; Lybarger, Elizabeth A.; Crooks, Emma T.; Seaman, Michael S.; Gray, Elin; Davis, Katie L.; Decker, Julie M.; Wycuff, Diane; Harris, Linda; Hawkins, Natalie; Wood, Blake; Nathe, Cory; Richman, Douglas; Tomaras, Georgia D.; Bibollet-Ruche, Frederic; Robinson, James E.; Morris, Lynn; Shaw, George M.; Montefiori, David C.; Mascola, John R.

2008-01-01

43

The Membrane-Proximal External Region of the Human Immunodeficiency Virus Type 1 Envelope: Dominant Site of Antibody Neutralization and Target for Vaccine Design  

PubMed Central

Summary: Enormous efforts have been made to produce a protective vaccine against human immunodeficiency virus type 1; there has been little success. However, the identification of broadly neutralizing antibodies against epitopes on the highly conserved membrane-proximal external region (MPER) of the gp41 envelope protein has delineated this region as an attractive vaccine target. Furthermore, emerging structural information on the MPER has provided vaccine designers with new insights for building relevant immunogens. This review describes the current state of the field regarding (i) the structure and function of the gp41 MPER; (ii) the structure and binding mechanisms of the broadly neutralizing antibodies 2F5, 4E10, and Z13; and (iii) the development of an MPER-targeting vaccine. In addition, emerging approaches to vaccine design are presented. PMID:18322034

Montero, Marinieve; van Houten, Nienke E.; Wang, Xin; Scott, Jamie K.

2008-01-01

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

Increased neutralization sensitivity of recently emerged CXCR4-using human immunodeficiency virus type 1 strains compared to coexisting CCR5-using variants from the same patient.  

PubMed

CXCR4-using (X4) human immunodeficiency virus type 1 (HIV-1) variants evolve from CCR5-using (R5) variants relatively late in the natural course of infection in 50% of HIV-1 subtype B-infected individuals and subsequently coexist with R5 HIV-1 variants. This relatively late appearance of X4 HIV-1 variants is poorly understood. Here we tested the neutralization sensitivity for soluble CD4 (sCD4) and the broadly neutralizing antibodies IgG1b12, 2F5, 4E10, and 2G12 of multiple coexisting clonal R5 and (R5)X4 (combined term for monotropic X4 and dualtropic R5X4 viruses) HIV-1 variants that were obtained at two time points after the first appearance of X4 variants in five participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS. Recently emerged (R5)X4 viruses were significantly more sensitive to neutralization by the CD4-binding-site-directed agents sCD4 and IgG1b12 than their coexisting R5 viruses. This difference was less pronounced at the later time point. Early (R5)X4 variants from two out of four patients were also highly sensitive to neutralization by autologous serum (50% inhibition at serum dilutions of >200). Late (R5)X4 viruses from these two patients were neutralized at lower serum dilutions, which suggested escape of X4 variants from humoral immunity. Autologous neutralization of coexisting R5 and (R5)X4 variants was not observed in the other patients. In conclusion, the increased neutralization sensitivity of HIV-1 variants during the transition from CCR5 usage to CXCR4 usage may imply an inhibitory role for humoral immunity in HIV-1 phenotype evolution in some patients, thus potentially contributing to the late emergence of X4 variants. PMID:17079299

Bunnik, Evelien M; Quakkelaar, Esther D; van Nuenen, Ad C; Boeser-Nunnink, Brigitte; Schuitemaker, Hanneke

2007-01-01

46

Characterization of a discontinuous human immunodeficiency virus type 1 gp120 epitope recognized by a broadly reactive neutralizing human monoclonal antibody.  

PubMed Central

While one hypervariable, linear neutralizing determinant on the human immunodeficiency virus type 1 (HIV-1) gp120 envelope glycoprotein has been well characterized, little is known about the conserved, discontinuous gp120 epitopes recognized by neutralizing antibodies in infected individuals. Here, the epitope recognized by a broadly reactive neutralizing monoclonal antibody (F105) derived from an HIV-1-infected patient was characterized by examining the effects of changes in conserved gp120 amino acids on antibody reactivity. The F105 epitope was disrupted by changes in gp120 amino acids 256 and 257, 368 to 370, 421, and 470 to 484, which is consistent with the discontinuous nature of the epitope. Three of these regions are proximal to those previously shown to be important for CD4 binding, which is consistent with the ability of the F105 antibody to block gp120-CD4 interaction. Since F105 recognition was more sensitive to amino acid changes in each of the four identified gp120 regions than was envelope glycoprotein function, replication-competent mutant viruses that escaped neutralization by the F105 antibody were identified. These studies identify a conserved, functional HIV-1 gp120 epitope that is immunogenic in man and may serve as a target for therapeutic or prophylactic intervention. PMID:1717717

Thali, M; Olshevsky, U; Furman, C; Gabuzda, D; Posner, M; Sodroski, J

1991-01-01

47

Glycosylation inhibitors and neuraminidase enhance human immunodeficiency virus type 1 binding and neutralization by mannose-binding lectin  

Microsoft Academic Search

Mannose-binding lectin (MBL), a C-type lectin component of the human innate immune system, binds to the gp120 envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1). The objective of this studywas to assessthe effects of inhibitors of endoplasmic reticulum glucosidases and Golgi mannosidase as well as neuraminidase (NA) on the interaction between HIV and MBL. Production of HIV in the

Melanie L. Hart; Mohammed Saifuddin; Gregory T. Spear

2003-01-01

48

The Ability of an Oligomeric Human Immunodeficiency Virus Type 1 (HIV1) Envelope Antigen To Elicit Neutralizing Antibodies against Primary HIV1 Isolates Is Improved following Partial Deletion of the Second Hypervariable Region  

Microsoft Academic Search

Partial deletion of the second hypervariable region from the envelope of the primary-like SF162 virus increases the exposure of certain neutralization epitopes and renders the virus, SF162DV2, highly susceptible to neutralization by clade B and non-clade B human immunodeficiency virus (HIV-positive) sera (L. Stama- tatos and C. Cheng-Mayer, J. Virol. 78:7840-7845, 1998). This observation led us to propose that the

S. W. Barnett; S. Lu; I. Srivastava; S. Cherpelis; A. Gettie; J. Blanchard; S. Wang; I. Mboudjeka; L. Leung; Y. Lian; A. Fong; C. Buckner; A. Ly; S. Hilt; J. Ulmer; C. T. Wild; J. R. Mascola; L. Stamatatos

2001-01-01

49

Induction of Neutralizing Antibodies and Gag-Specific Cellular Immune Responses to an R5 Primary Isolate of Human Immunodeficiency Virus Type 1 in Rhesus Macaques  

PubMed Central

The ability to generate antibodies that cross-neutralize diverse primary isolates is an important goal for human immunodeficiency virus type 1 (HIV-1) vaccine development. Most of the candidate HIV-1 vaccines tested in humans and nonhuman primates have failed in this regard. Past efforts have focused almost entirely on the envelope glycoproteins of a small number of T-cell line-adapted strains of the virus as immunogens. Here we assessed the immunogenicity of noninfectious virus-like particles (VLP) consisting of Gag, Pro (protease), and Env from R5 primary isolate HIV-1Bx08. Immunogens were delivered to rhesus macaques in the form of either purified VLP, recombinant DNA and canarypox (ALVAC) vectors engineered to express VLP, or a combination of these products. Seroconversion to Gag and Pro was detected in all of the immunized animals. Antibodies that could neutralize HIV-1Bx08 were detected in animals that received (i) coinoculations with DNABx08 and VLPBx08, (ii) DNABx08 followed by ALVACBx08 boosting, and (iii) VLPBx08 alone. The neutralizing antibodies were highly strain specific despite the fact that they did not appear to be directed to linear epitopes in the V3 loop. Virus-specific cellular immune responses also were generated, as judged by the presence of Gag-specific gamma interferon (IFN-?)-producing cells. These cellular immune responses required the inclusion of DNABx08 in the immunization modality, since few or no IFN-?-producing cells were detected in animals that received either VLPBx08 or ALVACBx08 alone. The results demonstrate the feasibility of generating neutralizing antibodies and cellular immune responses that target an R5 primary HIV-1 isolate by vaccination in primates. PMID:11390589

Montefiori, David C.; Safrit, Jeffrey T.; Lydy, Shari L.; Barry, Ashley P.; Bilska, Miroslawa; Vo, Ha T. T.; Klein, Michel; Tartaglia, James; Robinson, Harriet L.; Rovinski, Benjamin

2001-01-01

50

Neutralization-Sensitive R5-Tropic Simian-Human Immunodeficiency Virus SHIV-2873Nip, Which Carries env Isolated from an Infant with a Recent HIV Clade C Infection?  

PubMed Central

Human immunodeficiency virus clade C (HIV-C) accounts for >56% of all HIV infections worldwide. To investigate vaccine safety and efficacy in nonhuman primates, a pathogenic, R5-tropic, neutralization-sensitive simian-human immunodeficiency virus (SHIV) carrying HIV-C env would be desirable. We have constructed SHIV-2873Ni, an R5-tropic SHIV carrying a primary pediatric HIV-C env gene isolated from a 2-month-old Zambian infant, who died within 1 year of birth. SHIV-2873Ni was constructed using SHIV-1157ipd3N4 (R. J. Song, A. L. Chenine, R. A. Rasmussen, C. R. Ruprecht, S. Mirshahidi, R. D. Grisson, W. Xu, J. B. Whitney, L. M. Goins, H. Ong, P. L. Li, E. Shai-Kobiler, T. Wang, C. M. McCann, H. Zhang, C. Wood, C. Kankasa, W. E. Secor, H. M. McClure, E. Strobert, J. G. Else, and R. M. Ruprecht. J. Virol. 80:8729-8738, 2006) as the backbone, since the latter contains additional NF-?B sites in the long terminal repeats to enhance viral replicative capacity. The parental virus, SHIV-2873Ni, was serially passaged through five rhesus monkeys (RMs); SHIV-2873Nip, the resulting passaged virus, was reisolated from the fourth recipient about 1 year postinoculation. SHIV-2873Nip was replication competent in RM peripheral blood mononuclear cells of all random donors tested and was exclusively R5 tropic, and its env gene clustered with HIV-C by phylogenetic analysis; its high sensitivity to neutralization led to classification as a tier 1 virus. Indian-origin RMs were inoculated by different mucosal routes, resulting in high peak viral RNA loads. Signs of virus-induced disease include depletion of gut CD4+ T lymphocytes, loss of memory T cells in blood, and thrombocytopenia that resulted in fatal cerebral hemorrhage. SHIV-2873Nip is a highly replication-competent, mucosally transmissible, pathogenic R5-tropic virus that will be useful to study viral pathogenesis and to assess the efficacy of immunogens targeting HIV-C Env. PMID:19019970

Siddappa, Nagadenahalli B.; Song, Ruijiang; Kramer, Victor G.; Chenine, Agnes-Laurence; Velu, Vijayakumar; Ong, Helena; Rasmussen, Robert A.; Grisson, Ricky D.; Wood, Charles; Zhang, Hong; Kankasa, Chipeppo; Amara, Rama Rao; Else, James G.; Novembre, Francis J.; Montefiori, David C.; Ruprecht, Ruth M.

2009-01-01

51

Distinction of human immunodeficiency virus type 1 neutralization and infection enhancement by human monoclonal antibodies to glycoprotein 120.  

PubMed Central

There is increasing evidence that sera from HIV-1-infected individuals contain antibodies that enhance infection by HIV-1 in vitro. Previous work has demonstrated that complement receptors on T lymphoid cells and Fc receptors for IgG (Fc gamma R) on monocytic cells are required for enhanced infection by antibody-complexed HIV-1. Characterization of such infection-enhancing antibodies is essential because immunogenic epitopes which induce enhancing antibodies should be excluded from HIV-1 vaccines. This study was conducted to identify enhancing antibodies involved in Fc R-mediated enhancement of HIV-1 infection employing IgG human monoclonal antibodies (HMAbs) reactive against gp120 of HIV-1, which were produced by B cell lines derived from an HIV-1-infected individual. A potent neutralizing HMAb N70-1.5e did not enhance infection by HIV-1 (IIIB and MN strains), whereas HMAb N70-2.3a mediated enhancement of HIV-1 infection, but had little neutralizing activity. A competition radio immunoassay demonstrated that the two antibodies bind to distinct epitopes. These results indicated that enhancing and neutralizing antibodies can be induced by different epitopes on gp120, suggesting the potential for development of safe vaccines against HIV-1 by exclusion of immunogenic epitopes for enhancing antibodies. We made attempts to identify the epitope on gp120 that is recognized by the enhancing antibody N70-2.3a by using recombinant HIV-1 proteins and found that the antibody binds to a conformational site of nonvariable sequences in the carboxyl half (aa 272-509) of gp120. PMID:1376330

Takeda, A; Robinson, J E; Ho, D D; Debouck, C; Haigwood, N L; Ennis, F A

1992-01-01

52

Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody response  

PubMed Central

Background Differently from HIV-1, HIV-2 disease progression usually takes decades without antiretroviral therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4+ T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected at birth. Results CD4+ T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4+ T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5 isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a ?-hairpin structure were related with rate of escape from the neutralizing antibodies. Conclusion Our data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which Nabs play an important role in HIV-2 pathogenesis. PMID:24156513

2013-01-01

53

Modeling how many envelope-glycoprotein trimers per virion participate in human immunodeficiency virus infectivity and its neutralization by antibody  

PubMed Central

Trimers of the HIV-1 envelope glycoprotein (Env) effectuate viral entry into susceptible cells. Therefore Env trimers are the targets for neutralizing antibodies. This study models the number of trimers required for virion infectivity. It also delineates the minimum number of antibody molecules that would neutralize a virion. First, Env function was assumed to be incremental (all envelope-glycoprotein units contribute equally) or liminal (characterized by thresholds). Then, such models were combined and shown to fit published data on phenotypically mixed pseudotype viruses. Virions with 9 trimers would require around a median of 5 of them for strong infectivity; the proportion varies among strains and mutants. In addition, the models account for both liminal and incremental protomeric effects at the trimer level: Different inert Env mutants may affect trimer function in different degrees. Because of compensatory effects at the virion and trimer levels, however, current data cannot differentiate between all plausible models. But the biophysically and mathematically rationalized blurring of thresholds yields candidate models that fit different data excellently. PMID:17825343

Klasse, Per Johan

2007-01-01

54

Fine Definition of the Epitope on the gp41 Glycoprotein of Human Immunodeficiency Virus Type 1 for the Neutralizing Monoclonal Antibody 2F5  

PubMed Central

Matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS), in combination with proteolytic protection assays, has been used to identify the functional epitope on human immunodeficiency virus envelope glycoprotein gp41 for the broadly neutralizing anti-gp41 human monoclonal antibody 2F5. In this protection assay-based procedure, a soluble gp140 protein with a stabilizing intermolecular disulfide bond between the gp120 and gp41 subunits (SOS gp140) was affinity bound to immobilized 2F5 under physiological conditions. A combination of proteolytic enzymatic cleavages was then performed to remove unprotected residues. Residues of SOS gp140 protected by their binding to 2F5 were then identified based on their molecular weights as determined by direct MALDI-MS of the immobilized antibody beads. The epitope, NEQELLELDKWASLWN, determined by this MALDI-MS protection assay approach consists of 16 amino acid residues near the C terminus of gp41. It is significantly longer than the ELDKWA core epitope previously determined for 2F5 by peptide enzyme-linked immunosorbent assay. This new knowledge of the structure of the 2F5 epitope may facilitate the design of vaccine antigens intended to induce antibodies with the breadth and potency of action of the 2F5 monoclonal antibody. PMID:11602730

Parker, Carol E.; Deterding, Leesa J.; Hager-Braun, Christine; Binley, James M.; Schulke, Norbert; Katinger, Hermann; Moore, John P.; Tomer, Kenneth B.

2001-01-01

55

Differential CD4/CCR5 Utilization, gp120 Conformation, and Neutralization Sensitivity between Envelopes from a Microglia-Adapted Human Immunodeficiency Virus Type 1 and Its Parental Isolate  

PubMed Central

Human immunodeficiency virus type 1 (HIV-1) infects and induces syncytium formation in microglial cells from the central nervous system (CNS). A primary isolate (HIV-1BORI) was sequentially passaged in cultured microglia, and the isolate recovered (HIV-1BORI-15) showed high levels of fusion and replicated more efficiently in microglia (J. M. Strizki, A. V. Albright, H. Sheng, M. O'Connor, L. Perrin, and F. González-Scarano, J. Virol. 70:7654–7662, 1996). The parent and adapted viruses used CCR5 as coreceptor. Recombinant viruses demonstrated that the syncytium-inducing phenotype was associated with four amino acid differences in the V1/V2 region of the viral gp120 (J. T. C. Shieh, J. Martin, G. Baltuch, M. H. Malim, and F. González-Scarano, J. Virol. 74:693–701, 2000). We produced luciferase-reporter, env-pseudotyped viruses using plasmids containing env sequences from HIV-1BORI, HIV-1BORI-15, and the V1/V2 region of HIV-1BORI-15 in the context of HIV-1BORI env (named rBORI, rB15, and rV1V2, respectively). The pseudotypes were used to infect cells expressing various amounts of CD4 and CCR5 on the surface. In contrast to the parent recombinant, the rB15 and rV1V2 pseudotypes retained their infectability in cells expressing low levels of CD4 independent of the levels of CCR5, and they infected cells expressing CD4 with a chimeric coreceptor containing the third extracellular loop of CCR2b in the context of CCR5 or a CCR5 ?4 amino-terminal deletion mutant. The VH-rB15 and VH-rV1V2 recombinant viruses were more sensitive to neutralization by a panel of HIV-positive sera than was VH-rBORI. Interestingly, the CD4-induced 17b epitope on gp120 was more accessible in the rB15 and rV1V2 pseudotypes than in rBORI, even before CD4 binding, and concomitantly, the rB15 and rV1V2 pseudotypes were more sensitive to neutralization with the human 17b monoclonal antibody. Adaptation to growth in microglia—cells that have reduced expression of CD4 in comparison with other cell types—appears to be associated with changes in gp120 that modify its ability to utilize CD4 and CCR5. Changes in the availability of the 17b epitope indicate that these affect conformation. These results imply that the process of adaptation to certain tissue types such as the CNS directly affects the interaction of HIV-1 envelope glycoproteins with cell surface components and with humoral immune responses. PMID:11264346

Martin, Julio; LaBranche, Celia C.; Gonzalez-Scarano, Francisco

2001-01-01

56

Infection of Specific Dendritic Cells by CCR5Tropic Human Immunodeficiency Virus Type 1 Promotes Cell-Mediated Transmission of Virus Resistant to Broadly Neutralizing Antibodies  

Microsoft Academic Search

The tropism of human immunodeficiency virus type 1 for chemokine receptors plays an important role in the transmission of AIDS. Although CXCR4-tropic virus is more cytopathic for T cells, CCR5-tropic strains are transmitted more frequently in humans for reasons that are not understood. Phenotypically immature myeloid dendritic cells (mDCs) are preferentially infected by CCR5-tropic virus, in contrast to mature mDCs,

Lakshmanan Ganesh; Kwanyee Leung; Karin Lore; Reuven Levin; Amos Panet; Owen Schwartz; Richard A. Koup; Gary J. Nabel

2004-01-01

57

Primary Immunodeficiency  

MedlinePLUS

... kidneys, and other organs, causing rashes, joint pain, fatigue, and fever, among other things. Finally, an immunodeficiency ... The Jeffrey Modell Foundation and the American Red Cross. Eight or more new ear infections within a ...

58

[Primary immunodeficiency].  

PubMed

Primary (inborn) immunodeficiency is caused by gene defects that impact both the innate and the adaptive immune system. Individuals with an immunedeficiency primarily come to medical attention with recurrent infections. Most diagnoses are first made in childhood and include cellular immunodeficiency, defects of phagocyte function and other primary immunodeficiencies. Antibody deficiencies, particularly common variable immunodeficiency (CVID) and complement defects may, however, not become manifested until adulthood. A pathological susceptibility to infection in adults is defined as more than three infections per year that require treatment with antibiotics and last longer than 4 weeks each. Clinical clues for immunodeficiency are pathological susceptibility to infections and immune dysregulation. The former is characterized by frequent and severe infections with often unusual pathogens, localization, course and/or intensity. Immune dysregulation comprises granulomas, autoimmune diseases, recurrent fever/chronic inflammation, tendency to eczema, lymphoproliferation and chronic enteritis. There are evidence-based guidelines and consensus documents for the diagnosis and treatment of primary immunodeficiencies. Therapeutic approaches depend on the nature of the immune defect and range from immunoglobulin substitution for antibody deficiencies to bone marrow transplantation for severe cellular immune defects. PMID:23989691

Engelhardt, K R; Grimbacher, B; Niehues, T

2013-09-01

59

Induction of Systemic and Mucosal Cross-Clade Neutralizing Antibodies in BALB/c Mice Immunized with Human Immunodeficiency Virus Type 1 Clade A Virus-Like Particles Administered by Different Routes of Inoculation  

PubMed Central

We have recently developed a candidate human immunodeficiency virus type 1 (HIV-1) vaccine model, based on virus-like particles (VLPs) expressing gp120 from a Ugandan HIV-1 isolate of clade A (HIV-VLPAs), which shows the induction of neutralizing antibodies as well as cytotoxic T lymphocytes (CTL) in BALB/c mice by intraperitoneal (i.p.) administration. In the present study, immunization experiments based on a multiple-dose regimen have been performed with BALB/c mice to compare different routes of administration. i.p. and intranasal (i.n.), but not oral, administration induce systemic as well as mucosal (vaginal and intestinal) immunoglobulin G (IgG) and IgA responses. These immune sera exhibit >50% ex vivo neutralizing activity against both autologous and heterologous primary isolates. Furthermore, the administration of HIV-VLPAs by the i.n. immunization route induces a specific CTL activity, although at lower efficiency than the i.p. route. The HIV-VLPAs represent an efficient strategy to stimulate both arms of immunity; furthermore, the induction of specific humoral immunity at mucosal sites, which nowadays represent the main port of entry for HIV-1 infection, is of great interest. All these properties, and the possible cross-clade in vivo protection, could make these HIV-VLPAs a good candidate for a mono- and multicomponent worldwide preventive vaccine approach not restricted to high-priority regions, such as sub-Saharan countries. PMID:15890945

Buonaguro, L.; Visciano, M. L.; Tornesello, M. L.; Tagliamonte, M.; Biryahwaho, B.; Buonaguro, F. M.

2005-01-01

60

Cryptic Nature of a Conserved, CD4-Inducible V3 Loop Neutralization Epitope in the Native Envelope Glycoprotein Oligomer of CCR5-Restricted, but Not CXCR4-Using, Primary Human Immunodeficiency Virus Type 1 Strains  

PubMed Central

The external subunit of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env), gp120, contains conserved regions that mediate sequential interactions with two cellular receptor molecules, CD4 and a chemokine receptor, most commonly CCR5 or CXCR4. However, antibody accessibility to such regions is hindered by diverse protective mechanisms, including shielding by variable loops, conformational flexibility and extensive glycosylation. For the conserved neutralization epitopes hitherto described, antibody accessibility is reportedly unrelated to the viral coreceptor usage phenotype. Here, we characterize a novel, conserved gp120 neutralization epitope, recognized by a murine monoclonal antibody (MAb), D19, which is differentially accessible in the native HIV-1 Env according to its coreceptor specificity. The D19 epitope is contained within the third variable (V3) domain of gp120 and is distinct from those recognized by other V3-specific MAbs. To study the reactivity of MAb D19 with the native oligomeric Env, we generated a panel of PM1 cells persistently infected with diverse primary HIV-1 strains. The D19 epitope was conserved in the majority (23/29; 79.3%) of the subtype-B strains tested, as well as in selected strains from other genetic subtypes. Strikingly, in CCR5-restricted (R5) isolates, the D19 epitope was invariably cryptic, although it could be exposed by addition of soluble CD4 (sCD4); epitope masking was dependent on the native oligomeric structure of Env, since it was not observed with the corresponding monomeric gp120 molecules. By contrast, in CXCR4-using strains (X4 and R5X4), the epitope was constitutively accessible. In accordance with these results, R5 isolates were resistant to neutralization by MAb D19, becoming sensitive only upon addition of sCD4, whereas CXCR4-using isolates were neutralized regardless of the presence of sCD4. Other V3 epitopes examined did not display a similar divergence in accessibility based on coreceptor usage phenotype. These results provide the first evidence of a correlation between HIV-1 biological phenotype and neutralization sensitivity, raising the possibility that the in vivo evolution of HIV-1 coreceptor usage may be influenced by the selective pressure of specific host antibodies. PMID:15890935

Lusso, Paolo; Earl, Patricia L.; Sironi, Francesca; Santoro, Fabio; Ripamonti, Chiara; Scarlatti, Gabriella; Longhi, Renato; Berger, Edward A.; Burastero, Samuele E.

2005-01-01

61

Host range mutant of human immunodeficiency virus type 1: modification of cell tropism by a single point mutation at the neutralization epitope in the env gene.  

PubMed Central

We have isolated a variant of human immunodeficiency virus type 1 (HIV-1) which is highly infectious to fibroblastlike cells (BT cells) derived from human brain as well as CD4-positive T cells. This variant HIV-1, named HIV[GUN-1V], was obtained by infecting BT cells with a prototype HIV-1 isolate, named HIV[GUN-1WT], which is highly infectious to T cells but barely infectious to BT cells. HIV[GUN-1V] infects BT cells productively and this infection appeared to be mediated by CD4. To elucidate the viral gene responsible for the host range difference between the variant and prototype HIV-1s, we cloned and analyzed the provirus genomes of the two viruses. Examination of the infectivities of BT cells by various recombinant viruses and analyses of the nucleotide sequences of HIV[GUN-1V] and HIV[GUN-1WT] showed that a single nucleotide exchange was responsible for their difference in infectivity of BT cells: HIV[GUN-1V] contains a thymine residue instead of the cytosine residue in HIV[GUN-1WT] at position 931 of the env coding sequence. Replacement of cytosine by thymine at this position of the env coding sequence of the HIV[GUN-1WT] genome induced the ability to infect BT cells. The base exchange at this position was expected to change amino acid 311 of the envelope glycoprotein, gp120, from proline to serine, which is located in a variable region containing type-specific immunodominant epitopes. Thus, HIV[GUN-1V] acquired a wider host range than HIV[GUN-1WT] by a single point mutation in the env gene. Images PMID:2002539

Takeuchi, Y; Akutsu, M; Murayama, K; Shimizu, N; Hoshino, H

1991-01-01

62

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

63

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

64

Natural killer cell inhibits human immunodeficiency virus replication in chronically infected immune cells  

Microsoft Academic Search

Natural killer (NK) cells are a crucial component of the host innate immune system. We investigated the noncytolytic anti-human immunodeficiency virus (HIV) activity of NK cells in chronically HIV-infected immune cells. Supernatants collected from NK cell cultures (both primary NK cells and NK cell lines, YTS and NK 92) inhibited HIV activation in peripheral blood mononuclear cells (PBMCs) from HIV-infected

Ting Zhang; Yuan Li; Yan-Jian Wang; Xu Wang; Mike Young; Steven D. Douglas; Wen-Zhe Ho

2007-01-01

65

Testing for Human Immunodeficiency Virus  

MedlinePLUS

Testing for Human Immunodeficiency Virus The American College of Obstetricians and Gynecologists Women’s Health Care Physicians patient education Fact Sheet PFS005: Testing for Human Immunodeficiency ...

66

Stimulation of neutralizing antibodies to human immunodeficiency virus type 1 in three strains of mice immunized with a 22 amino acid peptide of gp41 expressed on the surface of a plant virus  

Microsoft Academic Search

A plant virus, cowpea mosaic virus, expressing a 22 amino acid peptide 731–752 of the gp41 glycoprotein of human immunodeficency virus type 1 (HIV-1 IIIB), was shown previously to stimulate HIV-1 cross reactive neutralizing antibodies in adult C57BL6 mice. Here some parameters concerning the stimulation of HIV-1-specific neutralizing and ELISA antibody have been determined in adult C57BL6, C3HHe-mg and BALBc

Lesley McLain; Zarmina Durrani; Lisa Ann Wisniewski; Claudine Porta; George P. Lomonossoff; Nigel J. Dimmock

1996-01-01

67

l-Chicoric acid, an inhibitor of human immunodeficiency virus type 1 (HIV1) integrase, improves on the in vitro anti-HIV1 effect of Zidovudine plus a protease inhibitor (AG1350)  

Microsoft Academic Search

Combinations of anti-human immunodeficiency virus (HIV) drugs, including reverse transcriptase inhibitors and protease inhibitors, have proven immensely potent in the therapy of acquired immune deficiency syndrome (AIDS). To determine whether HIV integrase is a suitable target for combination therapy, the ability of an HIV integrase inhibitor, l-chicoric acid, to work in combination with a protease inhibitor and Zidovudine was tested

W Edward Robinson

1998-01-01

68

Common Variable Immunodeficiency (CVID)  

MedlinePLUS

... on. Read more information on enabling JavaScript. Primary Immune Deficiency Diseases Skip Content Marketing Share this: Main Content Area Common Variable Immunodeficiency (CVID) Crystal structure of the antibody immunoglobulin ...

69

Anti-human coronavirus (anti-HCoV) triterpenoids from the leaves of Euphorbia neriifolia.  

PubMed

Euphorbia neriifolia L. is a spiny herb native to Southeast Asia and currently cultivated in southern Taiwan. From the ethanolic extract of E. neriifolia leaves, 23 compounds were isolated, including 22 triterpenoids and one flavonoid glycoside. The anti-human coronavirus (HCoV) activity of the separated triterpenoids was studied revealing the structure-activity relationship (SAR) of these isolates. 3beta-Friedelanol exhibited more potent anti-viral activity than the positive control, actinomycin D, which implies the importance of the friedelane skeleton as a potential scaffold for developing new anti-HCoV-229E drugs. PMID:23285797

Chang, Fang-Rong; Yen, Chiao-Ting; Ei-Shazly, Mohamed; Lin, Wen-Hsun; Yen, Ming-Hong; Lin, Kuei-Hsiang; Wu, Yang-Chang

2012-11-01

70

[Cancer and primary humoral immunodeficiency].  

PubMed

The occurrence of cancers in patients with primary humoral immunodeficiency syndrome (X-linked agammaglobulinemia, common variable immunodeficiency, IgA deficiency) is more than mere coincidence. An increased risk of non Hodgkin's lymphoma and gastric adenocarcinoma, particularly for patients with common variable immunodeficiency, is well established. A literature review is presented on this subject with analysis of case reports, prospective and retrospective studies, and data from the Minnesota Immunodeficiency Cancer Registry. PMID:9339187

Zenone, T; Souillet, G

1997-08-01

71

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

72

Common variable immunodeficiency  

Microsoft Academic Search

Common variable immunodeficiency (CVID) is a common primary immnodeficiency disease, the hallmark of which is hypogammaglobulinemia.\\u000a Due to the lack of antibodies, patients usually have recurrent bacterial infections, but there are a number of other puzzling\\u000a manifestations, including inflammatory conditions, autoimmune disease, and the development of lymphomas. Most patients are\\u000a diagnosed as adults, and delay in the recognition of the

Charlotte Cunningham-Rundles

2001-01-01

73

Inhibition of gallium-67 uptake in melanoma by an anti-human transferrin receptor monoclonal antibody  

SciTech Connect

The effect of an anti-human transferrin receptor (anti-TFR) monoclonal antibody (MoAb), designated B3/25, and an anti-melanoma antibody, designated 96.5, on the uptake of gallium-67 (/sup 67/Ga) by tumor was studied. Three groups of six athymic mice bearing a human melanoma were injected via tail vein with (a) 0.55 mg human serum albumin (HSA) (control group), (b) 0.5 mg MoAb B3/25 + 0.55 mg HSA, and (c) 0.5 mg MoAb 96.5 + 0.55 mg HSA, respectively. Twenty-four hours later, each mouse was given an intravenous dose of 5 microCi (/sup 67/Ga) citrate. Biodistribution of activity (percent injected dose per gram) determined 48 hr after injection of /sup 67/Ga showed a 75% decrease in tumor uptake in the group of mice that received B3/25 (anti-TFR MoAb) compared with the control group. In contrast, MoAb 96.5 did not show any effect on melanoma uptake of /sup 67/Ga. Histologic findings suggest that the decreased uptake was not due to cellular damage resulting from binding of B3/25 to TFR. The results of this study strongly suggest the involvement of TFR in the in vivo tumor uptake of /sup 67/Ga.

Chan, S.M.; Hoffer, P.B.; Maric, N.; Duray, P.

1987-08-01

74

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation  

PubMed Central

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.

2013-01-01

75

Demonstration and characterization of anti-human mitochondria autoantibodies in idiopathic hypoparathyroidism and in other conditions.  

PubMed Central

We studied 32 patients with idiopathic hypoparathyroidism (IHP), 19 patients with organ-specific autoimmune diseases (OSAD) without IHP, 50 normal controls and a known serum with anti-mitochondrial autoantibodies (AMA). Patients' sera were tested by the classical indirect immunofluorescent technique and by the indirect immunofluorescent complement fixation technique on unfixed cryostat sections of normal human parathyroid, pancreas, thyroid, stomach, kidney, and rat kidney. Five out of 32 patients with IHP, three out of 19 patients with OSAD without IHP and one out of 50 normal controls revealed a bright reactivity against oxyphil cells and a weak reactivity against chief cells of normal parathyroid. These sera also brightly reacted with mitochondria-rich cells and weakly with the remaining cells of only human tissues. The absorption of positive sera with human mitochondria completely abolished this positivity but the absorption with rat mitochondria failed to prevent this reaction. This reactivity was due to an anti-human mitochondrial autoantibody (AHMA) of IgG class. By non-competitive ELISA and Western blot we also demonstrated that every AHMA-positive serum mainly reacted against a human mitochondrial membrane-bound protein of approximate mol. wt. of 46 kd, while the AMA-positive serum reacted against different mitochondrial antigens. The present study shows that a specific parathyroid autoantibody was not detectable in patients with IHP. Images Fig. 3 PMID:3910313

Betterle, C; Caretto, A; Zeviani, M; Pedini, B; Salviati, C

1985-01-01

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

Anti-AIDS agents. 78. Design, synthesis, metabolic stability assessment, and antiviral evaluation of novel betulinic acid derivatives as potent anti-human immunodeficiency virus (HIV) agents.  

PubMed

In a continuing study of potent anti-HIV agents, seventeen 28,30-disubstituted betulinic acid (BA, 1) derivatives and seven novel 3,28-disubstituted BA analogues were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, compound 21 showed an improved solubility and equal anti-HIV potency (EC(50) = 0.09 microM) when compared to HIV entry inhibitors 3b (IC9564, (3R,4S)-N'-[N-[3beta-hydroxy-lup-20(29)-en-28-oyl]-8-aminooctanoyl]-4-amino-3-hydroxy-6-methylheptanoic acid) and 4 (A43-D, [[N-[3beta-O-(3',3'-dimethylsuccinyl)-lup-20(29)-en-28-oyl]-7-aminoheptyl]carbamoyl]methane). Using a cyclic secondary amine to form the C-28 amide bond increased the metabolic stability of the derivatives significantly in pooled human liver microsomes. The most potent compounds 47 and 48 displayed potent anti-HIV activity with EC(50) values of 0.007 and 0.006 microM, respectively. These results are slightly better than that of bevirimat (2, 3',3'-dimethylsuccinylbetulinic acid), which is currently in phase IIb clinical trials. Compounds 47 and 48 should serve as attractive promising leads to develop next generation, metabolically stable, 3,28-disubstituted bifunctional HIV-1 inhibitors as clinical trials candidates. PMID:19388685

Qian, Keduo; Yu, Donglei; Chen, Chin-Ho; Huang, Li; Morris-Natschke, Susan L; Nitz, Theodore J; Salzwedel, Karl; Reddick, Mary; Allaway, Graham P; Lee, Kuo-Hsiung

2009-05-28

78

Anti-AIDS Agents 78 †. Design, Synthesis, Metabolic Stability Assessment, and Antiviral Evaluation of Novel Betulinic Acid Derivatives as Potent Anti-Human Immunodeficiency Virus (HIV) Agents  

PubMed Central

In a continuing study of potent anti-HIV agents, seventeen 28,30-disubstituted betulinic acid (BA, 1) derivatives, as well as seven novel 3,28-disubstituted BA analogs were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, compound 21 showed an improved solubility and equal anti-HIV potency (EC50: 0.09 ?M), when compared to HIV entry inhibitors 3b (IC9564) and 4 (A43-D). Using a cyclic secondary amine to form the C-28 amide bond increased the metabolic stability of the derivatives significantly in pooled human liver microsomes. The most potent compounds 47 and 48 displayed potent anti-HIV activity with EC50 values of 0.007 ?M and 0.006 ?M, respectively. These results are slightly better than that of bevirimat (2), which is currently in Phase IIb clinical trials. Compounds 47 and 48 should serve as attractive promising leads to develop next generation, metabolically stable, 3,28-disubstituted bifunctional HIV-1 inhibitors as clinical trials candidates. PMID:19388685

Qian, Keduo; Yu, Donglei; Chen, Chin-Ho; Huang, Li; Morris-Natschke, Susan L.; Nitz, Theodore J.; Salzwedel, Karl; Reddick, Mary; Allaway, Graham P.; Lee, Kuo-Hsiung

2009-01-01

79

Influence of the antileukemic and anti-human immunodeficiency virus agent avarol on selected immune responses in vitro and in vivo.  

PubMed

The effect of the antileukemic and anti-HIV agent avarol on the lymphoid system was studied both in vitro and in vivo. Radioactively labelled avarol ([3H]-dihydroavarol) was found to accumulate in vitro in the cytoplasmic compartment primarily of T-lymphocytes and not of B-lymphocytes. Avarol increased significantly the IgG and IgM production by cultures of human lymphoid cells (unseparated) in vitro and slightly the number of plaque forming cells in vivo in spleen of mice. Moreover, a pretreatment of mice with avarol resulted in a higher [3H]-dThd incorporation rate in both macrophage-containing and macrophage-depleted lymphocyte cultures in vitro. The stimulatory influence of avarol on humoral immune responses is not accompanied by a change of the antibody-mediated hypersensitivity reaction, as measured by the Arthus reaction. No significant influence of avarol on the cellular immune system in vivo (rats or mice) was found, as taken from studies on delayed-type hypersensitivity reactions to sheep red blood cells and to oxazolone. The in vitro and animal data indicate that avarol combines useful properties (anti-HIV efficiency in vitro and augmentation of humoral immune responses) to consider it as a potential anti-AIDS agent. PMID:3555507

Müller, W E; Sobel, C; Diehl-Seifert, B; Maidhof, A; Schröder, H C

1987-05-01

80

[Common variable immunodeficiency].  

PubMed

Common variable immunodeficiency (CVI) is a heterogeneous syndrome characterized by defective antibody formation, resulting in abnormally low serum immunoglobulin levels. Clinical presentation usually includes recurrent infections of the respiratory tract, mostly induced by capsular bacteria. Patients are also highly prone to Giardia lamblia infections and related gastrointestinal disorders, as well as to a variety of autoimmune diseases which appear in approximately 20% of them. In addition, CVI can be frequently associated with a non-Hodgkin lymphoma or gastric carcinoma. In spite of its relatively frequent occurrence, the pathogenesis of CVI still remains poorly defined. In this review the authors describe clinical features, immunological abnormalities and replacement treatment with intravenous immunoglobulins of this antibody deficiency syndrome. PMID:9102704

Silvestris, N; Silvestris, F; Russo, S; Dammacco, F

1996-12-01

81

Antiviral Drugs for Viruses Other Than Human Immunodeficiency Virus  

PubMed Central

Most viral diseases, with the exception of those caused by human immunodeficiency virus, are self-limited illnesses that do not require specific antiviral therapy. The currently available antiviral drugs target 3 main groups of viruses: herpes, hepatitis, and influenza viruses. With the exception of the antisense molecule fomivirsen, all antiherpes drugs inhibit viral replication by serving as competitive substrates for viral DNA polymerase. Drugs for the treatment of influenza inhibit the ion channel M2 protein or the enzyme neuraminidase. Combination therapy with Interferon-? and ribavirin remains the backbone treatment for chronic hepatitis C; the addition of serine protease inhibitors improves the treatment outcome of patients infected with hepatitis C virus genotype 1. Chronic hepatitis B can be treated with interferon or a combination of nucleos(t)ide analogues. Notably, almost all the nucleos(t) ide analogues for the treatment of chronic hepatitis B possess anti–human immunodeficiency virus properties, and they inhibit replication of hepatitis B virus by serving as competitive substrates for its DNA polymerase. Some antiviral drugs possess multiple potential clinical applications, such as ribavirin for the treatment of chronic hepatitis C and respiratory syncytial virus and cidofovir for the treatment of cytomegalovirus and other DNA viruses. Drug resistance is an emerging threat to the clinical utility of antiviral drugs. The major mechanisms for drug resistance are mutations in the viral DNA polymerase gene or in genes that encode for the viral kinases required for the activation of certain drugs such as acyclovir and ganciclovir. Widespread antiviral resistance has limited the clinical utility of M2 inhibitors for the prevention and treatment of influenza infections. This article provides an overview of clinically available antiviral drugs for the primary care physician, with a special focus on pharmacology, clinical uses, and adverse effects. PMID:21964179

Razonable, Raymund R.

2011-01-01

82

Autoimmunity in Common Variable Immunodeficiency  

Microsoft Academic Search

Background  Autoimmunity has been increasingly recognized as a major issue in patients with common variable immunodeficiency (CVID), the\\u000a most common symptomatic primary immunodeficiency in adulthood. Different authors report high prevalences of autoimmune diseases\\u000a in CVID, and several mechanisms have been proposed to explain this apparent paradox. Genetic predisposition, under current\\u000a surveillance, innate and adaptive immunity deficiencies leading to persistent\\/recurrent infections, variable

Susana Lopes-da-Silva; Luiz Vicente Rizzo

2008-01-01

83

Nature of Nonfunctional Envelope Proteins on the Surface of Human Immunodeficiency Virus Type 1  

Microsoft Academic Search

Human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies are thought be distinguished from nonneutralizing antibodies by their ability to recognize functional gp120\\/gp41 envelope glycoprotein (Env) trimers. The antibody responses induced by natural HIV-1 infection or by vaccine candidates tested to date consist largely of nonneutralizing antibodies. One might have expected a more vigorous neutralizing response, particularly against virus particles that

Penny L. Moore; Emma T. Crooks; Lauren Porter; Ping Zhu; Charmagne S. Cayanan; Henry Grise; Paul Corcoran; Michael B. Zwick; Michael Franti; Lynn Morris; Kenneth H. Roux; Dennis R. Burton; James M. Binley

2006-01-01

84

A novel anti-human ICOSL monoclonal antibody that enhances IgG production of B cells.  

PubMed

ICOSL, a newly identified member of the B7 superfamily, plays a major role in immune responses. In this study, a functional anti-human ICOSL monoclonal antibody (MAb) 3B3 was obtained and characterized by means of flow cytometry, Western blot, and competition assay. This MAb could specifically recognize a distinct epitope of the ICOSL molecule. As a functional antibody, MAb 3B3 could inhibit the proliferation of T lymphocytes stimulated by ICOSL-L929 transfectants. Furthermore, it could enhance IgG production of PWM-driven B cells. The results indicate that the ICOS-ICOSL signal is critically involved in specific humoral immunity. PMID:23607348

Chen, Jie; Wang, Fengming; Cai, Qiuping; Shen, Shuang; Chen, Youguo; Hao, Chao; Sun, Jing

2013-04-01

85

Autosomal-dominant primary immunodeficiencies.  

PubMed

The vast majority of known primary immunodeficiencies (PIDs) are autosomal or X-linked recessive Mendelian traits. Only four classical primary immunodeficiencies are thought to be autosomal-dominant, three of which still lack a well-defined genetic etiology: isolated congenital asplenia, isolated chronic mucocutaneous candidiasis, and hyper IgE syndrome. The large deletions on chromosome 22q11.2 associated with Di George syndrome suggest that this disease may be dominant but not Mendelian, possibly involving several genes. The clinical and genetic features of six novel autosomal-dominant primary immunodeficiencies have however been described in recent years. These primary immunodeficiencies are caused by germline mutations in seven genes: ELA2, encoding a neutrophil elastase, and GFI1, encoding a regulator of ELA2 (mutations associated with severe congenital neutropenia); CXCR4, encoding a chemokine receptor (warts, hypogammaglobulinemia, infections and myelokathexis syndrome); LCRR8, encoding a key protein for B-cell development (agammaglobulinemia); IFNGR1, encoding the ligand-binding chain of the interferon-gamma receptor; STAT1, encoding the signal transducer and activator of transcription 1 downstream from interferon-gammaR1 (Mendelian susceptibility to mycobacterial diseases); and IKBA, encoding IkappaBalpha, the inhibitor alpha of NF-kappaB (anhidrotic ectodermal dysplasia with immunodeficiency). These recent data suggest that many more autosomal-dominant PIDs are likely to be identified in the near future. PMID:15604887

Lawrence, Tatiana; Puel, Anne; Reichenbach, Janine; Ku, Cheng-Lung; Chapgier, Ariane; Renner, Ellen; Minard-Colin, Véronique; Ouachée, Marie; Casanova, Jean-Laurent

2005-01-01

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

Common variable immunodeficiency: a review  

Microsoft Academic Search

Common variable immunodeficiency (CVID) is the commonest symptomatic primary antibody deficiency syndrome. The predominant manifestation is hypogammaglobulinemia. CVID is characterized by recurrent bacterial infections, especially of the upper and lower respiratory airways, and is also associated with an increased incidence of autoimmune and neoplastic disorders. Most patients are diagnosed as adults and delay in the recognition of the disease is

M. Di Renzo; A. L. Pasqui; A. Auteri

2004-01-01

89

TXU (Anti-CD7)-Pokeweed Antiviral Protein as a Potent Inhibitor of Human Immunodeficiency Virus  

PubMed Central

We have evaluated the clinical potential of TXU (anti-CD7)-pokeweed antiviral protein (PAP) immunoconjugate (TXU-PAP) as a new biotherapeutic anti-human immunodeficiency virus (anti-HIV) agent by evaluating its anti-HIV type 1 (anti-HIV-1) activity in vitro, as well as in a surrogate human peripheral blood lymphocyte-severe combined immunodeficient (Hu-PBL-SCID) mouse model of human AIDS. The present report documents in a side-by-side comparison the superior in vitro anti-HIV-1 activity of TXU-PAP compared to the activities of zidovudine, 2?,3?-didehydro-2?,3?-dideoxythymidine, unconjugated PAP, and B53-PAP, an anti-CD4-PAP immunoconjugate. Notably, TXU-PAP elicited potent anti-HIV activity in the Hu-PBL-SCID mouse model of human AIDS without any side effects and at doses that were very well tolerated by cynomolgus monkeys. Furthermore, plasma samples from TXU-PAP-treated cynomolgus monkeys showed potent anti-HIV-1 activity in vitro. PMID:9527790

Uckun, Fatih M.; Chelstrom, Lisa M.; Tuel-Ahlgren, Lisa; Dibirdik, Ilker; Irvin, James D.; Langlie, Mridula-Chandan; Myers, Dorothea E.

1998-01-01

90

A quadrivalent HPV vaccine induces humoral and cellular immune responses in WHIM immunodeficiency syndrome.  

PubMed

WHIM-syndrome is an inherited immunodeficiency disorder with abnormal susceptibility to human papillomavirus (HPV) infection and diseases. We determined safety and immunogenicity to a quadrivalent HPV vaccine in WHIM-syndrome by detection of HPV-specific antibodies and lymphoproliferation. In virus-like-particle (VLP)-ELISA, a WHIM patient showed antibody titers up to 400 for HPV-6/11/16/18, whereas immuno-competent controls developed titers of 6400-25,600. In pseudovirion assays, the patient's neutralization titers ranged from 20 to 400 to the four HPV vaccine types, while titers of 1600-25,600 were detected in healthy vaccinees. Specific proliferation of PBMC of the WHIM patient to the HPV vaccine was demonstrated. This first report on response to HPV vaccination in WHIM-immunodeficiency highlights that patients with WHIM-syndrome, and probably other immunodeficiencies, may benefit from HPV immunoprophylaxis. PMID:20472031

Handisurya, Alessandra; Schellenbacher, Christina; Reininger, Bärbel; Koszik, Frieder; Vyhnanek, Philipp; Heitger, Andreas; Kirnbauer, Reinhard; Förster-Waldl, Elisabeth

2010-07-01

91

Autoimmunity in common variable immunodeficiency  

Microsoft Academic Search

Common variable immunodeficiency (CVID) is the most common clinically significant primary immune defect. Although the hallmark\\u000a of CVID is hypogammaglobulinemia, the intrinsic dysregulation of the immune system leads to defective T-cell activation and\\u000a proliferation, as well as dendritic cell and cytokine defects. Although 70% to 80% of patients have had recurrent sinopulmonary\\u000a infections, autoimmunity and inflammatory complications are also common.

Shradha Agarwal; Charlotte Cunningham-Rundles

2009-01-01

92

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 ...

93

Gastroesophageal reflux and severe combined immunodeficiency  

Microsoft Academic Search

Background: Gastrointestinal and respiratory symptoms and failure to thrive not associated with infections or medications were noted in patients with severe combined immunodeficiency. Objective: The aim of our study was to determine the frequency of gastroesophageal reflux in patients with severe combined immunodeficiency. Methods: We studied the case histories of 73 pediatric patients who had been treated at Duke University

Andreas Boeck; Rebecca H. Buckley; Richard I. Schiff

1997-01-01

94

Evolutionarily Conserved Epitopes on Human Immunodeficiency Virus Type 1 (HIV-1) and Feline Immunodeficiency Virus Reverse Transcriptases Detected by HIV-1-Infected Subjects  

PubMed Central

Anti-human immunodeficiency virus (HIV) cytotoxic T lymphocyte (CTL)-associated epitopes, evolutionarily conserved on both HIV type 1 (HIV-1) and feline immunodeficiency virus (FIV) reverse transcriptases (RT), were identified using gamma interferon (IFN-?) enzyme-linked immunosorbent spot (ELISpot) and carboxyfluorescein diacetate succinimide ester (CFSE) proliferation assays followed by CTL-associated cytotoxin analysis. The peripheral blood mononuclear cells (PBMC) or T cells from HIV-1-seropositive (HIV+) subjects were stimulated with overlapping RT peptide pools. The PBMC from the HIV+ subjects had more robust IFN-? responses to the HIV-1 peptide pools than to the FIV peptide pools, except for peptide-pool F3. In contrast, much higher and more frequent CD8+ T-cell proliferation responses were observed with the FIV peptide pools than with the HIV peptide pools. HIV-1-seronegative subjects had no proliferation or IFN-? responses to the HIV and FIV peptide pools. A total of 24% (40 of 166) of the IFN-? responses to HIV pools and 43% (23 of 53) of the CD8+ T-cell proliferation responses also correlated to responses to their counterpart FIV pools. Thus, more evolutionarily conserved functional epitopes were identified by T-cell proliferation than by IFN-? responses. In the HIV+ subjects, peptide-pool F3, but not the HIV H3 counterpart, induced the most IFN-? and proliferation responses. These reactions to peptide-pool F3 were highly reproducible and persisted over the 1 to 2 years of testing. All five individual peptides and epitopes of peptide-pool F3 induced IFN-? and/or proliferation responses in addition to inducing CTL-associated cytotoxin responses (perforin, granzyme A, granzyme B). The epitopes inducing polyfunctional T-cell activities were highly conserved among human, simian, feline, and ungulate lentiviruses, which indicated that these epitopes are evolutionarily conserved. These results suggest that FIV peptides could be used in an HIV-1 vaccine. PMID:23824804

Sanou, Missa P.; Roff, Shannon R.; Mennella, Antony; Sleasman, John W.; Rathore, Mobeen H.; Levy, Jay A.

2013-01-01

95

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

96

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

97

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

98

Relationship of immunodeficiency to lymphoid malignancy.  

PubMed

Individuals with either primary or secondary immunodeficiencies are at high risk to develop not only infections but also malignancy (especially of the lymphoid system). The major focus of this paper is on malignancies that develop in immunodeficiency syndromes, particularly malignancies in naturally occurring immunodeficiencies and following bone marrow transplantation (BMT). As of August, 1986, 514 cases of naturally occurring immunodeficiencies have been registered at the Immunodeficiency Cancer Registry. Overall non-Hodgkin's lymphomas predominate in these patients, accounting for 48.6% of all cases. Non-Hodgkin's lymphoma is the predominant malignancy in ataxia-telangiectasia, common variable immunodeficiency, Wiskott-Aldrich syndrome (WAS) and severe combined immunodeficiency (SCID). The histopathology of the lymphomas differs somewhat in each of the disorders. In WAS, large cell "histiocytic" lymphoma predominates, with most cases having the features of B lymphocytes, including pleomorphic immunocytoma and immunoblastic lymphoma. Non-Hodgkin's lymphoma in SCID also generally has B cell features and in some cases multiple copies of Epstein-Barr virus (EBV) genomic DNA have been found in tumor tissue. In contrast to ataxia-telangiectasia, in which non-Hodgkin's lymphoma is also the predominant neoplasm, the morphology and cell marker characteristics are more similar to those seen in nonimmunodeficient children. The lymphomas in ataxia-telangiectasia are very heterogeneous with representation from all the major histologic subtypes. We have found no relationship between the degree of immunodeficiency and the development of malignancy. Immunodeficiency following BMT, as in naturally occurring immunodeficiencies, appears to predispose patients to the development of lymphoid malignancy, especially for recipients of partially mismatched bone marrow. In Minnesota 8 patients have developed B cell lympho-proliferative disorders (BLPD) following BMT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2840629

Kersey, J H; Shapiro, R S; Filipovich, A H

1988-05-01

99

Acquired immunodeficiency syndrome in Romania.  

PubMed

After the initial description of acquired immunodeficiency syndrome (AIDS) in Romania in late 1989, national AIDS case surveillance was established with a modified version of the World Health Organisation (WHO) clinical case definition. This modified case definition requires that AIDS cases have both clinical and serological evidence of human immunodeficiency virus (HIV) infection. Before December, 1989, Romania had reported 13 AIDS cases to WHO. By Dec 31, 1990, 1168 AIDS cases were reported to Romania's Ministry of Health, of which 1094 (93.7%) occurred in children less than 13 years of age at diagnosis. Of these, 1086 (99.3%) were in infants and children less than 4 years of age, and 683 (62.4%) in abandoned children living in public institutions at the time of diagnosis. By Dec 31, 1990, 493 (45.1%) mothers of children with AIDS had been located and tested, and 37 (7.5%) were positive for HIV; 423 (38.7%) cases were in children who had received transfusions of unscreened blood, and 6 (0.5%) were in children with clotting disorders. HIV transmission through the improper use of needles and syringes is strongly suspected in most of the remaining 628 (57.4%) children with AIDS, most of whom had received multiple therapeutic injections. This outbreak demonstrates the serious potential for HIV transmission in medical facilities that intensively and improperly use parenteral therapy and have poor sterilisation technique. PMID:1679471

Hersh, B S; Popovici, F; Apetrei, R C; Zolotusca, L; Beldescu, N; Calomfirescu, A; Jezek, Z; Oxtoby, M J; Gromyko, A; Heymann, D L

1991-09-14

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

TH17 Cells in Autoimmunity and Immunodeficiency: Protective or Pathogenic?  

PubMed Central

In 2005 a newly discovered T helper cell subset that secreted interleukin (IL)-17 became the center of attention in immunology. Initial studies painted Th17 cells as the culprit for destruction in many different autoimmune and auto-inflammatory diseases. Subsequently, the discovery of patients with primary immunodeficiencies in the IL-17 pathway taught us that Th17 cells have a critical role in defense against certain fungal and bacterial infections. Moreover, the paradoxical exacerbation of Crohn’s disease in the clinical trials of a Secukinumab (AIN457), a fully human neutralizing antibody to IL-17A, has cast into doubt a universal pro-inflammatory and harmful role for Th17 cells. Evidence now suggests that depending on the environment Th17 cells can alter their differentiation program, ultimately giving rise to either protective or pro-inflammatory cells. In this review we will summarize the evidence from patients with immunodeficiencies, autoimmune, or auto-inflammatory diseases that teaches us how the pro-inflammatory versus protective function of Th17 cells varies within the context of different human diseases. PMID:22675324

Marwaha, Ashish K.; Leung, Nicole J.; McMurchy, Alicia N.; Levings, Megan K.

2012-01-01

102

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

103

Cetuximab in combination with anti-human IgG antibodies efficiently down-regulates the EGF receptor by macropinocytosis  

SciTech Connect

The monoclonal antibody C225 (Cetuximab) blocks binding of ligand to the epidermal growth factor receptor (EGFR). In addition, it is known that incubation with C225 induces endocytosis of the EGFR. This endocytosis has previously been shown to be increased when C225 is combined with an additional monoclonal anti-EGFR antibody. However, the effects of antibody combinations on EGFR activation, endocytosis, trafficking and degradation have been unclear. By binding a secondary antibody to the C225-EGFR complex, we here demonstrate that a combination of antibodies can efficiently internalize and degrade the EGFR. Although the combination of antibodies activated the EGFR kinase and induced ubiquitination of the EGFR, the kinase activity was not required for internalization of the EGFR. In contrast to EGF-induced EGFR down-regulation, the antibody combination efficiently degraded the EGFR without initiating downstream proliferative signaling. The antibody-induced internalization of EGFR was found not to depend on clathrin and/or dynamin, but depended on actin polymerization, suggesting induction of macropinocytosis. Macropinocytosis may cause internalization of large membrane areas, and this could explain the highly efficient internalization of the EGFR induced by combination of antibodies. -- Highlight: Black-Right-Pointing-Pointer Cetuximab induced endocytosis of EGFR increases upon combination with anti-human IgG. Black-Right-Pointing-Pointer Antibody combination causes internalization of EGFR by macropinocytosis. Black-Right-Pointing-Pointer Antibody-induced internalization of EGFR is independent of EGFR kinase activity. Black-Right-Pointing-Pointer Antibody combination may have a zipper effect and cross-link EGFRs on neighboring cells.

Berger, Christian [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway)] [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway); Madshus, Inger Helene [Institute of Pathology, University of Oslo, Rikshospitalet, 0027 Oslo (Norway) [Institute of Pathology, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway); Stang, Espen, E-mail: espsta@rr-research.no [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway)] [Department of Pathology, Oslo University Hospital, Rikshospitalet, Post box 4950 Nydalen, 0424 Oslo (Norway)

2012-12-10

104

Pediatric human immunodeficiency virus infection.  

PubMed Central

In the past decade, an increase in pediatric human immunodeficiency virus (HIV) infection has had a substantial impact on childhood morbidity and mortality worldwide. The vertical transmission of HIV from mother to infant accounts for the vast majority of these cases. Identification of HIV-infected pregnant women needs to be impoved so that appropriate therapy can be initiated for both mothers and infants. While recent data demonstrate a dramatic decrease in HIV transmission from a subset of women treated with zidovudine during pregnancy, further efforts at reducing transmission are desperately needed. This review focuses on vertically transmitted HIV infection in children, its epidemiology, diagnostic criteria, natural history, and clinical manifestations including infectious and noninfectious complications. An overview of the complex medical management of these children ensues, including the use of antiretroviral therapy. Opportunistic infection prophylaxis is reviewed, along with the important role of other supportive therapies. PMID:8894346

Domachowske, J B

1996-01-01

105

Gene Therapy for Primary Immunodeficiencies  

PubMed Central

Abstract For over 40 years, primary immunodeficiencies (PIDs) have featured prominently in the development and refinement of human allogeneic hematopoietic stem cell transplantation. More recently, ex vivo somatic gene therapy using autologous cells has provided remarkable evidence of clinical efficacy in patients without HLA-matched stem cell donors and in whom toxicity of allogeneic procedures is likely to be high. Together with improved preclinical models, a wealth of information has accumulated that has allowed development of safer, more sophisticated technologies and protocols that are applicable to a much broader range of diseases. In this review we summarize the status of these gene therapy trials and discuss the emerging application of similar strategies to other PIDs. PMID:22691036

Rivat, Christine; Santilli, Giorgia; Gaspar, H. Bobby

2012-01-01

106

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

Federal Register 2010, 2011, 2012, 2013

...Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately Affected...Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately Affected...Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately...

2010-08-19

107

21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.  

Code of Federal Regulations, 2012 CFR

... false Human immunodeficiency virus (HIV) âlookbackâ requirements. 610.46...610.46 Human immunodeficiency virus (HIV) “lookback” requirements. ...evidence of human immunodeficiency virus (HIV) infection when tested under §...

2012-04-01

108

21 CFR 610.46 - Human immunodeficiency virus (HIV) “lookback” requirements.  

Code of Federal Regulations, 2013 CFR

... false Human immunodeficiency virus (HIV) âlookbackâ requirements. 610.46...610.46 Human immunodeficiency virus (HIV) “lookback” requirements. ...evidence of human immunodeficiency virus (HIV) infection when tested under §...

2013-04-01

109

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

110

Immunodeficiencies and Immunome: Diseases and Information Services  

Microsoft Academic Search

Essential human immunome is composed of about 900 genes and proteins. Primary immunodeficiencies (IDs) are a large and heterogenic\\u000a group of inherited disorders of the immune system. Since defects in any part of the adaptive or innate immune system can cause\\u000a disorders, numerous IDs have been detected. Immunodeficiency patients have increased susceptibility to recurrent and persistent,\\u000a even life-threatening infections. Other

Mauno Vihinen

111

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

112

The genome of feline immunodeficiency virus  

Microsoft Academic Search

Summary Feline immunodeficiency virus (FIV) is a member of the genusLentivirus of the familyRetroviridae. FIV can infect T lymphocytes and monocytes\\/macrophages in vitro and in vivo, and causes an acquired immunodeficiency syndrome-like disease in cats. Several isolates of FIV from geographically distant countries have been molecularly cloned. There is considerable heterogeneity especially in Env gene among the FIV isolates and

T. Miyazawa; K. Tomonaga; Y. Kawaguchi; T. Mikami

1994-01-01

113

Common variable immunodeficiency and the gastrointestinal tract  

Microsoft Academic Search

Common variable immunodeficiency (CVID) is the second most prevalent primary immunodeficiency disorder but clinically the\\u000a most important. It causes a wide spectrum of symptoms and signs affecting many systems of the body. CVID is a combination\\u000a of humoral and cell-mediated deficiency, which explains not only why so many systems are affected but also why standard therapy\\u000a in the form of

Ishaan Kalha; Joseph H. Sellin

2004-01-01

114

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

115

Natural killer cell inhibits human immunodeficiency virus replication in chronically infected immune cells.  

PubMed

Natural killer (NK) cells are a crucial component of the host innate immune system. We investigated the noncytolytic anti-human immunodeficiency virus (HIV) activity of NK cells in chronically HIV-infected immune cells. Supernatants collected from NK cell cultures (both primary NK cells and NK cell lines, YTS and NK 92) inhibited HIV activation in peripheral blood mononuclear cells (PBMCs) from HIV-infected subjects. NK supernatants (NK SN) also suppressed tumor necrosis factor (TNF)-alpha-induced HIV activation in chronically infected cell lines (U1 and ACH-2 cells). The antibody to interferon (IFN)-gamma blocked NK SN-mediated anti-HIV effect, while the antibodies to CC-chemokines had no impact on NK SN-mediated HIV inhibition in U1 and ACH-2 cells. Investigation of mechanism(s) responsible for the NK action showed that NK SN inhibited TNF-alpha-mediated activation of HIV-long-terminal repeat (LTR), and upregulated the expression of signal transducer and activator of transcription (STAT)-1 and phosphorylated P38 mitogen-activated protein kinase (MAPK). The P38 MAPK inhibitor (SB 203580) blocked NK SN-mediated HIV inhibition. These data provide compelling evidence that NK cells have a critical role in controlling HIV activation in the reservoirs. PMID:16997390

Zhang, Ting; Li, Yuan; Wang, Yan-Jian; Wang, Xu; Young, Mike; Douglas, Steven D; Ho, Wen-Zhe

2007-02-01

116

Alopecia areata and vitiligo as primary presentations in a young male with human immunodeficiency virus.  

PubMed

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

2014-03-01

117

Association of Non-Acquired Immunodeficiency Syndrome-Defining Cancers With Human Immunodeficiency Virus Infection  

Microsoft Academic Search

Kaposi's sarcoma and non-Hodgkin's lymphoma were among the earliest recognized manifestations of the acquired immunodeficiency syndrome (AIDS) epidemic. Excluding these two tumors, the overall risk of all other cancers in human immunodeficiency virus (HIV)-infected individuals is similar to that of the general population. However, varying levels of evidence link several additional neoplasms to HIV infection. The evidence is strongest for

Charles S. Rabkin

118

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

119

Neutralizing Acids and Bases  

NSDL National Science Digital Library

In this activity, students will 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. This website includes a student activity sheet and additional student readings.

2010-01-01

120

ITER neutralizer modeling (abstract)  

SciTech Connect

In the neutralizer of the ITER Neutral Beam Injector, a 1 MeV-D{sup -} beam passes through an structure filled with D{sub 2} gas, where negative ions are mainly converted to fast D{sup 0} atoms. Once that the beam is neutralized no further optical correction is possible, i.e., transport from the neutralizer to the confinement chamber is ballistic. Because of this, the transport through the neutralizer determines ultimately the geometrical properties of the neutral beams. The ionization of the buffer gas (D{sub 2}) filling the neutralizer induced by the D beam creates a rarefied and low temperature plasma (ionization degree {approx_equal}10{sup -3}, electron temperature {approx_equal}20 eV). This plasma can screen the electrostatic well of the D beam and, consequently, affect the properties of the extracted beam and the energy transport to the neutralizer walls. On the other hand, the plasma will eventually escape from the neutralizer and move back in the accelerator chain, toward the accelerating grids and the source. We present particle-in-cell simulations of the beam propagation and plasma formation through the neutralizer. Particle-particle and particle-wall collisions are treated using a Monte Carlo approach. Simulations show that the secondary plasma effectively screens the beam space charge preventing beam radial expansion due to Coulomb repulsion between beam ions. First results suggest that the current of plasma ions (D{sub 2}{sup +}) into the accelerator would be of the order of I(D{sup -})/100, with I(D{sup -}) the negative ion current.

Minea, T.; Lifschitz, A.; Maynard, G.; Katsonis, K.; Bretagne, J.; Simonin, A. [Laboratoire de Physique des Gaz et des Plasmas, Universite Paris Sud XI, 91405 Orsay Cedex (France); DRFC, CEA Cadarache, 13108 Saint-Paul lez Durance (France)

2008-02-15

121

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) ...

122

Adult-onset immunodeficiency in Thailand and Taiwan  

PubMed Central

Background Autoantibodies against interferon-? are associated with severe disseminated opportunistic infection, but their importance and prevalence are unknown. Methods We enrolled 203 persons from sites in Thailand and Taiwan in five groups: 52 patients with disseminated, rapidly or slowly growing, nontuberculous mycobacterial infection (group 1); 45 patients with another opportunistic infection, with or without nontuberculous mycobacterial infection (group 2); 9 patients with disseminated tuberculosis (group 3); 49 patients with pulmonary tuberculosis (group 4); and 48 healthy controls (group 5). Clinical histories were recorded, and blood specimens were obtained. Results Patients in groups 1 and 2 had CD4+ T-lymphocyte counts that were similar to those in patients in groups 4 and 5, and they were not infected with the human immunodeficiency virus (HIV). Washed cells obtained from patients in groups 1 and 2 had intact cytokine production and a response to cytokine stimulation. In contrast, plasma obtained from these patients inhibited the activity of interferon-? in normal cells. High-titer anti–interferon-? autoantibodies were detected in 81% of patients in group 1, 96% of patients in group 2, 11% of patients in group 3, 2% of patients in group 4, and 2% of controls (group 5). Forty other anti-cytokine autoantibodies were assayed. One patient with cryptococcal meningitis had autoantibodies only against granulocyte–macrophage colony-stimulating factor. No other anti-cytokine autoantibodies or genetic defects correlated with infections. There was no familial clustering. Conclusions Neutralizing anti–interferon-? autoantibodies were detected in 88% of Asian adults with multiple opportunistic infections and were associated with an adult-onset immunodeficiency akin to that of advanced HIV infection. PMID:22913682

Browne, Sarah K.; Burbelo, Peter D.; Chetchotisakd, Ploenchan; Suputtamongkol, Yupin; Kiertiburanakul, Sasisopin; Shaw, Pamela A.; Kirk, Jennifer L.; Jutivorakool, Kamonwan; Zaman, Rifat; Ding, Li; Hsu, Amy P.; Patel, Smita Y.; Olivier, Kenneth N.; Lulitanond, Viraphong; Mootsikapun, Piroon; Anunnatsiri, Siriluck; Angkasekwinai, Nasikarn; Sathapatayavongs, Boonmee; Hsueh, Po-Ren; Shieh, Chi-Chang; Brown, Margaret R.; Thongnoppakhun, Wanna; Claypool, Reginald; Sampaio, Elizabeth P.; Thepthai, Charin; Waywa, Duangdao; Dacombe, Camilla; Reizes, Yona; Zelazny, Adrian M.; Saleeb, Paul; Rosen, Lindsey B.; Mo, Allen; Iadarola, Michael; Holland, Steven M.

2014-01-01

123

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

124

[Common variable immunodeficiency: a clinical challenge].  

PubMed

Common variable immunodeficiency (CVID) represents the most common clinically relevant form of primary immunodeficiency. This heterogeneous antibody deficiency syndrome is characterized not only by susceptibility to bacterial respiratory tract infections but displays additional signs of immune dysregulation, such as autoimmunity, chronic inflammation and lymphoproliferation in more than 30?% of the patients. Due to poor awareness the diagnosis is often delayed by 4-6 years. A close collaboration in patient care with a center specialized in primary immunodeficiency is recommended. Regular follow-up visits include assessment of adequate immunoglobulin replacement therapy and screening for manifestation of secondary complications. Regular substitution with intravenous or subcutaneous immunoglobulins has more or less normalized life expectancy of patients with isolated susceptibility to bacterial infections. Therefore, the current core task in the management of CVID patients is the elaboration of more effective and safer forms of prophylaxis and treatment of sequelae of immune dysregulation in the lungs, intestines and liver of affected patients. PMID:23929240

Warnatz, K; Goldacker, S

2013-09-01

125

The association between immunodeficiency and congenital heart disease  

Microsoft Academic Search

Summary The predilection of children with congenital heart disease (CHD) to infection may be explained in part by an underlying immunodeficiency disorder. Some 13 syndromes in which immunodeficiency and CHD may coexist have been reported in the medical literature. In addition, immunoglobulin and T-cell deficiencies have been found in nonsyndromal patients with CHD. The diagnosis of immunodeficiency should be entertained

Dorothy J. Radford; Y. H. Thong

1988-01-01

126

Functional Pseudotyping of Human Immunodeficiency Virus Type 1 Vectors by Western Equine Encephalitis Virus Envelope Glycoprotein ?  

PubMed Central

We investigated the ability of western equine encephalitis virus envelope glycoproteins (WEEV GP) to pseudotype lentiviral vectors. The titers of WEEV GP-pseudotyped human immunodeficiency virus type 1 (HIV) ranged as high as 8.0 × 104 IU/ml on permissive cells. Sera from WEEV-infected mice specifically neutralized these pseudotypes; cell transduction was also sensitive to changes in pH. The host range of the pseudotyped particles in vitro was somewhat limited, which is atypical for most alphaviruses. HIV vectors pseudotyped by WEEV GP may be a useful tool for characterizing WEEV cell binding and entry and screening for small-molecule inhibitors. PMID:18842711

Poluri, Ananthalakshmi; Ainsworth, Rebecca; Weaver, Scott C.; Sutton, Richard E.

2008-01-01

127

Anti-human IG and B lymphocytes reconstitute the proliferative response to Con A of T lymphocytes depleted of accessory cells  

SciTech Connect

The requirements for the induction of proliferation of human peripheral blood mononuclear cells (PBM) by low concentrations of Concanavalin A (Con A) were studied using /sup 3/H-thymidine incorporation to assay DNA synthesis. Removal of plastic-adherent cells from PBM reduced the proliferative response of lymphocytes to Con A by 80%. Passage of these cells over nylon wool columns totally eliminated their response to Con A. Addition of adherent monocytes or rabbit anti-human IgG conjugated to polyacrylamide beads (anti-IgG beads) to the non-adherent lymphocyte population reconstituted the proliferative response. The lymphoblasts activated in these cultures were more than 90% T11 positive. Anti-IgG beads did not activate lymphocyte proliferation in the absence of Con A. The response of non-adherent lymphocytes to Con A could also be reconstituted by unconjugated rabbit anti-human IgG antiserium. Purified T cells could only be activated by anti-IgG beads and low concentrations of Con A in the presence of irradiated B cells. These results suggest that /sup 3/H-thymidine incorporation by T cells induced by anti-IgG beads and a low concentration of Con A depends on the interaction of anti-IgG and B cells. The authors suggest that B cell produce growth factors for T cells after interacting with anti-IgG.

Tsuda, T.; Kim, Y.T.; Schwab, R.; Siskind, G.W.; Weksler, M.E.

1986-03-01

128

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

PubMed

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

2014-08-01

129

78 FR 46969 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...  

Federal Register 2010, 2011, 2012, 2013

...meeting entitled ``Human Immunodeficiency Virus (HIV) Patient-Focused Drug Development and HIV Cure Research,'' published in the Federal Register...perspective on current approaches to managing HIV, symptoms experienced because of HIV or its...

2013-08-02

130

78 FR 29755 - Human Immunodeficiency Virus Patient-Focused Drug Development and Human Immunodeficiency Virus...  

Federal Register 2010, 2011, 2012, 2013

...public comment on human immunodeficiency virus (HIV) Patient-Focused Drug Development and HIV Cure Research. Patient-Focused Drug Development...interested in obtaining patient input on the impact of HIV on daily life, available therapies to treat...

2013-05-21

131

Policy on Gender Neutral Housing Policy on Gender-Neutral  

E-print Network

Policy on Gender Neutral Housing 10/01/2013 Policy on Gender-Neutral Housing I. Purpose and Scope Gender-neutral housing gives students the option to reside with another student, regardless of sex, gender, gender identity or gender expression. II. Definitions Gender-neutral housing is defined

Sridhar, Srinivas

132

Women at Risk for Human Immunodeficiency Virus  

Microsoft Academic Search

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 HIV infection. The

David Quadagno; Dianne F. Harrison; K. G. Wambach; Philippa Levine; Allen Imershein; Joseph Byers; Kim Maddox

1992-01-01

133

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

134

Mutation pattern of human immunodeficiency virus genes  

Microsoft Academic Search

Summary Human immunodeficiency viruses (HIVs) show extensive genetic variation. This feature is the fundamental cause of pathogenicity of HIVs and thwarts efforts to develop effective vaccines. To understand the mutation mechanism of these viruses, we analyzed nucleotide sequences ofenv andgag genes of the viruses by use of molecular evolutionary methods and estimated the direction and frequency of nucleotide substitutions. Results

Etsuko N. Moriyama; Yasuo Ina; Kazuho Ikeo; Nobuaki Shimizu; Takashi Gojobori

1991-01-01

135

The Epidemiology of Human Immunodeficiency Virus Infection.  

ERIC Educational Resources Information Center

Reviews epidemiology and natural history of human immunodeficiency virus-Type 1 (HIV-1) infection. Discusses early and late clinical manifestations, diagnosis of infection, incubation and latency periods, and survival time. Reviews data from published literature on distribution of HIV infection in adult United States population and factors that…

Glasner, Peter D.; Kaslow, Richard A.

1990-01-01

136

Human immunodeficiency virus type 2 (HIV2).  

PubMed

In the mid 1980's a second human retrovirus, capable of causing the acquired immunodeficiency syndrome (AIDS), was isolated from patients of West African origin. This virus, now called human immunodeficiency virus type 2 (HIV2), was found to be distinct from human immunodeficiency virus type 1 (HIV1) but closely related to simian immunodeficiency viruses (SIV). Although the genomes of HIV1 and HIV2 are similar there are significant differences in nucleotide and amino acid sequences, most marked with the envelope genes and proteins. Both viruses, however, bind to the same CD4 cellular receptor. HIV2 is largely confined to West Africa where it is the dominant HIV, though patients infected with HIV2 have been described in Europe and America. Its transmission, clinical features and immunological effects are similar to those associated with HIV1 infection. However, there is some suggestion that the incubation period from infection to clinical disease may be longer than with HIV1 and that HIV2 may be less pathogenic. Patients with sera that react with both HIV1 and HIV2 antigens have been described, but it is unclear whether this represents serological cross reactivity or true double virus infection. Testing for HIV2 antibodies may become increasingly necessary in HIV2 non-endemic areas. PMID:2245251

Hughes, A; Corrah, T

1990-09-01

137

Common Variable Immunodeficiency: Etiological and Treatment Issues  

Microsoft Academic Search

One of the great advances in clinical medicine was the recognition of the pleomorphism of the immune response and the multiple afferent and efferent limbs of antigen processing and responsiveness. A significant contribution to this understanding was derived from studies of human immunodeficiency states, including both inherited and acquired syndromes. Amongst these syndromes, one of the most common, and least

Sean Deane; Carlo Selmi; Suzanne S. Teuber; M. Eric Gershwin

2009-01-01

138

Rectosigmoidal colitis in common variable immunodeficiency disease  

Microsoft Academic Search

Summary A patient with common variable immuno-deficiency disease is described with severe colitis confined to the rectosigmoid region. Inflammation was extensive in the regions involved and exhibited a character that we believe is most unusual. Inflammation was transmural in the regions involved. Macrophages were the major inflammatory cells, and no granulomas or giant cells were seen. Although the disorder seemed

Ronald G. Strauss; Fayez Ghishan; Frank Mitros; John R. Ebensberger; C. Thomas Kisker; Raymond Tannous; M. Kabir Younoszai

1980-01-01

139

The Neutral Medium  

E-print Network

We consider the physical conditions of the neutral medium within, and in the environments of, galaxies. The basic physical and morphological properties of the neutral medium within galaxy disks are now quite well-constrained. Systematic variations in temperature and phase-balance (of cool versus warm neutral gas) are indicated as a function of both radius and z-height. Interestingly, the cool medium line-widths are observed to be dominated by turbulent energy injection within cells of 10 pc to 1 kpc size. Deep new observations reveal that 5-10% of the neutral medium is associated within an extended halo which rotates more slowly and experiences radial inflow. Much of this component is likely to be associated with a ``galactic fountain'' type of phenomenon. However, compelling evidence is also accumulating for the importance of tidal disruption of satellites as well as continuous accretion (of both diffuse and discrete components) in fueling galaxy halos and disks. Continued fueling is even observed on scales of 100's of kpc in galaxy environments, where the neutral component is likely to be merely a trace constituent of a highly ionized plasma.

Robert Braun

2005-01-17

140

Ultracold neutral plasmas.  

PubMed

Ultracold neutral plasmas occupy an exotic regime of plasma physics in which electrons form a swarming, neutralizing background for ions that sluggishly move in a correlated manner. Strong interactions between the charged particles give rise to surprising dynamics such as oscillations of the average kinetic energy during equilibration and extremely fast recombination. Such phenomena offer stimulating and challenging problems for computational scientists, and the physics can be applied to other environments, such as the interior of gas giant planets and plasmas created by short-pulse laser irradiation of solid, liquid, and cluster targets. PMID:17478712

Killian, Thomas C

2007-05-01

141

Protection in Macaques Immunized with HIV-1 Candidate Vaccines Can Be Predicted Using the Kinetics of Their Neutralizing Antibodies  

PubMed Central

Background A vaccine is needed to control the spread of human immunodeficiency virus type 1 (HIV-1). An in vitro assay that can predict the protection induced by a vaccine would facilitate the development of such a vaccine. A potential candidate would be an assay to quantify neutralization of HIV-1. Methods and Findings We have used sera from rhesus macaques that have been immunized with HIV candidate vaccines and subsequently challenged with simian human immunodeficiency virus (SHIV). We compared neutralization assays with different formats. In experiments with the standardized and validated TZMbl assay, neutralizing antibody titers against homologous SHIVSF162P4 pseudovirus gave a variable correlation with reductions in plasma viremia levels. The target cells used in the assays are not just passive indicators of virus infection but are actively involved in the neutralization process. When replicating virus was used with GHOST cell assays, events during the absorption phase, as well as the incubation phase, determine the level of neutralization. Sera that are associated with protection have properties that are closest to the traditional concept of neutralization: the concentration of antibody present during the absorption phase has no effect on the inactivation rate. In GHOST assays, events during the absorption phase may inactivate a fixed number, rather than a proportion, of virus so that while complete neutralization can be obtained, it can only be found at low doses particularly with isolates that are relatively resistant to neutralization. Conclusions Two scenarios have the potential to predict protection by neutralizing antibodies at concentrations that can be induced by vaccination: antibodies that have properties close to the traditional concept of neutralization may protect against a range of challenge doses of neutralization sensitive HIV isolates; a window of opportunity also exists for protection against isolates that are more resistant to neutralization but only at low challenge doses. PMID:22216149

Davis, David; Koornstra, Wim; Mortier, Daniella; Fagrouch, Zahra; Verschoor, Ernst J.; Heeney, Jonathan L.; Bogers, Willy M. J. M.

2011-01-01

142

Lymphocyte subset reconstitution patterns in children with small bowel transplantation induced with steroid-free rabbit anti-human thymocyte globulin.  

PubMed

Multiple measurements (n = 212) of lymphocyte subsets in 67 children treated with steroid-free Tacrolimus, and rabbit anti-human thymocyte globulin induction demonstrate early reconstitution of T-cytotoxic and NK cells. Reconstitution of CD4+ cells is complete after the second post-transplant year. During the period at risk for rejection, NK and T-cytotoxic cell counts are significantly higher among Rejectors. During periods at increased risk for EBV viral infection, CD4 counts bear a significant inverse relationship to EBV viral load in a subset of at-risk recipients. Rejection-prone children also demonstrate significantly higher counts of total lymphocytes, Tc and NK cells prior to SBTx, and may illustrate one basis for enhanced baseline immunocompetence. PMID:18785909

Talukdar, Anjan J; Ashokkumar, Chethan; Wilson, Patrick; Gupta, Ankit; Sun, Qing; Boig, Linda; Abu-Elmagd, Kareem; Mazariegos, George; Green, Michael; Sindhi, Rakesh

2009-05-01

143

Adeno-Associated Virus 9-Mediated Airway Expression of Antibody Protects Old and Immunodeficient Mice against Influenza Virus.  

PubMed

Influenza causes serious and sometimes fatal disease in individuals at risk due to advanced age or immunodeficiencies. Despite progress in the development of seasonal influenza vaccines, vaccine efficacy in elderly and immunocompromised individuals remains low. We recently developed a passive immunization strategy using an adeno-associated virus (AAV) vector to deliver a neutralizing anti-influenza antibody at the site of infection, the nasal airways. Here we show that young, old, and immunodeficient (severe combined immunodeficient [SCID]) mice that were treated intranasally with AAV9 vector expressing a modified version of the broadly neutralizing anti-influenza antibody FI6 were protected and exhibited no signs of disease following an intranasal challenge with the mouse-adapted H1N1 influenza strain A/Puerto Rico/8/1934(H1N1) (PR8) (Mt. Sinai strain). Nonvaccinated mice succumbed to the PR8 challenge due to severe weight loss. We propose that airway-directed AAV9 passive immunization against airborne infectious agents may be beneficial in elderly and immunocompromised patients, for whom there still exists an unmet need for effective vaccination against influenza. PMID:25209558

Adam, Virginie S; Crosariol, Marco; Kumar, Sachin; Ge, Moyar Q; Czack, Sarah E; Roy, Soumitra; Haczku, Angela; Tretiakova, Anna; Wilson, James M; Limberis, Maria P

2014-11-01

144

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

145

Combined immunodeficiency associated with xeroderma pigmentosum.  

PubMed

We report a 15-month-old boy with xeroderma pigmentosum, a history of repeated infections, and immune deficiency who developed a fatal pneumonia with parainfluenza type 1. Immunologic evaluation revealed a severe combined immunodeficiency with hypoglobulinemia, C3 deficiency, anergic response to skin testing, and an abnormal lymphocytic response to mitogens. We suggest that patients with xeroderma pigmentosum be evaluated carefully for immune deficiencies, should repeated infections occur. PMID:2359729

Goldstein, B; Khilnani, P; Lapey, A; Cleaver, J E; Rhodes, A R

1990-06-01

146

Otitis Media in Children with Congenital Immunodeficiencies  

Microsoft Academic Search

Otitis media represents one of the most common infections in childhood. Within the first 3 years of life, up to 80% of children\\u000a experience at least one episode of otitis media. It is often resolved with supportive therapies and consequently not considered\\u000a a worrisome problem. However, it may be an early manifestation of a severe underlying disease. Primary immunodeficiencies\\u000a are rare

Simon Urschel

2010-01-01

147

Thermal inactivation of bovine immunodeficiency virus.  

PubMed Central

Cell-associated bovine immunodeficiency virus (BIV) and cell-free BIV were subjected to increasing temperatures, including pasteurization conditions. To determine the effect of heat treatment on BIV viability, reverse transcriptase activity and infectivity of the heat-treated virus were assessed. BIV was inactivated by heating to 47 degrees C for 30 min and by low- and high-temperature pasteurization conditions. PMID:8900024

Moore, E C; Keil, D; Coats, K S

1996-01-01

148

Family studies in common variable immunodeficiency.  

PubMed

The occurrence of cancer, immunodeficiency, and diseases with possible autoimmune aetiology were studied in 355 blood relatives of 12 patients with common variable immunodeficiency (CVID). The family members were identified through the patients and interviewed after completing a questionnaire, their diseases were medically confirmed by local general practitioners. In two families consanguineous marriages were identified with the coefficients of inbreeding of 0.03125 and 0.01563, respectively: one patient, a dizygotic twin of an unaffected sister, was a granddaughter of first cousins, the second patient was the third daughter of second cousins. These cases of CVID strongly support the autosomal recessivity of the underlying genes. One male patient with CVID was shown to be related to a patient with X-linked hypogammaglobulinaemia, both sharing a common carrier. The different clinical courses of their diseases suggest two genetically determined immunodeficiencies and genetic heterogeneity. No family had an unusual clustering of cancer. The occurrence of tumours in the blood relatives of CVID patients was not significantly higher than in the relatives of spouse controls. Immunological examination of 30 first degree relatives of the CVID patients revealed three children (2 males and 1 female) with selective IgA deficiency, in one boy combined with elevated serum IgE level. Four relatives with rheumatoid heart disease, 12 cases of gastric or duodenal ulcer, and 14 relatives with thyroid disease represented the most often encountered diagnoses with a possible autoimmune component in their aetiology. PMID:1880404

Vorechovský, I; Litzman, J; Lokaj, J; Sobotková, R

1991-01-01

149

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

150

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

151

Problems of Prophylaxis of Secondary Immunodeficiency States.  

PubMed

An attempt is made in this paper to draw up some results of long-term studies conducted by the "Immunoprophylaxis" Center of RANS on such studies. The results of mass and individual studies among 250 thousand blue- and white-collar workers in Russian industrial enterprises are processed in the data bank of the Center, including an analysis of the immunological reactions of 30 thousand individuals studied. An analysis of the results shows that secondary immunodeficiency is encountered in 30% of the people occupied in industrial positions, in 40% of professional athletes and in more than 60% of the children studied. It should be emphasized that in enterprises where there is substantial excessive environmental harm, the frequency of development of immunodeficiency also exceeded the 60% mark. There are many reasons for the development of immunological deficiency and they depend on a large number of factors. Among them, in the first place, is the anthropogenic effect on the environment, which results in contamination of working zones, the earth, water and, as a consequence, food products, the use of which inevitably results in immunodepression. A special place in this problem is occupied by stress, which accompanies almost any professional activity. There is no doubt concerning the opinion that normal functioning of the immune system provides a sufficiently effective "interdiction" against the development of many diseases. Immune deficiency "opens the door" to illness. In other words, immunodeficiency is a detonator for the growth of a pathology. PMID:12687143

Pershin, Boris B.; Kuzmin, Sergey N.; Medvedev, Vladimir Ya.; Tolstov, Dmitry V.

1999-12-01

152

Nonprogressive and Progressive Primate Immunodeficiency Lentivirus Infections  

PubMed Central

Natural hosts for simian immunodeficiency virus (SIV)can be, and are often naturally, infected with species-specific SIVs, but do not develop acquired immunodeficiency syndrome (AIDS). These natural hosts maintain high SIV viral loads, but avoid immunodeficiency. Elucidating the mechanisms that allow natural hosts to co-exist with SIV without overt disease may provide crucial information for understanding AIDS pathogenesis. Over the past few years, several key features of natural SIV infections have been described in studies conducted predominantly in sooty mangabeys (SMs), African green monkeys (AGMs), and mandrills. Natural SIV hosts are able to avoid the chronic, generalized immune system activation that is associated with disease progression in HIV-infected individuals and are known to down-modulate the expression of the receptors for SIV. In this perspective we propose that a critical factor that differentiates nonprogressive from progressive HIV or SIV infection is the maintenance of T cell immune competence in the face of a virus that infects and kills CD4+ T cells Elucidation of the mechanisms underlying the preservation of immune function during and after the acute phase of natural SIV infection may lead to the design of novel preventive and therapeutic interventions for treatment of chronic HIV infection. PMID:20620940

Brenchley, Jason M.; Silvestri, Guido; Douek, Daniel C.

2010-01-01

153

Nature of Nonfunctional Envelope Proteins on the Surface of Human Immunodeficiency Virus Type 1  

PubMed Central

Human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies are thought be distinguished from nonneutralizing antibodies by their ability to recognize functional gp120/gp41 envelope glycoprotein (Env) trimers. The antibody responses induced by natural HIV-1 infection or by vaccine candidates tested to date consist largely of nonneutralizing antibodies. One might have expected a more vigorous neutralizing response, particularly against virus particles that bear functional trimers. The recent surprising observation that nonneutralizing antibodies can specifically capture HIV-1 may provide a clue relating to this paradox. Specifically, it was suggested that forms of Env, to which nonneutralizing antibodies can bind, exist on virus surfaces. Here, we present evidence that HIV-1 particles bear nonfunctional gp120/gp41 monomers and gp120-depleted gp41 stumps. Using a native electrophoresis band shift assay, we show that antibody-trimer binding predicts neutralization and that the nonfunctional forms of Env may account for virus capture by nonneutralizing antibodies. We hypothesize that these nonfunctional forms of Env on particle surfaces serve to divert the antibody response, helping the virus to evade neutralization. PMID:16474158

Moore, Penny L.; Crooks, Emma T.; Porter, Lauren; Zhu, Ping; Cayanan, Charmagne S.; Grise, Henry; Corcoran, Paul; Zwick, Michael B.; Franti, Michael; Morris, Lynn; Roux, Kenneth H.; Burton, Dennis R.; Binley, James M.

2006-01-01

154

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

155

How to remain neutral: an experimental analysis of neutralization.  

PubMed

Many patients with obsessive-compulsive problems engage in neutralizing activity to reduce or "cancel out" the effects of the obsession. In many cases, neutralization is covert and therefore difficult to assess or manipulate experimentally. We hypothesize that neutralization resembles overt compulsions. In particular, it was predicted that: (i) neutralization reduces the anxiety evoked by unacceptable thoughts, and (ii) if neutralization is delayed, anxiety and the urge to neutralize will decay naturally. To test the hypothesis, 63 Ss prone to a cognitive bias known to be associated with obsessional complaints (thought-action fusion) were asked to write a sentence that would evoke anxiety. Measures of anxiety (and other variables of interest such as guilt, responsibility and the likelihood of harm) were taken. Subjects were then instructed to either immediately neutralize (n = 29) or delay for 20 min (n = 34), after which time anxiety and urge to neutralize were re-assessed. The Ss who had neutralized were then instructed to delay, and the Ss who had delayed were now instructed to neutralize, after which time the final assessments were taken. The results confirmed the predictions and supported the hypothesis that neutralization resembles overt compulsions. Of note, there were no differences between anxiety reduction after a 20-min delay, and after immediate neutralization. The problems involved in designing and conducting experiments on covert phenomena are discussed, and the clinical implications of the study are considered. PMID:8990540

Rachman, S; Shafran, R; Mitchell, D; Trant, J; Teachman, B

1996-01-01

156

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

157

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

158

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

159

Neutral Buoyancy Simulator Test  

NASA Technical Reports Server (NTRS)

A diver tests a secondary camera and maneuvering platform in Marshall's Neutral Buoyancy Simulator (NBS).The secondary camera will be beneficial for recording repairs and other extra vehicular activities (EVA) the astronuats will perform while making repairs on the Hubble Space Telescope (HST). The maneuvering platform was developed to give the astronauts something to stand on while performing maintenance tasks. These platforms were developed to be mobile so that the astronauts could move them to accommadate different sites.

1995-01-01

160

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

161

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

162

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

163

Chromosomal radiosensitivity in patients with common variable immunodeficiency  

Microsoft Academic Search

Common variable immunodeficiency (CVID) is a heterogeneous group of primary immunodeficiency disorders. In addition to recurrent infections and autoimmunity, cancers are more prevalent in these patients than the normal population. Increased radiosensitivity may be a reason for the increased malignancies. To analyze chromosomal radiosensitivity of CVID patients, lymphocytes were cultured from 20 CVID patients. After irradiation (50, 100cGy), metaphases were

Asghar Aghamohammadi; Mostafa Moin; Ali Kouhi; Mohammad-Ali Mohagheghi; Alireza Shirazi; Nima Rezaei; Sanaz Tavassoli; Mahbod Esfahani; Taher Cheraghi; Jila Dastan; Jeanet Nersesian; Saeed Reza Ghaffari

2008-01-01

164

Human cytomegalovirus infection is not increased in common variable immunodeficiency  

Microsoft Academic Search

It has been postulated that human cytomegalovirus (HCMV) infection may have a role in the pathogenesis of common variable immunodeficiency (CVID). Many patients have a lymphocyte phenotype similar to that seen in HCMV infection, HCMV mononucleosis may precipitate hypogammaglobulinaemia, and a previous small study of common variable immunodeficient patients reported a high rate of active HCMV infection. This study investigated

C. G. Mullighan; S. J. Read; A. G. Bird; J. B. Kurtz; H. M. Chapel; K. I. Welsh

1996-01-01

165

Vitamin A Deficiency in Patients with Common Variable Immunodeficiency  

Microsoft Academic Search

Vitamin A, a naturally occuring antioxidant micronutrient, has immunomodulating effect in patients with immunodeficiency, including an influence on cytokine production and lymphocyte growth and functions. Vitamin A deficiency is associated with a shift from type 2 cytokines to predominantly type 1 cytokines. The aims of this study were to determine Vitamin A status in Common variable immunodeficiency (CVID) patients and

Sara Sebnem Kilic; Esra Yapici Kezer; Yesim Ozarda Ilcol; Tahsin Yakut; Sami Aydin; Ismail Hakki Ulus

2005-01-01

166

Retinal arterial plaques in acquired immunodeficiency syndrome  

PubMed Central

The authors report the unusual observation discrete plaque like excrescencies along the retinal arterial wall in a young patient with acquired immunodeficiency syndrome. Though bilateral, in the right eye there was severe arteriolar narrowing and so these plaques were less identifiable. Fluorescein angiography did not reveal any arteriolar occlusion or areas of capillary occlusion in both eyes. There were no other signs of HIV associated microangiopathy and the patient did not have any concurrent cardiovascular or hematological abnormality. The cause of these plaques remains unexplained and we conjecture that they could represent macro immune-complex deposition along the arteriolar walls. PMID:24765430

Venkatesh, Pradeep; Pathak, Harish; Garg, Satpal

2012-01-01

167

Screening for severe combined immunodeficiency in neonates  

PubMed Central

Severe combined immunodeficiency (SCID) is a rare disease that severely affects the cellular and humoral immune systems. Patients with SCID present with recurrent or severe infections and often with chronic diarrhea and failure to thrive. The disease is uniformly fatal, making early diagnosis essential. Definitive treatment is hematopoietic stem cell transplantation, with best outcomes prior to 3.5 months of age. Newborn screening for SCID using the T-cell receptor excision circle assay has revolutionized early identification of infants with SCID or severe T-cell lymphopenia. PMID:24068875

Kelly, Brian T; Tam, Jonathan S; Verbsky, James W; Routes, John M

2013-01-01

168

Therapy of severe aplastic anemia with anti-human thymocyte globulin and androgens: the effect of HLA-haploidentical marrow infusion.  

PubMed

Fifty-four patients with severe aplastic anemia were treated with horse anti-human thymocyte globulin (ATG) and androgens. Thirty of these patients also received an infusion of HLA-haploidentical marrow cells. Only those patients having evidence of hematologic recovery within 3 mo after ATG therapy were considered responders to the immunosuppressive regimen. Of 53 patients evaluable for response, 21 had complete or partial responses and 7 had minimal improvement by defined criteria. The remaining patients did not respond or died. Factors correlated with response to therapy included a short duration of aplasia and a high admission granulocyte count. Thirty-six patients (66.7%) are surviving between 18 and 43 mo, and 18 have died. Deaths were due to hemorrhage and/or infection. Short duration of aplasia and high granulocyte counts also correlated with survival, as did younger age. Four patients with complete or partial responses had a recurrence of severe aplasia 6-17 mo after their first course of ATG. Three of these patients were retreated with ATG (and oxymetholone in two cases). All three had second responses to therapy, but two of the three have had second relapses. The fourth patient responded to oxymetholone alone, but died after a second relapse. Mismatched marrow infusion had no effect on the incidence of response or survival. PMID:6362750

Doney, K; Dahlberg, S J; Monroe, D; Storb, R; Buckner, C D; Thomas, E D

1984-02-01

169

Preparation and Characterization of Covalently Binding of Rat Anti-human IgG Monolayer on Thiol-Modified Gold Surface  

NASA Astrophysics Data System (ADS)

The 16-mercaptohexadecanoic acid (MHA) film and rat anti-human IgG protein monolayer were fabricated on gold substrates using self-assembled monolayer (SAM) method. The surface properties of the bare gold substrate, the MHA film and the protein monolayer were characterized by contact angle measurements, atomic force microscopy (AFM), grazing incidence X-ray diffraction (GIXRD) method and X-ray photoelectron spectroscopy, respectively. The contact angles of the MHA film and the protein monolayer were 18° and 12°, respectively, all being hydrophilic. AFM images show dissimilar topographic nanostructures between different surfaces, and the thickness of the MHA film and the protein monolayer was estimated to be 1.51 and 5.53 nm, respectively. The GIXRD 2? degrees of the MHA film and the protein monolayer ranged from 0° to 15°, significantly smaller than that of the bare gold surface, but the MHA film and the protein monolayer displayed very different profiles and distributions of their diffraction peaks. Moreover, the spectra of binding energy measured from these different surfaces could be well fitted with either Au4f, S2p or N1s, respectively. Taken together, these results indicate that MHA film and protein monolayer were successfully formed with homogeneous surfaces, and thus demonstrate that the SAM method is a reliable technique for fabricating protein monolayer.

Lv, Zhengjian; Wang, Jianhua; Deng, Linhong; Chen, Guoping

2009-12-01

170

Health Administrator Perspectives on Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Prevention and Services at Historically Black Colleges and Universities  

ERIC Educational Resources Information Center

Objective: Due to the disproportionate impact of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) among African American young adults, the authors explored (1) number of historically black college and university (HBCU) campuses with existing HIV prevention policies and services and (2) perceived barriers for implementing…

Warren-Jeanpiere, Lari; Jones, Sandra; Sutton, Madeline Y.

2011-01-01

171

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

172

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

173

Serum enhancement of human immunodeficiency virus (HIV) infection correlates with disease in HIV-infected individuals.  

PubMed Central

The sera from 16 individuals infected with the human immunodeficiency virus (HIV) at different clinical stages were evaluated for antibody-dependent neutralization and/or enhancement of infectivity by HIV. The HIV isolate from each individual (homotypic) and established laboratory strains showing broad cellular host range and cytopathicity were used. All sera could neutralize one of the laboratory-passaged isolates, whereas only two could neutralize the corresponding homotypic strain. Seven homotypic isolates were enhanced by serum from the respective individual. This activity was primarily observed in patients with acquired immune deficiency syndrome. Moreover, the tropism for macrophages of four of these seven viral isolates was found to be enhanced by the homotypic sera. Finally, sequential pairs of HIV and sera obtained from five HIV-infected individuals with different clinical progression were studied over time. The enhancing activity of three of the five sera appeared to increase over time, indicating changes in both the host virus population and the type of antibodies produced. These results suggest that enhancing antibodies contribute to the spread and pathogenesis of HIV in vivo. They emphasize the necessity of studying further the association of enhancing antibodies and disease progression in infected individuals. PMID:2319642

Homsy, J; Meyer, M; Levy, J A

1990-01-01

174

C-terminal tail of human immunodeficiency virus gp41: functionally rich and structurally enigmatic  

PubMed Central

The human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) pandemic is amongst the most important current worldwide public health threats. While much research has been focused on AIDS vaccines that target the surface viral envelope (Env) protein, including gp120 and the gp41 ectodomain, the C-terminal tail (CTT) of gp41 has received relatively little attention. Despite early studies highlighting the immunogenicity of a particular CTT sequence, the CTT has been classically portrayed as a type I membrane protein limited to functioning in Env trafficking and virion incorporation. Recent studies demonstrate, however, that the Env CTT has other important functions. The CTT has been shown to additionally modulate Env ectodomain structure on the cell and virion surface, affect Env reactivity and viral sensitivity to conformation-dependent neutralizing antibodies, and alter cell–cell and virus–cell fusogenicity of Env. This review provides an overview of the Env structure and function with a particular emphasis on the CTT and recent studies that highlight its functionally rich nature. PMID:23079381

Steckbeck, Jonathan D.; Kuhlmann, Anne-Sophie

2013-01-01

175

A Fusion Intermediate gp41 Immunogen Elicits Neutralizing Antibodies to HIV-1.  

PubMed

The membrane-proximal external region (MPER) of the human immunodeficiency virus, type 1 (HIV-1) envelope glycoprotein subunit gp41 is targeted by potent broadly neutralizing antibodies 2F5, 4E10, and 10E8. These antibodies recognize linear epitopes and have been suggested to target the fusion intermediate conformation of gp41 that bridges viral and cellular membranes. Anti-MPER antibodies exert different degrees of membrane interaction, which is considered to be the limiting factor for the generation of such antibodies by immunization. Here we characterize a fusion intermediate conformation of gp41 (gp41int-Cys) and show that it folds into an elongated ?12-nm-long extended structure based on small angle x-ray scattering data. Gp41int-Cys was covalently linked to liposomes via its C-terminal cysteine and used as immunogen. The gp41int-Cys proteoliposomes were administered alone or in prime-boost regimen with trimeric envelope gp140CA018 in guinea pigs and elicited high anti-gp41 IgG titers. The sera interacted with a peptide spanning the MPER region, demonstrated competition with broadly neutralizing antibodies 2F5 and 4E10, and exerted modest lipid binding, indicating the presence of MPER-specific antibodies. Although the neutralization potency generated solely by gp140CA018 was higher than that induced by gp41int-Cys, the majority of animals immunized with gp41int-Cys proteoliposomes induced modest breadth and potency in neutralizing tier 1 pseudoviruses and replication-competent simian/human immunodeficiency viruses in the TZM-bl assay as well as responses against tier 2 HIV-1 in the A3R5 neutralization assay. Our data thus demonstrate that liposomal gp41 MPER formulation can induce neutralization activity, and the strategy serves to improve breadth and potency of such antibodies by improved vaccination protocols. PMID:25160627

Lai, Rachel P J; Hock, Miriam; Radzimanowski, Jens; Tonks, Paul; Hulsik, David Lutje; Effantin, Gregory; Seilly, David J; Dreja, Hanna; Kliche, Alexander; Wagner, Ralf; Barnett, Susan W; Tumba, Nancy; Morris, Lynn; LaBranche, Celia C; Montefiori, David C; Seaman, Michael S; Heeney, Jonathan L; Weissenhorn, Winfried

2014-10-24

176

Lysis of Human Immunodeficiency Virus Type 1 by a Specific Secreted Human Phospholipase A2?  

PubMed Central

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.

2007-01-01

177

Improved cellular and humoral immune responses in vivo following targeting of HIV Gag to dendritic cells within human anti-human DEC205 monoclonal antibody  

PubMed Central

Protein vaccines for T-cell immunity are not being prioritized because of poor immunogenicity. To overcome this hurdle, proteins are being targeted to maturing dendritic cells (DCs) within monoclonal antibodies (mAbs) to DC receptors. To extend the concept to humans, we immunized human immunoglobulin-expressing mice with human DEC205 (hDEC205) extracellular domain. 3D6 and 3G9 mAbs were selected for high-affinity binding to hDEC205. In addition, CD11c promoter hDEC205 transgenic mice were generated, and 3G9 was selectively targeted to DCs in these animals. When mAb heavy chain was engineered to express HIV Gag p24, the fusion mAb induced interferon-?– and interleukin-2–producing CD4+ T cells in hDEC205 transgenic mice, if polynocinic polycytidylic acid was coadministered as an adjuvant. The T-cell response was broad, recognizing at least 3 Gag peptides, and high titers of anti-human immunoglobulin G antibody were made. Anti-hDEC205 also improved the cross-presentation of Gag to primed CD8+ T cells from HIV-infected individuals. In all tests, 3D6 and 3G9 targeting greatly enhanced immunization relative to nonbinding control mAb. These results provide preclinical evidence that in vivo hDEC205 targeting increases the efficiency with which proteins elicit specific immunity, setting the stage for proof-of-concept studies of these new protein vaccines in human subjects. PMID:20668230

Cheong, Cheolho; Choi, Jae-Hoon; Vitale, Laura; He, Li-Zhen; Trumpfheller, Christine; Bozzacco, Leonia; Do, Yoonkyung; Nchinda, Godwin; Park, Sung Ho; Dandamudi, Durga Bhavani; Shrestha, Elina; Pack, Maggi; Lee, Han-Woong; Keler, Tibor

2010-01-01

178

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

179

Inborn errors of metabolism underlying primary immunodeficiencies.  

PubMed

A number of inborn errors of metabolism (IEM) have been shown to result in predominantly immunologic phenotypes, manifesting in part as inborn errors of immunity. These phenotypes are mostly caused by defects that affect the (i) quality or quantity of essential structural building blocks (e.g., nucleic acids, and amino acids), (ii) cellular energy economy (e.g., glucose metabolism), (iii) post-translational protein modification (e.g., glycosylation) or (iv) mitochondrial function. Presenting as multisystemic defects, they also affect innate or adaptive immunity, or both, and display various types of immune dysregulation. Specific and potentially curative therapies are available for some of these diseases, whereas targeted treatments capable of inducing clinical remission are available for others. We will herein review the pathogenesis, diagnosis, and treatment of primary immunodeficiencies (PIDs) due to underlying metabolic disorders. PMID:25081841

Parvaneh, Nima; Quartier, Pierre; Rostami, Parastoo; Casanova, Jean-Laurent; de Lonlay, Pascale

2014-10-01

180

Mucosal Transmission of Human Immunodeficiency Virus  

PubMed Central

Since the beginning of the AIDS pandemic, and following the discovery of the human immunodeficiency virus (HIV) as the etiological agent of the disease, it was clear that the virus gains access to the human host predominantly through the mucosal tissue after sexual exposure. As a consequence, the female genital tract (vaginal and cervical), as well as the rectal, penile, and oral mucosae have been extensively studied over the last thirty years towards a better understanding of - and to develop strategies to prevent - sexual HIV transmission. This review seeks to describe the biology of the events leading to HIV infection through the human mucosa and introduce some of the approaches attempted to prevent the sexual transmission of HIV. PMID:22264040

Tebit, Denis M.; Ndembi, Nicaise; Weinberg, Aaron; Quinones-Mateu, Miguel E.

2013-01-01

181

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

182

Human immunodeficiency virus and leprosy: an update.  

PubMed

Coinfection with human immunodeficiency virus (HIV) has a major effect on the natural history of many infectious diseases, particularly mycobacterial diseases. Early in the HIV epidemic, it was predicted that HIV infection would worsen leprosy outcomes, with more patients developing lepromatous disease, an impaired response to multidrug therapy and fewer reactions. However, studies on the epidemiologic and clinical aspects of leprosy suggest that the course of leprosy in coinfected patients has not been greatly altered by HIV. In contrast, initiation of antiretroviral treatment has been reported to be associated with activation of subclinical Mycobacterium leprae infection and exacerbation of existing leprosy lesions. With regular new discoveries about the interaction of leprosy and HIV, the need to maintain research in this field is of considerable importance. PMID:21095536

Lockwood, Diana N J; Lambert, Saba M

2011-01-01

183

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

184

Cross-protective immune responses induced in rhesus macaques by immunization with attenuated macrophage-tropic simian immunodeficiency virus.  

PubMed Central

The simian immunodeficiency virus (SIV) macaque model of AIDS has provided a valuable system with which to investigate vaccine approaches for protection against human immunodeficiency virus type 1 (HIV-1) infection. In particular, the ability of macaques persistently infected with attenuated infectious molecular clones of SIV to resist challenge with the pathogenic parental swarm has conclusively demonstrated that protective immunity can be achieved by immunization prior to exposure. The breadth of these protective responses and the immunological correlates of protection, however, have not been identified. In addition, vaccine studies have mainly employed lymphocyte-tropic strains of HIV-1 and SIV. Recent studies have implicated macrophage-tropic strains in the transmission of HIV-1 and have suggested that these virus strains should be examined in vaccine strategies. Macrophage-tropic viruses may confer additional advantages in the induction of protective immunity by replication in antigen-presenting cells. In this study, the immune response of rhesus macaques inoculated with an attenuated macrophage-tropic recombinant of SIVmac239 (SIV/17E-Cl) was evaluated with respect to protective immunity by heterologous challenge at various times after infection. Vigorous type-specific neutralizing-antibody responses restricted to SIV/17E-Cl were evident by 2 weeks postinfection. By 7 months, however, cross-reactive neutralizing antibodies emerged which neutralized not only SIV/17E-Cl but also the heterologous primary isolate SIV/DeltaB670. Challenge of SIV/17E-Cl-infected monkeys with SIV/DeltaB670 at various times postinfection demonstrated that protective responses were associated with the appearance of cross-reactive neutralizing antibodies. Furthermore, passive transfer of sera from SIV/17E-Cl-infected animals passively protected two of four naive recipients. PMID:7707496

Clements, J E; Montelaro, R C; Zink, M C; Amedee, A M; Miller, S; Trichel, A M; Jagerski, B; Hauer, D; Martin, L N; Bohm, R P

1995-01-01

185

Four nightmares for net neutrality  

Microsoft Academic Search

What is the economic substance behind net neutrality, the populist policy debate du jour? The authors assesses the basic economics behind net neutrality. To be sure, this debate has many arcane facets. For example, a couple years ago the FCC legally exempted US broadband firms - cable modem and DSL providers - from what are known as \\

Shane Greenstein

2006-01-01

186

Net neutrality and investment incentives  

Microsoft Academic Search

This article analyzes the effects of net neutrality regulation on investment incentives for Internet service providers (ISPs) and content providers (CPs), and their implications for social welfare. Concerning the ISPs' investment incentives, we find that capacity expansion decreases the sale price of the priority right under the discriminatory regime. Thus, contrary to ISPs' claims that net neutrality regulations would have

Jay Pil Choi; Byung-Cheol Kim

2010-01-01

187

The delusions of net neutrality  

Microsoft Academic Search

Service providers argue that if net neutrality is not enforced, they will have sufficient incentives to build special high-quality channels that will take the Internet to the next level of its evolution. But what if they do get their wish, net neutrality is consigned to the dustbin, and they do build their new services, but nobody uses them? If the

Andrew Odlyzko

2008-01-01

188

Casimir Force - Neutral or Electrostatic?  

Microsoft Academic Search

Since Casimir, the attractive force between neutral metal surfaces separated by an evacuated gap has been attributed to the zero point energy (ZPE) of quantum mechanics. But the Casimir theory has difficulty in explaining how contact of neutral surfaces in micro electro-mechanical systems (MEMS) devices can cause permanent adhesion without the discharge of the build-up of static charge. A modified

T. V. Prevenslik

189

Human immunodeficiency virus encephalitis in SCID mice.  

PubMed Central

The human immunodeficiency virus (HIV) is neuroinvasive and commonly causes cognitive and motor deficits during the later stages of viral infection. (referred to as HIV dementia). The mechanism(s) for disease revolves around secretory products produced from immune-activated brain macrophages/microglia. Recently, we developed an animal model system for HIV dementia that contains xenografts of HIV-1-infected cells inoculated into brains of mice with severe combined immunodeficiency (SCID). This animal system was used to quantitatively evaluate HIV-induced neuropathology. Xenografts of HIV-1-infected human monocytes (placed into the putamen and cortex of SCID mice) remained viable for 5 weeks. HIV-1 p24 antigen expression in mouse brain was persistent. Progressive inflammatory responses (including astrogliosis and cytokine production), which began at 3 days, peaked at day 12. The range of astrocyte proliferative reactions exceeded the inoculation site by > 1000 microns. Brains with virus-infected monocytes showed a > or = 1.6-fold increase in glial fibrillary acidic protein (staining distribution and intensity) as compared with similarly inoculated brains with uninfected control monocytes. These findings paralleled the accumulation and activation of murine microglia (increased branching of cell processes, formation of microglial nodules, interleukin (IL)-1 beta and IL-6 expression). An inflammatory reaction of human monocytes (as defined by HLA-DR, IL-1 beta, IL-6, and tumor necrosis factor-alpha expression) and neuronal injury (apoptosis) also developed after virus-infected monocyte xenograft placement into mouse brain tissue. These data, taken together, demonstrate that this SCID mouse model of HIV-1 neuropathogenesis can reproduce key aspects of disease (virus-infected macrophages, astrocytosis, microglial activation, and neuronal damage). This model may serve as an important means for therapeutic development directed toward improving mental function in HIV-infected subjects with cognitive and motor dysfunction. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 14 Figure 15 PMID:8780406

Persidsky, Y.; Limoges, J.; McComb, R.; Bock, P.; Baldwin, T.; Tyor, W.; Patil, A.; Nottet, H. S.; Epstein, L.; Gelbard, H.; Flanagan, E.; Reinhard, J.; Pirruccello, S. J.; Gendelman, H. E.

1996-01-01

190

Is science metaphysically neutral?  

PubMed

This paper challenges the claim that science is metaphysically neutral upheld by contenders of the separation of peacefully co-existent science and religion and by evolutionary theists. True, naturalistic metaphysical claims can neither be refuted nor proved and are thus distinct from empirical hypotheses. However, metaphysical assumptions not only regulate the theoretical and empirical study of nature, but are increasingly supported by the growing empirical body of science. This historically evolving interaction has contributed to the development of a naturalistic worldview that renounces the necessity of a transcendent god and of purposeful design. The thesis presented here differs not only from the claims of the "separatists" and of evolutionary theists. In pointing to the metaphysical aspects of science, I also criticize the failure of some evolutionary naturalists to distinguish between empirical and metaphysical contentions. Most important, based on the examination of science suggested here, creationists' false accusation that science is only a naturalistic dogma is refuted. Finally, the difficulties involved in the position endorsed here for the public support of evolution are acknowledged, taking into account the high religious profile of the American society and the social and political context in the US and in other countries. PMID:22771725

Fry, Iris

2012-09-01

191

Immunodeficiency and autoimmunity: lessons from systemic lupus erythematosus  

PubMed Central

Recent evidence suggests that systemic autoimmunity and immunodeficiency are not separate entities, but rather interconnected processes. Immunodeficiency results from distinct defects of the immune response and primarily presents as infections, but also frequently with autoimmune features. Systemic autoimmunity is the combined effect of multiple genetic variations, infectious and immunoregulatory factors that result in dominant autoimmune manifestations in addition to frequent and opportunistic infections. The overlap in disease manifestations and symptoms suggests that immunodeficiency should be considered in the presence of autoimmunity, and vice versa. In this review, we present the shared or similar aspects of immunodeficiency and autoimmunity using systemic lupus erythematosus as a paradigm and discuss the implications for clinical care. PMID:22177735

Grammatikos, Alexandros P.; Tsokos, George C.

2011-01-01

192

Peritoneal coccidioidomycosis associated with human immunodeficiency virus infection.  

PubMed

Peritoneal coccidioidomycosis is extremely rare. This report describes a patient infected with the human immunodeficiency virus who presented with unexplained ascites and was found to have peritoneal coccidioidomycosis. The ascites had a low serum-ascites albumin gradient, and laparoscopy showed peritoneal implants that grew Coccidioides immitis. This case is unique in several ways; this is the first case in which a patient's acquired immunodeficiency syndrome-defining illness was peritoneal coccidioidomycosis, and the serum-ascites albumin gradient determination as well as laparoscopy provided information critical to the diagnosis. This patient's dramatic response to systemic antifungal therapy, as evidenced by resolution of ascites and constitutional symptoms, underscores the importance of timely diagnosis and prompt therapy. In summary, this report reviews the previous cases of coccidioidal peritonitis and reports the first case in which localized peritoneal coccidioidomycosis was the acquired immunodeficiency syndrome-defining illness in a human immunodeficiency virus-infected patient. PMID:1531643

Jamidar, P A; Campbell, D R; Fishback, J L; Klotz, S A

1992-03-01

193

Adenocarcinoma of the stomach with common variable immunodeficiency syndrome.  

PubMed

Two patients had adenocarcinoma of the stomach in association with common variable immunodeficiency syndrome. There has been an increased prevalence of malignancy in this late-onset immunodeficient state. Similar to five previously reported cases, our patients had gastric carcinoma as a late complication. Further documentation of this association stresses the need for long-term follow-up in this premalignant condition. PMID:718318

Battle, W M; Brooks, F P

1978-11-01

194

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

195

Association of common variable immunodeficiency with vitamin B6 deficiency  

Microsoft Academic Search

Objective:To study the prevalence of vitamin B6 deficiency in common variable immunodeficiency and the impact of vitamin B6 supplementation on immune function in the disorder.Design:Open, non-blinded.Setting:Medical School Hannover, Hannover, Germany.Subjects:Plasma vitamin B6 concentrations were measured in all the 54 common variable immunodeficiency (CVID) patients visiting our outpatients' clinics in 2005.Interventions:The 17 patients with a decreased vitamin B6 concentration were recommended

J Bierwirth; K U Ulbricht; R E Schmidt; T Witte

2008-01-01

196

Non-Hodgkin lymphoma in common variable immunodeficiency.  

PubMed

The association between cancer and immunodeficiency is well established. In common variable immunodeficiency (CVI), a primary immunodeficiency disease characterized by low serum immunoglobulins and poor antibody production, we previously reported a total of 13 cancers in 11 individuals arising in continuously observed group of patients. Of the 13, 7 were NHL and 1 was a myeloma which progressed to lymphoma. We report here the histologic, immunologic, cytogenetic, and clinical features of these 8 NHL along with 3 new lymphomas which have appeared in this group (now 117 patients). From our studies, the lymphomas which have arisen in CVI share certain features with the lymphomas which appear in the childhood immunodeficient syndromes. Wiskott Aldrich Syndrome, Ataxia Telangiectasia, or severe combined immunodeficiency: they are similar in overall frequency (13%), are often B-cell in origin, and extranodal in location. However, unlike the lymphomas of the immunodeficient child, lymphomas in CVI may be more differentiated and secrete immunoglobulin. For CVI patients with stage I or II disease, as for non-Hodgkin lymphomas in general, the prognosis is good. In our group, NHL in CVI have appeared most often in females of the 5th to 7th decade and not in childhood. Cytogenetic studies in lymphomas show that cytogenic abnormalities, including chromosomal translocation, can be found in this group, but more studies will be needed to assess the frequency of these events. PMID:1829873

Cunningham-Rundles, C; Lieberman, P; Hellman, G; Chaganti, R S

1991-06-01

197

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

198

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

199

Combined intra- and extracellular immunization against human immunodeficiency virus type 1 infection with a human anti-gp120 antibody.  

PubMed Central

In this study, a human CD4+ T lymphocyte line was transduced to secrete Fab fragments of a broadly neutralizing human monoclonal antibody F105 that reacts with the CD4-binding site of human immunodeficiency virus type 1 (HIV-1) envelope protein. In the transduced cells infected with HIV-1, the nascent Fab fragments bind intracellularly to the HIV-1 envelope protein and inhibit HIV-1 production. The secreted Fab fragments are able to neutralize cell-free HIV-1. In addition, the nascent Fab fragments can inhibit HIV-1 production by binding intracellularly to envelope mutants that escape neutralization by extracellular F105 antibody. The combined intra- and extracellular binding activities of the expressed Fab fragments result in the efficient blocking of cytopathic syncytium formation and infectious virus production. Thus, these antibody-producing T lymphocytes are not only resistant to HIV-1 infection but also can protect surrounding lymphocytes by secreting neutralizing antibodies. This novel strategy of combining intracellular and extracellular immunization may be useful for gene therapy of AIDS and other diseases. Images PMID:8016092

Chen, S Y; Khouri, Y; Bagley, J; Marasco, W A

1994-01-01

200

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

201

Trustworthiness as a Limitation on Network Neutrality  

E-print Network

............................................................................ D. Trustworthiness and Wireless Net Neutrality.................. IV. KEEPING TRUSTWORTHINESS591 Trustworthiness as a Limitation on Network Neutrality Aaron J. Burstein* Fred B. Schneider** I TRUSTWORTHINESS THROUGH THE NETWORK NEUTRALITY DEBATE

Schneider, Fred B.

202

Cryo-Electron Tomographic Structure of an Immunodeficiency Virus Envelope Complex In Situ  

PubMed Central

The envelope glycoprotein (Env) complexes of the human and simian immunodeficiency viruses (HIV and SIV, respectively) mediate viral entry and are a target for neutralizing antibodies. The receptor binding surfaces of Env are in large part sterically occluded or conformationally masked prior to receptor binding. Knowledge of the unliganded, trimeric Env structure is key for an understanding of viral entry and immune escape, and for the design of vaccines to elicit neutralizing antibodies. We have used cryo-electron tomography and averaging to obtain the structure of the SIV Env complex prior to fusion. Our result reveals novel details of Env organisation, including tight interaction between monomers in the gp41 trimer, associated with a three-lobed, membrane-distal gp120 trimer. A cavity exists at the gp41–gp120 trimer interface. Our model for the spike structure agrees with previously predicted interactions between gp41 monomers, and furthers our understanding of gp120 interactions within an intact spike. PMID:16933990

Zanetti, Giulia; Briggs, John A. G; Grunewald, Kay; Sattentau, Quentin J; Fuller, Stephen D

2006-01-01

203

Gp120-induced Bob/GPR15 activation: a possible cause of human immunodeficiency virus enteropathy.  

PubMed

Human immunodeficiency virus (HIV)-infected patients often develop malabsorption and increased intestinal permeability with diarrhea, called HIV enteropathy, even without enteric opportunistic infections. HIV gp120-induced calcium signaling, microtubule loss, and physiological changes resembling HIV enteropathy were previously found in the HT-29 intestinal cell line. How gp120 caused these changes was unclear. We show that the HIV co-receptor Bob/GPR15, unlike CCR5 and CXCR4, is abundant at the basal surface of small intestinal epithelium. The gp120-induced effects on HT-29 cells were inhibited by anti-Bob neutralizing antibodies, the selective G protein inhibitor pertussis toxin, and the phospholipase inhibitor U73122, but not neutralizing antibodies to CXCR4. Gp120 strains that induced signaling in HT-29 cells also induced calcium fluxes in Bob-transfected Ghost (3) cells, whereas gp120 strains not activating HT-29 cells also did not activate Bob-transfected cells. Bob is the first HIV co-receptor shown to be abundantly expressed on the basolateral surface of intestinal epithelium. Although Bob is an inefficient infection-inducing co-receptor, it mediates viral strain-specific gp120-induced calcium signaling at low, physiologically reasonable gp120 concentrations, up to 10,000-fold lower gp120 concentrations than the principal co-receptors. Gp120-induced Bob activation is a plausible cause of HIV enteropathy. PMID:11696454

Clayton, F; Kotler, D P; Kuwada, S K; Morgan, T; Stepan, C; Kuang, J; Le, J; Fantini, J

2001-11-01

204

Development of a sensitive quantitative focal assay for human immunodeficiency virus infectivity.  

PubMed Central

Accurate and sensitive quantitation of infectious human immunodeficiency virus (HIV) has been difficult to achieve. In this report, a quantitative focal immunoassay (FIA) for HIV was developed using human HeLa cells rendered susceptible to HIV infection by introduction of the CD4 gene via a retrovirus vector. Infected cells were identified by using human anti-HIV antibodies or mouse monoclonal antibodies specific for HIV together with secondary fluorescein- or peroxidase-conjugated antibody specific for mouse or human immunoglobulins. The assay identified cells infected with either wild-type or culture-adapted HIV isolates and was capable of detecting 1 positive cell in 10(6) cells. The FIA was also effective at detecting cell-free HIV, and in contrast to assays using A3.01, CEM, and other human leukemia cells, the FIA detected most wild-type HIV isolates. HIV neutralization could be determined by using the FIA, and two monoclonal antibodies reactive with HIV gp120 were found to neutralize only the LAV-IIIB strain of HIV. These monoclonal antibodies, as well as antibodies in serum samples from patients with acquired immune deficiency syndrome, were able to inhibit the spread of HIV infection in human lymphocyte suspension cultures but not in CD4-positive HeLa cells growing attached to plastic dishes. Images PMID:3047430

Chesebro, B; Wehrly, K

1988-01-01

205

Role of a Putative gp41 Dimerization Domain in Human Immunodeficiency Virus Type 1 Membrane Fusion  

SciTech Connect

The entry of human immunodeficiency virus type 1 (HIV-1) into a target cell entails a series of conformational changes in the gp41 transmembrane glycoprotein that mediates the fusion of the viral and target cell membranes. A trimer-of-hairpins structure formed by the association of two heptad repeat (HR) regions of the gp41 ectodomain has been implicated in a late step of the fusion pathway. Earlier native and intermediate states of the protein are postulated to mediate the antiviral activity of the fusion inhibitor enfuvirtide and of broadly neutralizing monoclonal antibodies (NAbs), but the details of these structures remain unknown. Here, we report the identification and crystal structure of a dimerization domain in the C-terminal ectodomain of gp41 (residues 630 to 683, or C54). Two C54 monomers associate to form an asymmetric, antiparallel coiled coil with two distinct C-terminal {alpha}-helical overhangs. This dimer structure is conferred largely by interactions within a central core that corresponds to the sequence of enfuvirtide. The mutagenic alteration of the dimer interface severely impairs the infectivity of Env-pseudotyped viruses. Moreover, the C54 structure binds tightly to both the 2F5 and 4E10 NAbs and likely represents a potential intermediate conformation of gp41. These results should enhance our understanding of the molecular basis of the gp41 fusogenic structural transitions and thereby guide rational, structure-based efforts to design new fusion inhibitors and vaccine candidates intended to induce broadly neutralizing antibodies.

Liu, J.; Deng, Y; Li, Q; Dey, A; Moore, J; Lu, M

2010-01-01

206

Neutral atom imaging at Mercury  

NASA Astrophysics Data System (ADS)

The feasibility of neutral atom detection and imaging in the Hermean environment is discussed in this study. In particular, we consider those energetic neutral atoms (ENA) whose emission is directly related to solar wind entrance into Mercury's magnetosphere. In fact, this environment is characterised by a weak magnetic field; thus, cusp regions are extremely large if compared to the Earth's ones, and intense proton fluxes are expected there. Our study includes a model of H + distribution in space, energy and pitch angle, simulated by means of a single-particle, Monte-Carlo simulation. Among processes that could generate neutral atom emission, we focus our attention on charge-exchange and ion sputtering, which, in principle, are able to produce directional ENA fluxes. Simulated neutral atom images are investigated in the frame of the neutral particle analyser-ion spectrometer (NPA-IS) SERENA experiment, proposed to fly on board the ESA mission BepiColombo/MPO. The ELENA (emitted low-energy neutral atoms) unit, which is part of this experiment, will be able to detect such fluxes; instrumental details and predicted count rates are given.

Mura, A.; Orsini, S.; Milillo, A.; Di Lellis, A. M.; De Angelis, E.

2006-02-01

207

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

208

Human immunodeficiency virus infection and pregnancy.  

PubMed

Human immunodeficiency virus infection profoundly affects the medical community and is spreading rapidly in women of childbearing age worldwide. Transmission of HIV from mother to child can occur in utero, during labor, or after delivery through breast-feeding. Most of the infants are infected during delivery. We focus on the factors affecting the transmission of HIV, diagnostic and resistance tests, strategies to prevent mother-to-child transmission with special reference to mode of delivery, infant feeding, and use of antiretroviral therapy. The risk of infection for the infant can be decreased by reducing maternal viral load, by elective cesarean delivery, and by avoidance of breast-feeding. The efficacy of antiretroviral treatment should be balanced against the possibility of embryonic or fetal toxicity. The choice of therapy should be based on the woman's treatment history, the clinical status, and the available prognostic markers, which are related to the progression of disease in the mother and the risk of mother-to-child transmission HIV transmission. PMID:17113971

Petropoulou, Haritini; Stratigos, Alexander J; Katsambas, Andreas D

2006-01-01

209

Human immunodeficiency virus-associated nephropathy.  

PubMed

Human immunodeficiency virus-associated nephropathy (HIVAN) is a clinicopathological entity characterised by proteinuria, rapidly developing azotemia and histologically by collapsig variant of focal and segmental glomerulosclerosis with acute tubular necrosis and mild interstitial inflammation. Untreated, it may result in end stage renal disease (ESRD) in as little as four months. The incidence of HIVAN continues to increase and is the single most common cause of chronic renal disease in HIV-1 seropositive patients. It affects predominantly black individuals. Exact pathogenesis is still not clear but a great deal of progress has been made in the recent past by studies on transgenic mouse model, renal cell cultures and from study of human biopsy material. Current considerations revolve around the role of HIV or protein in renal epithelium and the effects of cytokines, including transforming growth factor-beta and basic fibroblast growth factor on renal structures. Different modalities of treatment with corticosteroids, zidovudine or angiotensin converting enzyme inhibitors have been tried with modest success. PMID:11837470

Rajvanshi, P; Gupta, B

2001-08-01

210

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

211

A Conserved Tryptophan-Rich Motif in the Membrane-Proximal Region of the Human Immunodeficiency Virus Type 1 gp41 Ectodomain Is Important for Env-Mediated Fusion and Virus Infectivity  

Microsoft Academic Search

Mutations were introduced into the ectodomain of the human immunodeficiency virus type 1 (HIV-1) transmembrane envelope glycoprotein, gp41, within a region immediately adjacent to the membrane-spanning domain. This region, which is predicted to form an a-helix, contains highly conserved hydrophobic residues and is unusually rich in tryptophan residues. In addition, this domain overlaps the epitope of a neutralizing monoclonal antibody,

KARL SALZWEDEL; JOHN T. WEST; ERIC HUNTER

1999-01-01

212

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

213

Frequent Transmission of Immunodeficiency Viruses among Bobcats and Pumas?  

PubMed Central

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.

2007-01-01

214

Neutral and Non-Neutral Evolution of Drosophila Mitochondrial DNA  

PubMed Central

To test hypotheses of neutral evolution of mitochondrial DNA (mtDNA), nucleotide sequences were determined for 1515 base pairs of the NADH dehydrogenase subunit 5 (ND5) gene in the mitochondrial DNA of 29 lines of Drosophila melanogaster and 9 lines of its sibling species Drosophila simulans. In contrast to the patterns for nuclear genes, where D. melanogaster generally exhibits much less nucleotide polymorphism, the number of segregating sites was slightly higher in a global sample of nine ND5 sequences in D. melanogaster (s = 8) than in the nine lines of D. simulans (s = 6). When compared to variation at nuclear loci, the mtDNA variation in D. melanogaster does not depart from neutral expectations. The ND5 sequences in D. simulans, however, show fewer than half the number of variable sites expected under neutrality when compared to sequences from the period locus. While this reduction in variation is not significant at the 5% level, HKA tests with published restriction data for mtDNA in D. simulans do show a significant reduction of variation suggesting a selective sweep of variation in the mtDNA in this species. Tests of neutral evolution based on the ratios of synonymous and replacement polymorphism and divergence are generally consistent with neutral expectations, although a significant excess of amino acid polymorphism within both species is localized in one region of the protein. The rate of mtDNA evolution has been faster in D. melanogaster than in D. simulans and the population structure of mtDNA is distinct in these species. The data reveal how different rates of mtDNA evolution between species and different histories of neutral and adaptive evolution within species can compromise historical inferences in population and evolutionary biology. PMID:7851771

Rand, D. M.; Dorfsman, M.; Kann, L. M.

1994-01-01

215

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

MedlinePLUS

... Genetic testing 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 ...

216

AIDS (Acquired Immunodeficiency Syndrome): Information on Global Dimensions and Possible Impacts.  

National Technical Information Service (NTIS)

The fact sheet provides information on (1) the impact of the Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS) on world population and demographics and (2) the likely effects of AIDS on Zaire. Because scientists lack importa...

1987-01-01

217

21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.  

...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. 866...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification. The in vitro HIV drug resistance genotype assay...

2014-04-01

218

21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.  

Code of Federal Regulations, 2013 CFR

...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. 866...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification . The in vitro HIV drug resistance genotype assay...

2013-04-01

219

21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.  

Code of Federal Regulations, 2010 CFR

...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. 866...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification . The in vitro HIV drug resistance genotype assay...

2010-04-01

220

21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.  

Code of Federal Regulations, 2012 CFR

...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. 866...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification . The in vitro HIV drug resistance genotype assay...

2012-04-01

221

21 CFR 866.3950 - In vitro human immunodeficiency virus (HIV) drug resistance genotype assay.  

Code of Federal Regulations, 2011 CFR

...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. 866...In vitro human immunodeficiency virus (HIV) drug resistance genotype assay. (a) Identification . The in vitro HIV drug resistance genotype assay...

2011-04-01

222

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

223

Agents for treating human immunodeficiency virus infection.  

PubMed

The replicative cycle of the human immunodeficiency virus (HIV) is reviewed, and currently used and investigational agents directed against the virus are discussed. The first step in the replication of HIV is selective binding of the envelope glycoprotein to CD4 receptors located on T lymphocytes. The virion is then uncoated within the cytoplasm, yielding viral genomic RNA. Reverse transcriptase uses the viral RNA as a template to form single-stranded DNA, which is duplicated to form proviral DNA through the activity of ribonuclease H. Host RNA polymerases transcribe the integrated proviral DNA into messenger RNA, and there is subsequent translation to viral proteins. After translation, further modification of precursor polyproteins is necessary to produce functional peptides. The assembled virus then buds from the cell surface and invades other cells. Targets of drug intervention in the replicative cycle include (1) binding and entry, (2) reverse transcriptase, (3) transcription and translation, and (4) viral maturation and budding. Inhibitors of binding and entry include recombinant soluble CD4, immunoadhesins, peptide T, and hypericin. Nucleoside reverse-transcriptase inhibitors include zidovudine, didanosine, zalcitabine, and stavudine. Foscarnet, tetrahydroimidazobenzo-diazepinthione compounds, and nevirapine are some nonnucleoside reverse-transcriptase inhibitors. Inhibitors of transcription and translation include antagonists of the tat gene and GLQ223. Castanospermine, N-butyldeoxynojirimycin, and protease inhibitors interfere with viral maturation and budding. Drug combinations that have been or are being investigated include zidovudine plus interferon alfa, zidovudine plus zalcitabine, and zidovudine plus didanosine. Four agents currently have approved labeling for use against HIV infection: zidovudine, didanosine, zalcitabine, and stavudine. Monotherapy with zidovudine remains the treatment of first choice. Although progress has been made in developing drug therapies for HIV infection, more selective and more potent drugs are urgently needed. The best approach at present is to optimize the use of available agents, continue to investigate new therapies, and educate the public about prevention. PMID:7801986

Acosta, E P; Fletcher, C V

1994-09-15

224

Specificity of antibodies produced against native or desialylated human immunodeficiency virus type 1 recombinant gp160.  

PubMed Central

In a previous report we have shown that, in contrast to antibodies produced against native or fully deglycosylated human immunodeficiency virus type 1 (HIV-1) gp160 in rabbits, antibodies raised against desialylated HIV-1 gp160 also recognize gp140 from HIV-2 at high titers. Here, we characterize the fine specificity of these cross-reactive antibodies. Inhibition assays with a panel of synthetic peptides as competitors showed that cross-reactivity to gp140 was due to antibodies that were specific for the region encompassing HIV-1 gp41 immunodominant epitope, mimicked by peptide P39 (residues 583 to 609), the latter being able to totally inhibit the formation of complexes between radiolabeled HIV-2 gp140 and antibodies elicited by desialylated HIV-1 gp160. In addition, anti-desialylated gp160 antibodies retained on a P39 affinity column still bound HIV-2 gp140. Fine mapping has enabled us to localize the cross-reactive epitope within the N-terminal extremity of the gp41 immunodominant region. Interestingly, this cross-reactive antibody population did not recognize glycosylated or totally deglycosylated simian immunodeficiency virus gp140 despite an amino acid homology with HIV-1 within this region that is comparable to that of HIV-2. This cross-reactivity between HIV-1 and HIV-2 did not correlate with cross-neutralization. These results illustrate the influence of carbohydrate moieties on the specificity of the antibodies produced and clearly indicate that such procedures may be an efficient way to raise specific immune responses that are not type specific. Moreover, this cross-reactivity might explain the double-positive reactivity observed, in some human sera, against both HIV-1 and HIV-2 envelope antigens. PMID:7679751

Benjouad, A; Gluckman, J C; Montagnier, L; Bahraoui, E

1993-01-01

225

In vivo Targeting of Human Neutralizing Antibodies against CD55 and CD59 to Lymphoma Cells Increases the Antitumor Activity of Rituximab  

Microsoft Academic Search

An in vivo model of human CD20+ B-lymphoma was established in severe combined immunodeficiency mice to test the ability of human neutralizing miniantibodies to CD55 and CD59(MB55 and MB59) to enhance the therapeutic effect of rituximab. The miniantibodies contained single-chain fragment variables and the hinge-CH2-CH3 domains of human IgG1. LCL2 cells were selected for the in vivo study among six

Paolo Macor; Claudio Tripodo; Sonia Zorzet; Erich Piovan; Fleur Bossi; Roberto Marzari; Alberto Amadori

226

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

227

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

228

Neurosyphilis in a man with human immunodeficiency virus.  

PubMed

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; Khachemoune, Amor

2014-08-01

229

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

230

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

231

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

232

Human Immunodeficiency Virus gag and protease: partners in resistance  

E-print Network

-terminal autoprocessing of HIV-1 protease. Nature 2008, 455:693–696. 18. Craig JC, Duncan IB, Hockley D, Grief C, Roberts NA, Mills JS: Antiviral properties of Ro 31-8959, an inhibitor of human immunodeficiency virus (HIV) proteinase. Antiviral Res 1991, 16:295–305. 19... resistant mutant precursors of HIV-1 protease by clinical inhibitors. Proc Natl Acad Sci U S A 2011, 108:9072–9077. 29. Davis DA, Soule EE, Davidoff KS, Daniels SI, Naiman NE, Yarchoan R: Activity of Human Immunodeficiency Virus Type 1 Protease Inhibitors...

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

2012-08-06

233

Poor specific antibody response immunodeficiency (dysgammaglobulinemia) predates systemic lupus erythematosus.  

PubMed

Poor specific antibody response is a well-known primary immunodeficiency that is related to hypogammaglobulinemia or common variable immunodeficiency (CVID). The co-existence of CVID or hypogammaglobulinemia and systemic lupus erythematosus (SLE) has been rarely described. In all reported cases, the diagnosis of SLE antedates CVID. We report a 15-year-old Saudi girl who was diagnosed with poor specific antibody response at age 6 years in the form of poor or no antibody response and dysgammaglobulinemia. She developed SLE with musculoskeletal and hematological manifestations, positive antinuclear antibody and high anti-dsDNA nine years later. She was treated with rituximab with good response. PMID:23894048

Al Hamzi, H; Al Shaikh, A; Arnaout, R K

2013-08-01

234

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

235

Market Share Game with adversarial Access providers : A Neutral and a Non-neutral Network  

E-print Network

. We analyze the effects of net neutrality on the charged price and offered QoS as behaviours of APsMarket Share Game with adversarial Access providers : A Neutral and a Non-neutral Network Analysis in the network-neutrality research. In this paper, we study the implication of non-neutrality on the competition

Paris-Sud XI, Université de

236

Immunogenicity of recombinant human immunodeficiency virus type 1-like particles expressing gp41 derivatives in a pre-fusion state  

PubMed Central

The conserved membrane proximal external region (MPER) of the ectodomain of human immunodeficiency virus type 1 (HIV-1) gp41 is the target of two broadly neutralizing antibodies, 2F5 and 4E10. However, no neutralizing antibodies have been elicited against immunogens bearing these epitopes. Given that structural and biochemical studies suggest that the lipid membrane of the virion is involved in their proper configuration, HIV-1 gp41 derivatives in a pre-fusion state were expressed on the surface of immature virus like particles (VLP) derived from Sf9 cells. Guinea pigs were immunized with three doses of VLPs or Sf9 cells presenting gp41 derivatives with or without E. coli heat-labile enterotoxin (LT) as an adjuvant. While immune sera contained high titer anti-VLP antibodies, the specific anti-gp41 antibody responses were low with no neutralizing antibodies detected. An explanation for this absence may be the low level of gp41 expression relative to the many other proteins derived from host cells which are incorporated onto the VLP surface. In addition, the anti-gp41 immune response was preferentially directed to the C-helical domain, away from the MPER. Future vaccine design needs to contend with the complexity of epitope display as well as immunodominance. PMID:17055621

Kim, Mikyung; Qiao, Zhisong; Yu, Jessica; Montefiori, David; Reinherz, Ellis L.

2009-01-01

237

MSFC Skylab neutral buoyancy simulator  

NASA Technical Reports Server (NTRS)

The use of a neutral buoyancy simulator for developing extravehicular activity systems and for training astronauts in weightless activities is discussed. The construction of the facility and the operations are described. The types of tests and the training activities conducted in the simulator are reported. Photographs of the components of the simulator and actual training exercises are included.

1974-01-01

238

Net neutrality: A user's guide  

Microsoft Academic Search

Net neutrality is a complex issue that has generated intense levels of political discussion in the United States, but which has yet to attract significant attention from regulators in the UK. Nevertheless, the question of whether network operators should be prevented from blocking or prioritising certain network traffic or traffic from particular sources is a significant one for a wide range

Paul Ganley; Ben Allgrove

2006-01-01

239

The Economics of Net Neutrality  

Microsoft Academic Search

Robert Hahn and Scott Wallsten argue that mandating net neutrality, like most other forms of price regulation, is poor policy; instead, the government should focus on creating competition in the broadband market by liberalizing more spectrum and reducing entry barriers created by certain local regulations.

Robert W. Hahn; Scott Wallsten

2006-01-01

240

Net Neutrality... Seriously this Time  

Microsoft Academic Search

The net neutrality debate began a few years ago, prematurely, with overheated rhetoric about potential disasters for the Internet but little in the way of real threats requiring immediate government action. Beginning around May 2007, one of the largest ISPs in the US, Comcast, began a program of discriminatory blocking of certain Internet communications protocols. The blocking has focused on

Daniel J. Weitzner

2008-01-01

241

Net Neutrality Paradox: Regulator's Dilemma  

Microsoft Academic Search

Internet has emerged as a disruptive force for the conventional communication model. Internet evolution as the most effective communication medium paved the way for convergent communication services and new business models. The growing incidents of internet service discrimination (1) and service Blockade (2) has once again revived the debate of resolving the old issue of Network neutrality (3). The recent

Khalid Rafique; Chunhui Yuan; Muhammad Saeed

2011-01-01

242

Bachelorscriptie De Verenigde Neutrale Theorie  

E-print Network

, bedacht door Stephen P. Hubbell. Het is bedoeld om de rijkdom aan soorten (diversiteit) en de re- latieve abundantie1 van soorten in ecologische gemeenschappen in ruimte en tijd te verklaren. Hierbij heeft Hubbell totstandkoming van Hubbells neutrale theorie uit te leggen. Deze theorie is het resultaat van de speurtocht naar

Planqué, Bob

243

Bioelectric neutralization of acid waters  

Microsoft Academic Search

An apparatus is to be used in a process for bioelectric neutralization of a body of water having a bottom of anaerobic mud and an acid supernatant liquid. The apparatus comprises a buoy riding on the surface of the water, and upper electrode preferably of carbon suspended from the buoy in the acid supernatant liquid, a lower electrode preferably of

F. D. Sisler; F. E. Senftle

1978-01-01

244

Humean agent-neutral reasons?  

Microsoft Academic Search

In his recent book Slaves of the Passions, Mark Schroeder defends a Humean account of practical reasons (hypotheticalism). He argues that it is compatible with ‘genuinely agent-neutral reasons’. These are reasons that any agent whatsoever has. According to Schroeder, they may well include moral reasons. Furthermore, he proposes a novel account of a reason's weight, which is supposed to vindicate

Daan Evers

2009-01-01

245

Derivation and Characterization of a Simian Immunodeficiency Virus SIVmac239 Variant with Tropism for CXCR4?  

PubMed Central

Like human immunodeficiency virus type 1 (HIV-1), most simian immunodeficiency virus (SIV) strains use CCR5 to establish infection. However, while HIV-1 can acquire the ability to use CXCR4, SIVs that utilize CXCR4 have rarely been reported. To explore possible barriers against SIV coreceptor switching, we derived an R5X4 variant, termed 239-ST1, from the R5 clone SIVmac239 by serially passaging virus in CD4+ CXCR4+ CCR5? SupT1 cells. A 239-ST1 env clone, designated 239-ST1.2-32, used CXCR4 and CCR5 in cell-cell fusion and reporter virus infection assays and conferred the ability for rapid, cytopathic infection of SupT1 cells to SIVmac239. Viral replication was inhibitable by the CXCR4-specific antagonist AMD3100, and replication was abrogated in a novel CXCR4? SupT1 line. Surprisingly, parental SIVmac239 exhibited low-level replication in SupT1 cells that was not observed in CXCR4? SupT1 cells. Only two mutations in the 239-ST1.2-32 Env, K47E in the C1 domain and L328W in the V3 loop, were required for CXCR4 use in cell-cell fusion assays, although two other V3 changes, N316K and I324M, improved CXCR4 use in infection assays. An Env cytoplasmic tail truncation, acquired during propagation of 239-ST1 in SupT1 cells, was not required. Compared with SIVmac239, 239-ST1.2-32 was more sensitive to neutralization by five of seven serum and plasma samples from SIVmac239-infected rhesus macaques and was approximately 50-fold more sensitive to soluble CD4. Thus, SIVmac239 can acquire the ability to use CXCR4 with high efficiency, but the changes required for this phenotype may be distinct from those for HIV-1 CXCR4 use. This finding, along with the increased neutralization sensitivity of this CXCR4-using SIV, suggests a mechanism that could select strongly against this phenotype in vivo. PMID:19605489

Del Prete, Gregory Q.; Haggarty, Beth; Leslie, George J.; Jordan, Andrea P. O.; Romano, Josephine; Wang, Nathaniel; Wang, Jianbin; Holmes, Michael C.; Montefiori, David C.; Hoxie, James A.

2009-01-01

246

Magnitude and Breadth of the Neutralizing Antibody Response in the RV144 and Vax003 HIV-1 Vaccine Efficacy Trials  

PubMed Central

Background.?A recombinant canarypox vector expressing human immunodeficiency virus type 1 (HIV-1) Gag, Pro, and membrane-linked gp120 (vCP1521), combined with a bivalent gp120 protein boost (AIDSVAX B/E), provided modest protection against HIV-1 infection in a community-based population in Thailand (RV144 trial). No protection was observed in Thai injection drug users who received AIDSVAX B/E alone (Vax003 trial). We compared the neutralizing antibody response in these 2 trials. Methods.?Neutralization was assessed with tier 1 and tier 2 strains of virus in TZM-bl and A3R5 cells. Results.?Neutralization of several tier 1 viruses was detected in both RV144 and Vax003. Peak titers were higher in Vax003 and waned rapidly in both trials. The response in RV144 was targeted in part to V3 of gp120.vCP1521 priming plus 2 boosts with gp120 protein was superior to 2 gp120 protein inoculations alone, confirming a priming effect for vCP1521. Sporadic weak neutralization of tier 2 viruses was detected only in Vax003 and A3R5 cells. Conclusion.?The results suggest either that weak neutralizing antibody responses can be partially protective against HIV-1 in low-risk heterosexual populations or that the modest efficacy seen in RV144 was mediated by other immune responses, either alone or in combination with neutralizing antibodies. PMID:22634875

Montefiori, David C.; Karnasuta, Chitraporn; Huang, Ying; Ahmed, Hasan; Gilbert, Peter; de Souza, Mark S.; McLinden, Robert; Tovanabutra, Sodsai; Laurence-Chenine, Agnes; Sanders-Buell, Eric; Moody, M. Anthony; Bonsignori, Mattia; Ochsenbauer, Christina; Kappes, John; Tang, Haili; Greene, Kelli; Gao, Hongmei; LaBranche, Celia C.; Andrews, Charla; Polonis, Victoria R.; Rerks-Ngarm, Supachai; Pitisuttithum, Punnee; Nitayaphan, Sorachai; Kaewkungwal, Jaranit; Self, Steve G.; Berman, Phillip W.; Francis, Donald; Sinangil, Faruk; Lee, Carter; Tartaglia, Jim; Robb, Merlin L.; Haynes, Barton F.; Michael, Nelson L.; Kim, Jerome H.

2012-01-01

247

Major histocompatibility complex class I-associated vaccine protection from simian immunodeficiency virus-infected peripheral blood cells  

PubMed Central

To evaluate the effectiveness of vaccine protection from infected cells from another individual of the same species, vaccinated rhesus macaques (Macaca mulatta) were challenged with peripheral blood mononuclear cells from another animal diagnosed with acquired immune deficiency syndrome (AIDS). Half of the simian immunodeficiency virus (SIV)- vaccinated animals challenged were protected, whereas unprotected vaccinates progressed as rapidly to AIDS. Protection was unrelated to either total antibody titers to human cells, used in the production of the vaccine, to HLA antibodies or to virus neutralizing activity. However, analysis of the serotype of each animal revealed that all animals protected against cell-associated virus challenge were those which were SIV vaccinated and which shared a particular major histocompatibility complex (MHC) class I allele (Mamu-A26) with the donor of the infected cells. Cytotoxic T lymphocytes (CTL) specific for SIV envelope protein were detected in three of four protected animals vs. one of four unprotected animals, suggesting a possible role of MHC class I-restricted CTL in protection from infected blood cells. These findings have possible implications for the design of vaccines for intracellular pathogens such as human immunodeficiency virus (HIV). PMID:8046353

1994-01-01

248

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

249

Gene-based vaccination with a mismatched envelope protects against simian immunodeficiency virus infection in nonhuman primates.  

PubMed

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; Nabel, Gary J

2012-08-01

250

Immunodeficiency syndromes. X-linked agammaglobulinemia, common variable immunodeficiency, Chédiak-Higashi syndrome, Wiskott-Aldrich syndrome, and X-linked lymphoproliferative disorder.  

PubMed

The incidence and mortality of neoplasia in patients with primary immunodeficiencies exceed the anticipated rates in the normal population by approximately 100 to 300 times. Lymphoreticular malignancies account for the majority of tumors, although solid tumors, especially gastric carcinoma, occur with increased frequency as well. More than half of these neoplasms are diagnosed by ten years of age, except in patients with a later age of onset of immunodeficiency. Five primary immunodeficiency disorders with an increased risk of neoplasia are reviewed. PMID:7712652

Paller, A S

1995-01-01

251

Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome.  

PubMed Central

Virologic and immunologic studies were performed on five patients presenting with primary human immunodeficiency virus type 1 (HIV-1) infection. CD8+ cytotoxic T lymphocyte (CTL) precursors specific for cells expressing antigens of HIV-1 Gag, Pol, and Env were detected at or within 3 weeks of presentation in four of the five patients and were detected in all five patients by 3 to 6 months after presentation. The one patient with an absent initial CTL response had prolonged symptoms, persistent viremia, and low CD4+ T-cell count. Neutralizing antibody activity was absent at the time of presentation in all five patients. These findings suggest that cellular immunity is involved in the initial control of virus replication in primary HIV-1 infection and indicate a role for CTL in protective immunity to HIV-1 in vivo. PMID:8207839

Koup, R A; Safrit, J T; Cao, Y; Andrews, C A; McLeod, G; Borkowsky, W; Farthing, C; Ho, D D

1994-01-01

252

Neopterin in AIDS, other immunodeficiencies, and bacterial and viral infections  

Microsoft Academic Search

Summary An increase in total urinary neopterin was observed in 12 of 13 patients with acquired immunodeficiency syndrome (AIDS), seven of 13 patients with lymphadenopathy, one of six healthy homosexual males, seven of ten adult patients with staphylococcal pneumonia, 11 of 12 children with viral infections, four of seven children with bacterial infections, and 12 of 13 children with various

A. Niederwieser; P. Joller; R. Seger; N. Blau; A. Prader; J. D. Bettex; R. Lüthy; B. Hirschel; J. Schaedelin; U. Vetter

1986-01-01

253

Gastric adenocarcinoma in a patient with common variable immunodeficiency.  

PubMed

We describe a 46-year-old man with a 20-year history of common variable immunodeficiency (CVID) who developed adenocarcinoma of the stomach. Although the mechanism is still debated, there is an increased frequency of gastric adenocarcinoma of the stomach in patients with CVID. Consequently, gastric complaints in patients with CVID should be pursued aggressively. PMID:7820019

Cox, J E; Ott, D J

1994-01-01

254

A case of common variable immunodeficiency presenting with furunculosis.  

PubMed

Common variable immunodeficiency (CVID) is the most prevalent of the primary immunodeficiencies, and is characterised by low IgG and IgA, and sometimes IgM. There is some evidence of genetic susceptibility, with 20% of patients having a dominantly inherited disorder with variable expression. It is a heterogeneous disorder with protean manifestations, and as a result diagnosis is often delayed until the second or third decade, with resultant irreversible organ damage, in particular bronchiectasis. Effective treatment is available with regular 3-4-weekly infusions of immunoglobulin. The mechanism of the immunodeficiency has not yet been fully elucidated. The majority of patients present with recurrent sinopulmonary infection, however, this is a multisystem disorder and thus presents to physicians in diverse specialties including dermatology. Other clinical features of the disorder include gastrointestinal problems, granulomatous inflammation, cutaneous features, unusual presentations of enteroviral and mycoplasma infection, an increased incidence of autoimmunity, and a predisposition to lymphoma and stomach cancer. Therefore a knowledge of the disorder and appropriate suspicion by all clinicians of the possibility of such rare problems and a consequent low threshold for performing relevant investigations is imperative in allowing early recognition and instituting effective treatment. We describe a case of CVID identified when the patient developed widespread skin infection, fever and malaise. This case is an important example of a possible presentation of CVID within the dermatology clinic and demonstrates that maintaining a high level of clinical suspicion is essential for the diagnosis of the rare primary immunodeficiencies. PMID:12174114

Sidwell, R U; Ibrahim, M A A; Bunker, C B

2002-08-01

255

The German national registry for primary immunodeficiencies (PID)  

PubMed Central

In 2009, a federally funded clinical and research consortium (PID–NET, http://www.pid-net.org) established the first national registry for primary immunodeficiencies (PID) in Germany. The registry contains clinical and genetic information on PID patients and is set up within the framework of the existing European Database for Primary Immunodeficiencies, run by the European Society for Primary Immunodeficiencies. Following the example of other national registries, a central data entry clerk has been employed to support data entry at the participating centres. Regulations for ethics approvals have presented a major challenge for participation of individual centres and have led to a delay in data entry in some cases. Data on 630 patients, entered into the European registry between 2004 and 2009, were incorporated into the national registry. From April 2009 to March 2012, the number of contributing centres increased from seven to 21 and 738 additional patients were reported, leading to a total number of 1368 patients, of whom 1232 were alive. The age distribution of living patients differs significantly by gender, with twice as many males than females among children, but 15% more women than men in the age group 30 years and older. The diagnostic delay between onset of symptoms and diagnosis has decreased for some PID over the past 20 years, but remains particularly high at a median of 4 years in common variable immunodeficiency (CVID), the most prevalent PID. PMID:23607573

Gathmann, B; Goldacker, S; Klima, M; Belohradsky, B H; Notheis, G; Ehl, S; Ritterbusch, H; Baumann, U; Meyer-Bahlburg, A; Witte, T; Schmidt, R; Borte, M; Borte, S; Linde, R; Schubert, R; Bienemann, K; Laws, H-J; Dueckers, G; Roesler, J; Rothoeft, T; Kruger, R; Scharbatke, E C; Masjosthusmann, K; Wasmuth, J-C; Moser, O; Kaiser, P; Gross-Wieltsch, U; Classen, C F; Horneff, G; Reiser, V; Binder, N; El-Helou, S M; Klein, C; Grimbacher, B; Kindle, G

2013-01-01

256

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

257

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

258

Sino-orbital Aspergillosis in Acquired Immunodeficiency Syndrome  

Microsoft Academic Search

Objective: To describe the clinical features, causes, im- aging characteristics, treatment, and outcome of pa- tients with the acquired immunodeficiency syndrome (AIDS) and sino-orbital aspergillosis. Design: Records of 5 patients were reviewed. Results of imaging and histopathologic examinations and clinical courses of the patients were studied. Results: There were 3 women and 2 men (mean age, 34.0 years). All had

Thomas E. Johnson; Roy R. Casiano; Jan W. Kronish; David T. Tse; Melissa Meldrum; Warren Chang

1999-01-01

259

Human Immunodeficiency Virus Type 2 Infection in Spain  

Microsoft Academic Search

SummaryThe first cases of human immunodeficiency virus type 2 (HIV-2) infection in Spain were identified in 1988, in 3 African immigrants living in Barcelona. Since then, up to December 1998, 92 individuals with HIV-2 infection have been reported in Spain. Most are adult men, infected through heterosexual contacts, originating from West African countries, and currently living in the largest urban

Ana Machuca; Vincent Soriano; Mayte Gutiérrez; Africa Holguín; Antonio Aguilera; Estrella Caballero; Gustavo Cilla

1999-01-01

260

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

261

Human Immunodeficiency Virus in Correctional Facilities: A Review  

Microsoft Academic Search

It is estimated that up to one-fourth of the people living with human immunodeficiency virus (HIV) infection in the United States pass through a correctional facility each year. The majority of persons who enter a correctional facility today will return home in the near future. Most inmates with HIV infection acquire it in the outside community; prison does not seem

Anne Spaulding; Becky Stephenson; Grace Macalino; William Ruby; Jennifer G. Clarke; Timothy P. Flanigan

2002-01-01

262

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

263

Intracellular Accumulation of Human Immunodeficiency Virus Protease Inhibitors  

Microsoft Academic Search

Intracellular accumulation of the protease inhibitors (PIs) saquinavir (SQV), ritonavir (RTV), and indinavir (IDV) was determined in 50 human immunodeficiency virus-positive patients. Following extraction, PIs were quantified by mass spectrometry. Paired plasma and intracellular samples were collected over a full dosing interval from patients (13 on SQV, 6 on RTV, 8 on IDV, 16 on SQV plus RTV, 7 on

Saye H. Khoo; Patrick G. Hoggard; Ian Williams; E. Rhiannon Meaden; Philippa Newton; Edmund G. Wilkins; Alan Smith; John F. Tjia; Judy Lloyd; Kevin Jones; Nick Beeching; Peter Carey; Barry Peters; David J. Back

2002-01-01

264

Self Antigen Prognostic for Human Immunodeficiency Virus Disease Progression  

Microsoft Academic Search

We have recently found that an extracellular protein, 1 proteinase inhibitor (1PI; 1 antitrypsin), is re- quired for in vitro human immunodeficiency virus (HIV) infectivity outcome. We show here in a study of HIV- seropositive patients that decreased viral load is significantly correlated with decreased circulating 1PI. In the asymptomatic category of HIV disease, 100% of patients manifest deficient levels

CYNTHIA L. BRISTOW; HIRENKUMAR PATEL; ROLAND R. ARNOLD

2001-01-01

265

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.

266

Nutritional management of the dialysis patient with acquired immunodeficiency syndrome  

Microsoft Academic Search

•Objective: To review the current literature so that appropriate nutritional guidelines, interventions, and management for the dialysis patient with acquired immunodeficiency syndrome (AIDS) can be determined.•Data: Relevant English language articles were identified via MEDLINE search (1980 to 1995), Relevant texts also were reviewed. Additional references were selected from bibliographies of identified articles and texts.•Study selection: All selected articles and texts

Dodi Plourd

1995-01-01

267

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

268

Protein-Protein Interactions in Human Immunodeficiency Virus  

Microsoft Academic Search

Treatment for AIDS has proven difficult due to the high mutation rates of the genes of the causative human immunodeficiency virus (HIV). Current treatments for HIV are generally targeted at the enzymes reverse transcriptase and protease, but resistance is common. The discovery of new drug targets could lead to more effective treatments or even a cure for AIDS. To this

John M. Schmidt; Judith Klein-Seetharaman

269

Genetic Diversity of Argentine Isolates of Feline Immunodeficiency Virus  

Microsoft Academic Search

We report the nucleotide sequence and genetic diversity of part of the envelope (env) gene of four strains of feline immunodeficiency virus (FIV) isol- ated from Argentine domestic cats. The DNA enco- ding the V3 to V5 regions of the env gene of the FIV isolates were amplified by PCR, cloned and sequ- enced. Phylogenetic analysis revealed that the Argentine

Marcelo R. Pecoraro; K. Tomonaga; T. Miyazawa; Y. Kawaguchi; S. Sugita; Y. Tohya; C. Kai; M. E. Etcheverrigaray; T. Mikami

1996-01-01

270

Human Immunodeficiency Virus Risk Behavior Among Female Substance Abusers  

Microsoft Academic Search

HIV is an increasingly critical and costly health problem for American women. Substance use plays a major role in human immunodeficiency virus (HIV) infection in women. There are several plausible explanations for the association between substance use and HIV risk behavior. Pregnant substance abusers are a population deserving special attention given the prevalence of risk behavior in this population and

Susan E. Ramsey; Kathryn M. Bell; Patricia A. Engler

2010-01-01

271

Coreceptor Specificity of Temporal Variants of Simian Immunodeficiency Virus Mne  

Microsoft Academic Search

The simian immunodeficiency virus (SIV) Mne envelope undergoes genetic changes that alter tropism, syncytium-inducing capacity, and antigenic properties of the emerging variant virus population during the course of an infection. Here we investigated whether the mutations in envelope of SIVMne also influence coreceptor usage. The data demonstrate that the infecting macrophage-tropic SIVMne clone as well as the envelope vari- ants

JASON T. KIMATA; JOHN J. GOSINK; VINEET N. KEWALRAMANI; LYLE M. RUDENSEY; DAN R. LITTMAN; JULIE OVERBAUGH

1999-01-01

272

Lymphocyte characteristics in children with common variable immunodeficiency  

Microsoft Academic Search

The diagnosis of common variable immunodeficiency (CVID) is reserved for patients who suffer from undefined B cell dysfunction. Division of the CVID population into subgroups enables research for underlying disease causes. We studied clinical features and lymphocyte characteristics in 38 children with CVID and compared them to 30 children with less severe antibody deficiencies (e.g. specific antibody deficiency combined with

Annick A. J. M. van de Ven; Lisette van de Corput; Cornelis M. van Tilburg; Kiki Tesselaar; Rogier van Gent; Elisabeth A. M. Sanders; Marianne Boes; Andries C. Bloem; Joris M. van Montfrans

2010-01-01

273

Alopecia totalis and vitiligo in common variable immunodeficiency  

Microsoft Academic Search

Three cases of severe and irreversible alopecia occurring in patients with common variable immunodeficiency are described. In all three cases, hair loss developed after the diagnosis of immune deficiency; one of the patients also had extensive vitiligo. A fourth patient had vitiligo in the absence of alopecia. No change in the alopecia or vitiligo was noted in any patient as

G. Spickett; A. G. Prentice; T. Wallington; A. D. Webster; H. Chapel

1991-01-01

274

Clinical and laboratory aspects of common variable immunodeficiency  

Microsoft Academic Search

Common variable immunodeficiency (CVID) is an immunological disorder characterized by defective an- tibody production, recurrent infections, most notably of the respiratory tract, autoimmune phenomena and cancer. Some CVID patients may also present disturbances of the cellular immune response such as a decrease in the number and proportion of different lymphocyte populations, diminished lymphoproliferative response to mitogens and antigens, altered production

Cristina M. Kokron; Paolo R. Errante; Myrthes T. Barros; Gisele V. Baracho; Maristela M. Camargo; Jorge Kalil; Luiz V. Rizzo

2004-01-01

275

Common variable immunodeficiency: The power of co-stimulation  

Microsoft Academic Search

Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immune deficiency in adults. CVID is characterized by the sequelae of an antibody deficiency syndrome: an impaired terminal B cell differentiation results in hypogammaglobulinemia and susceptibility to recurrent infections by encapsulated bacteria. The clinical course of CVID is complicated by a plethora of systemic immunopathology, including autoimmunity, lymphoproliferation, malignancy and

Ulrich Salzer; Bodo Grimbacher

2006-01-01

276

Gamma Interferon Primes Productive Human Immunodeficiency Virus Infection in Astrocytes  

Microsoft Academic Search

Considerable controversy exists over whether astrocytes can support human immunodeficiency virus (HIV) infection. We evaluated the impact of three cytokines critical to the development of HIV neuropathogenesis, gamma interferon (IFN-), granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha, on priming astrocytes for HIV infection. We demonstrate that IFN- was the most potent in its ability to facilitate substantial productive HIV

Deborah Carroll-Anzinger; Lena Al-Harthi

2006-01-01

277

Molecular characterization and heterogeneity of feline immunodeficiency virus isolates  

Microsoft Academic Search

Summary We have molecularly cloned the complete genomic DNA of TM2 strain of feline immunodeficiency virus (FIV) isolated in Japan and compared its nucleotide and the deduced amino acid sequence with those of previously described U.S. isolates, FIV Petaluma and FIV PPR. The infectious molecular clone of FIV TM2 is different from FIV Petaluma in host cell range; the clone

N. Maki; T. Miyazawa; M. Fukasawa; A. Hasegawa; M. Hayami; K. Miki; T. Mikami

1992-01-01

278

Intestinal infections in patients with acquired immunodeficiency syndrome  

Microsoft Academic Search

We studied prospectively 132 patients with acquired immunodeficiency syndrome to define the spectrum of enteric pathogens during this disease, with special reference to the correlation between the lesions, the infections, and the symptoms. Forty-four percent of the patients harbored at least one enteric pathogen: the most frequently recovered were Cryptosporidium (28), cytomegalovirus (16), Entamoeba histolytica (13), Giardia lamblia (9), and

E. René; C. Marche; B. Regnier; A. G. Saimot; J. L. Vilde; C. Perrone; C. Michon; M. Wolf; Th. Chevalier; Th. Vallot; F. Brun-Vesinet; B. Pangon; A. M. Deluol; F. Camus; C. Roze; J. P. Pignon; M. Mignon; S. Bonfils

1989-01-01

279

Tiered Categorization of a Diverse Panel of HIV-1 Env Pseudoviruses for Assessment of Neutralizing Antibodies ?  

PubMed Central

The restricted neutralization breadth of vaccine-elicited antibodies is a major limitation of current human immunodeficiency virus-1 (HIV-1) candidate vaccines. In order to permit the efficient identification of vaccines with enhanced capacity for eliciting cross-reactive neutralizing antibodies (NAbs) and to assess the overall breadth and potency of vaccine-elicited NAb reactivity, we assembled a panel of 109 molecularly cloned HIV-1 Env pseudoviruses representing a broad range of genetic and geographic diversity. Viral isolates from all major circulating genetic subtypes were included, as were viruses derived shortly after transmission and during the early and chronic stages of infection. We assembled a panel of genetically diverse HIV-1-positive (HIV-1+) plasma pools to assess the neutralization sensitivities of the entire virus panel. When the viruses were rank ordered according to the average sensitivity to neutralization by the HIV-1+ plasmas, a continuum of average sensitivity was observed. Clustering analysis of the patterns of sensitivity defined four subgroups of viruses: those having very high (tier 1A), above-average (tier 1B), moderate (tier 2), or low (tier 3) sensitivity to antibody-mediated neutralization. We also investigated potential associations between characteristics of the viral isolates (clade, stage of infection, and source of virus) and sensitivity to NAb. In particular, higher levels of NAb activity were observed when the virus and plasma pool were matched in clade. These data provide the first systematic assessment of the overall neutralization sensitivities of a genetically and geographically diverse panel of circulating HIV-1 strains. These reference viruses can facilitate the systematic characterization of NAb responses elicited by candidate vaccine immunogens. PMID:19939925

Seaman, Michael S.; Janes, Holly; Hawkins, Natalie; Grandpre, Lauren E.; Devoy, Colleen; Giri, Ayush; Coffey, Rory T.; Harris, Linda; Wood, Blake; Daniels, Marcus G.; Bhattacharya, Tanmoy; Lapedes, Alan; Polonis, Victoria R.; McCutchan, Francine E.; Gilbert, Peter B.; Self, Steve G.; Korber, Bette T.; Montefiori, David C.; Mascola, John R.

2010-01-01

280

Improbability of Effective Vaccination Against Human Immunodeficiency Virus Because of Its Intracellular Transmission and Rectal Portal of Entry  

NASA Astrophysics Data System (ADS)

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 bloodstream, 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.

Sabin, Albert B.

1992-09-01

281

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

282

A “tongue” of neutral composition  

Microsoft Academic Search

Both the thermosphere and the ionosphere react to forcing from the magnetospherically imposed ion convection pattern. A twin-celled, neutral convection pattern is set up that normally follows the ion convection pattern; however, unlike the ionosphere, the thermosphere takes a considerable time to react to geomagnetic forcing. In solar maximum conditions this reaction time can take 1–3h. The close relationship between

A. G. Burns; W. Wang; T. L. Killeen; S. C. Solomon

2004-01-01

283

Polarizability of neutral copper clusters.  

PubMed

Neutral copper clusters are characterized through their molecular structures, binding energy and electric dipole polarizability. It is shown that the mean and anisotropy of polarizability tensor are useful properties in the characterization and rationalization of reactivity and growth patterns in copper clusters. We also found a relationship between softness per atom and cubic root polarizability per atom which can be useful to get global softness in copper clusters. PMID:25149439

Jaque, Pablo; Toro-Labbé, Alejandro

2014-09-01

284

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

285

Radiative lifetimes of neutral erbium  

Microsoft Academic Search

Radiative lifetimes have been measured for 123 levels of neutral erbium using time-resolved laser-induced fluorescence on a slow beam of erbium atoms. Of the 123 levels, 56 are even parity and range in energy from 26 993 to 40 440 cm?1 and 67 are odd parity ranging from 16 070 to 38 401 cm?1. This set of Er i lifetimes

E A Den Hartog; J P Chisholm; J E Lawler

2010-01-01

286

Radiative lifetimes of neutral erbium  

Microsoft Academic Search

Radiative lifetimes have been measured for 123 levels of neutral erbium using time-resolved laser-induced fluorescence on a slow beam of erbium atoms. Of the 123 levels, 56 are even parity and range in energy from 26 993 to 40 440 cm-1 and 67 are odd parity ranging from 16 070 to 38 401 cm-1. This set of Er i lifetimes

E. A. Den Hartog; J. P. Chisholm; J. E. Lawler

2010-01-01

287

Radiative lifetimes of neutral cerium  

Microsoft Academic Search

Radiative lifetimes, accurate to ±5%, have been measured for 153 levels of neutral cerium using time-resolved laser-induced fluorescence (TRLIF) on a slow beam of cerium atoms. Of the 153 levels studied, 150 are even parity and 3 are odd parity. The levels range in energy from 16 869 to 28 557 cm-1. This set of Ce I lifetimes is much

E. A. Den Hartog; K. P. Buettner; J. E. Lawler

2009-01-01

288

Radiative lifetimes of neutral cerium  

Microsoft Academic Search

Radiative lifetimes, accurate to ±5%, have been measured for 153 levels of neutral cerium using time-resolved laser-induced fluorescence (TRLIF) on a slow beam of cerium atoms. Of the 153 levels studied, 150 are even parity and 3 are odd parity. The levels range in energy from 16 869 to 28 557 cm?1. This set of Ce I lifetimes is much

E A Den Hartog; K P Buettner; J E Lawler

2009-01-01

289

Optimization of neutral atom imagers  

NASA Astrophysics Data System (ADS)

: 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 80°. 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. Work was supported by grant ACT-05-40 from the ESTO office of NASA

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

2008-12-01

290

Human immunodeficiency virus type-1 reverse transcriptase and ribonuclease H as substrates of the viral protease.  

PubMed Central

A study has been made of the susceptibility of recombinant constructs of reverse transcriptase (RT) and ribonuclease H (RNase H) from human immunodeficiency virus type 1 (HIV-1) to digestion by the HIV-1 protease. At neutral pH, the protease attacks a single peptide bond, Phe440-Tyr441, in one of the protomers of the folded, active RT/RNase H (p66/p66) homodimer to give a stable, active heterodimer (p66/p51) that is resistant to further hydrolysis (Chattopadhyay, D., et al., 1992, J. Biol. Chem. 267, 14227-14232). The COOH-terminal p15 fragment released in the process, however, is rapidly degraded by the protease by cleavage at Tyr483-Leu484 and Tyr532-Leu533. In marked contrast to this p15 segment, both p66/p51 and a folded RNase H construct are stable to breakdown by the protease at neutral pH. It is only at pH values around 4 that these latter proteins appear to unfold and, under these conditions, the heterodimer undergoes extensive proteolysis. RNase H is also hydrolyzed at low pH, but cleavage takes place primarily at Gly436-Ala437 and at Phe440-Tyr441, and only much more slowly at residues 483, 494, and 532. This observation can be reconciled by inspection of crystallographic models of RNase H, which show that residues 483, 494, and 532 are relatively inaccessible in comparison to Gly436 and Phe440. Our results fit a model in which the p66/p66 homodimer exists in a conformation that mirrors that of the heterodimer, but with a p15 segment on one of the protomers that is structurally disordered to the extent that all of its potential HIV protease cleavage sites are accessible for hydrolysis. PMID:7507754

Tomasselli, A. G.; Sarcich, J. L.; Barrett, L. J.; Reardon, I. M.; Howe, W. J.; Evans, D. B.; Sharma, S. K.; Heinrikson, R. L.

1993-01-01

291

Is neutralization necessary for criminal behavior?  

Microsoft Academic Search

Criminological theories currently place much emphasis on neutralization of norms, i.e., extension or distortion of norms to allow guilt?free infraction, as a key element in criminal behavior. This paper examines the major assumptions underlying the neutralization thesis and a critical alternative thesis, which argues that criminal beliefs rather than neutralizations permit criminal actions. Analysis of data from a sample of

Joseph F. Sheley

1980-01-01

292

The delusions of net neutrality Andrew Odlyzko  

E-print Network

The delusions of net neutrality Andrew Odlyzko School of Mathematics, University of Minnesota Abstract. Service providers argue that if net neutrality is not enforced, they will have su evolution. But what if they do get their wish, net neutrality is consigned to the dustbin, and they do build

Odlyzko, Andrew M.

293

The delusions of net neutrality Andrew Odlyzko  

E-print Network

The delusions of net neutrality Andrew Odlyzko School of Mathematics, University of Minnesota Abstract. Service providers argue that if net neutrality is not enforced, they will have sufficient evolution. But what if they do get their wish, net neutrality is consigned to the dustbin, and they do build

Odlyzko, Andrew M.

294

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

295

Adaptation of the Human Immunodeficiency Virus Type 1 Envelope Glycoproteins to New World Monkey Receptors?  

PubMed Central

Human immunodeficiency virus type 1 (HIV-1) infection encounters an early block in the cells of New World monkeys because the CD4 receptor does not efficiently support HIV-1 entry. We adapted HIV-1(NL4-3) and HIV-1(KB9), two HIV-1 variants with different envelope glycoproteins, to replicate efficiently in cells expressing the CD4 and CXCR4 proteins of the common marmoset, a New World monkey. The HIV-1(NL4-3) adaptation involves three gp120 changes that result in a specific increase in affinity for the marmoset CD4 glycoprotein. The already high affinity of the HIV-1(KB9) envelope glycoproteins for marmoset CD4 did not significantly change as a result of the adaptation. Instead, changes in the gp120 variable loops and gp41 ectodomain resulted in improved replication in cells expressing the marmoset receptors. HIV-1(KB9) became relatively sensitive to neutralization by soluble CD4 and antibodies as a result of the adaptation. These results demonstrate the distinct mechanistic pathways by which the HIV-1 envelope glycoproteins can adapt to less-than-optimal CD4 molecules and provide HIV-1 variants that can overcome some of the early blocks in New World monkey cells. PMID:17959679

Pacheco, Beatriz; Basmaciogullari, Stephane; LaBonte, Jason A.; Xiang, Shi-Hua; Sodroski, Joseph

2008-01-01

296

Serological responses in chimpanzees inoculated with human immunodeficiency virus glycoprotein (gp120) subunit vaccine  

SciTech Connect

The major envelope glycoprotein of a human immunodeficiency virus (HIV) has been purified and was utilized as a prototype vaccine in chimpanzees. The 120,000-dalton glycoprotein (gp120) was purified from membranes of human T-lymphotropic virus (HTLV)-IIIB-infected cells and the final preparation contained low levels to no detectable HTLV-IIIB core antigen (p24) and low levels of endotoxin. Chimpanzees inoculated with gp120 responded by developing antibodies that precipitated radiolabeled gp120 and neutralized in vitro infection of HTLV-IIIB. Antibodies to HTLV-IIIB p24 were not detected in the gp120-immunized chimpanzees. Peripheral blood leukocytes from the vaccinated animals were examined for T4/sup +/ and T8/sup +/ cells, and no decrease in the T4/T8 ratio was found, indicating that immunization with a ligand (gp120) that binds to T4 has not detectable adverse effect on the population of T4/sup +/ cells. The only current animal model that can be reproducibly infected with HIV is the chimpanzee. Immunization of chimpanzees with HIV proteins will provide an experimental system for testing the effectiveness of prototype vaccines for preventing HIV infection in vivo.

Arthur, L.O.; Pyle, S.W.; Nara, P.L.; Bess, J.W. Jr.; Gonda, M.A.; Kelliher, J.C.; Gilden, R.V.; Robey, W.G.; Bolognesi, D.P.; Gallo, R.C.

1987-12-01

297

Network neutrality, search neutrality, and the never-ending conflict between efficiency and fairness  

E-print Network

on society mean that no fixed set of rules can work indefinitely. Should net neutrality or some similar set of speculation. On the other hand, net neutrality and its close relatives, such as common carriage neutral communication infrastructure can be viable. And if it is not, just how far from net neutrality

Odlyzko, Andrew M.

298

Network neutrality, search neutrality, and the neverending conflict between e#ciency and fairness  

E-print Network

on society mean that no fixed set of rules can work indefinitely. Should net neutrality or some similar set of speculation. On the other hand, net neutrality and its close relatives, such as common carriage neutral communication infrastructure can be viable. And if it is not, just how far from net neutrality

Odlyzko, Andrew M.

299

Neutral hydrogen in cometary comas.  

NASA Technical Reports Server (NTRS)

The strong L alpha radiation observed recently in comets Tago-Sato-Kosaka and Bennett can be explained in terms of the resonant scattering of solar L alpha radiation on neutral hydrogen formed by the photodissociation of H2O which is vaporized from a nucleus having an ice core. A complete hydrodynamic description of an atmosphere composed of H2O and its daughter products OH, H and O coupled through frictional interaction as well as production and loss processes is given. Numerical results are computed in a typical case, and it is found that a temperature of about 3000 K for the cometary atmosphere provides the best fit with observation.

Mendis, D. A.; Holzer, T. E.; Axford, W. I.

1972-01-01

300

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

301

Distinct replicative and cytopathic characteristics of human immunodeficiency virus isolates.  

PubMed Central

According to their capacity to replicate in vitro, human immunodeficiency virus (HIV) isolates can be divided into two major groups, rapid/high and slow/low. Rapid/high viruses can easily be transmitted to a variety of cell lines of T-lymphoid (CEM, H9, and Jurkat) and monocytoid (U937) origin. In contrast, slow/low viruses replicate transiently, if at all, in these cell lines. Except for a few isolates, the great majority of slow/low viruses replicate in peripheral blood mononuclear cells and Jurkat-tatIII cells constitutively expressing the tatIII gene of HIV-1. The viruses able to replicate efficiently cause syncytium formation and are regularly isolated from immunodeficient patients. Poorly replicating HIV isolates, often obtained from individuals with no or mild disease, show syncytium formation and single-cell killing simultaneously or, with some isolates, cell killing only. Images PMID:2459416

Fenyo, E M; Morfeldt-Manson, L; Chiodi, F; Lind, B; von Gegerfelt, A; Albert, J; Olausson, E; Asjo, B

1988-01-01

302

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

303

Thirty years of the human immunodeficiency virus epidemic and beyond.  

PubMed

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

2013-12-01

304

Severe combined immunodeficiency resulting from mutations in MTHFD1.  

PubMed

Folate and vitamin B(12) metabolism are essential for de novo purine synthesis, and several defects in these pathways have been associated with immunodeficiency. Here we describe the occurrence of severe combined immunodeficiency (SCID) with megaloblastic anemia, leukopenia, atypical hemolytic uremic syndrome, and neurologic abnormalities in which hydroxocobalamin and folate therapy provided partial immune reconstitution. Whole exome sequencing identified compound heterozygous mutations in the MTHFD1 gene, which encodes a trifunctional protein essential for processing of single-carbon folate derivatives. We now report the immunologic details of this novel genetic cause of SCID and the response to targeted metabolic supplementation therapies. This finding expands the known metabolic causes of SCID and presents an important diagnostic consideration given the positive impact of therapy. PMID:23296427

Keller, Michael D; Ganesh, Jaya; Heltzer, Meredith; Paessler, Michele; Bergqvist, A G Christina; Baluarte, H Jorge; Watkins, David; Rosenblatt, David S; Orange, Jordan S

2013-02-01

305

Recovery of the human immunodeficiency virus from fibreoptic bronchoscopes.  

PubMed Central

Ten bronchoscopes that had been used on patients with the acquired immunodeficiency syndrome were sampled to determine the nature and extent of microbial contamination. Samples were taken by irrigating the suction biopsy channel with modified viral transport medium and by swabbing the insertion tube. Sampling was repeated after they had been cleaned in detergent and after two minutes' disinfection in 2% alkaline glutaraldehyde. Before being cleaned the seven bronchoscopes tested by polymerase chain reaction were contaminated with the human immunodeficiency virus, though infectivity and antigen assays gave negative results. Other organisms identified were hepatitis B virus (1), commensal bacteria (9), and Pneumocystis carinii (4). Mean bacterial contamination was 2.27 log colony forming organisms per millilitre. Cleaning the bronchoscope before disinfection removed all detectable contaminants with a reduction in bacterial growth of up to 8 log colony forming units/ml. PMID:1858078

Hanson, P J; Gor, D; Clarke, J R; Chadwick, M V; Gazzard, B; Jeffries, D J; Gaya, H; Collins, J V

1991-01-01

306

Immunopathogenesis of Simian Immunodeficiency Virus (SIV) Infection in Nonhuman Primates  

Microsoft Academic Search

Purpose of review—Soon after the discovery of HIV-infected humans, rhesus macaques in a colony at the New England Primate Research Center showed similar signs of a progressive immune suppression. The discovery of the Simian Immunodeficiency Virus (SIV)-associated disease opened the door to study an AIDS-like illness in nonhuman primates (NHP). Even after three decades, this animal model remains an invaluable

Joern E. Schmitz; Birgit Korioth-Schmitz

2013-01-01

307

Endocrinopathies in children infected with human immunodeficiency virus.  

PubMed

Endocrine changes (including adrenal insufficiency, disorders of growth and puberty, thyroid dysfunction, metabolic abnormalities and osteopenia) accompany human immunodeficiency virus (HIV) infection in pediatric patients. The cause of these changes is multifactorial and includes direct viral effects of HIV, and effects of antiretroviral therapy. These effects may be of particular importance in childhood given the critical developmental processes that occur during this time period and the likelihood of prolonged exposure to the virus and medications. PMID:25169569

Loomba-Albrecht, Lindsey A; Bregman, Thea; Chantry, Caroline J

2014-09-01

308

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

309

Human Immunodeficiency Virus: Resistance to Antiretroviral Drugs in Developing Countries  

Microsoft Academic Search

\\u000a This chapter reviews issues central to understanding the emergence and transmission of drug-resistant human immunodeficiency\\u000a virus (HIV) and its impact on developing countries. We first give an overview of HIV, HIV treatment using antiretroviral drugs,\\u000a and access to treatment in developing countries. Then we review current understanding of the impact of adherence and treatment\\u000a interruption on the emergence of resistance

Rebecca F. Baggaley; Maya L. Petersen; Marcelo A. Soares; Marie-Claude Boily; Francisco I. Bastos

310

Human Immunodeficiency Virus and the New CDC Guidelines  

Microsoft Academic Search

Since the Human Immunodeficiency Virus (HIV) was first recognized in the United States in the early 1980's, science and medicine have made significant progress managing HIV. However, this progress may have left many youth with little personal knowledge or experience of the devastating effects of the disease. In Missouri, an estimated 10,000 individuals are living with HIV\\/AIDS and every year

Daryl A. Lynch

2007-01-01

311

Avascular necrosis of bone in human immunodeficiency virus infected patients  

Microsoft Academic Search

The objective of this article was to delineate the causes of avascular necrosis (AVN) in patients with human immunodeficiency virus (HIV). HIV-infected patients with pain in large joints were prospectively screened. Patients had radiographs and magnetic resonance imaging of their affected joints. Serum lipids, anticardiolipin antibody levels (IgG, IgM), and hemoglobin electrophoresis were performed on all patients who had radiographic

Marcia F Blacksin; Patricia C Kloser; Jocelyn Simon

1999-01-01

312

Colonization of Congenitally Immunodeficient Mice with Probiotic Bacteria  

Microsoft Academic Search

We assessed the capacity of four probiotic bacteria (Lactobacillus acidophilus, Lactobacillus reuteri, Lactoba- cillus 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-euthy- mic (bg\\/bg-nu\\/1) mice. The bacteria colonized and persisted, in pure culture, in the alimentary tracts of both mouse strains for

R. DOUG WAGNER; THOMAS WARNER; LISA ROBERTS; JEFFREY FARMER; EDWARD BALISH

1997-01-01

313

Isolated adrenocorticotropic hormone deficiency associated with common variable immunodeficiency  

Microsoft Academic Search

A 14-year-old girl has been suffering from an isolated adrenocorticotropin hormone (ACTH) deficiency with secondary glucocorticoid deficiency and common variable immunodeficiency since the age of 6.6 years. Human corticotropin releasing hormone administration did not increase ACTH and cortisol levels, strongly suggesting a pituitary deficiency. Despite the profound humoral defect, severe infections have never developed and the antibody response to herpes

P. A. Tovo; R. Lala; S. martino; G. Pastorelli; C. De Sanctis

1991-01-01

314

Primary immunodeficiency diagnosed at autopsy: a case report  

PubMed Central

Background DiGeorge syndrome may manifest as severe immunodeficiency diagnosed at infancy. The diagnosis of primary immunodeficiency is based on characteristic clinical features, immunophenotyping by flow cytometry, molecular diagnostics and functional lymphocyte evaluation. At autopsy, gross evaluation, conventional histology and immunohistochemistry may be useful for the diagnosis of primary immunodeficiency. This case report illustrates the application of autopsy and immunohistochemistry in the diagnosis of DiGeorge syndrome. Case presentation A four-month-old African female infant died while undergoing treatment at Kenyatta National Hospital, a Referral and Teaching Hospital in Nairobi, Kenya. She presented with a month’s history of recurrent respiratory infections, a subsequent decline in the level of consciousness and succumbed to her illness within four days. Her two older siblings died following similar circumstances at ages 3 and 5 months respectively. Autopsy revealed thymic aplasia, bronchopneumonia and invasive brain infection by Aspergillus species. Microbial cultures of cerebrospinal fluid, jejunal contents, spleen and lung tissue revealed multi drug resistant Klebsiella spp, Pseudomonas spp, Serratia spp and Escherichia coli. Immunohistochemistry of splenic tissue obtained from autopsy confirmed reduction of T lymphocytes. Conclusion Use of immunohistochemistry on histological sections of tissues derived from autopsy is a useful adjunct for post mortem diagnosis of DiGeorge syndrome. PMID:24996427

2014-01-01

315

Species-Specific, Postentry Barriers to Primate Immunodeficiency Virus Infection  

PubMed Central

By using replication-defective vectors derived from human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIVmac), and murine leukemia virus (MuLV), all of which were pseudotyped with the vesicular stomatitis virus (VSV) G glycoprotein, the efficiency of postentry, early infection events was examined in target cells of several mammalian species. Titers of HIV-1 vectors were significantly lower than those of SIVmac and MuLV vectors in most cell lines and primary cells from Old World monkeys. By contrast, most New World monkey cells exhibited much lower titers for the SIVmac vector compared with those of the HIV-1 vector. Prosimian cells were resistant to both HIV-1 and SIVmac vectors, although the MuLV vector was able to infect these cells. Cells from other mammalian species were roughly equivalent in susceptibility to the three vectors, with the exception of rabbit cells, which were specifically resistant to the HIV-1 vector. The level of HIV-1 vector expression was very low in transduced cells of rodent, rabbit, cow, and pig origin. Early postentry restriction of primate immunodeficiency virus infection exhibits patterns largely coincident with species borders and applies to diverse cell types within an individual host, suggesting the involvement of species-specific, widely expressed cellular factors. PMID:10559316

Hofmann, Wolfgang; Schubert, David; LaBonte, Jason; Munson, Linda; Gibson, Susan; Scammell, Jonathan; Ferrigno, Paul; Sodroski, Joseph

1999-01-01

316

Occurrence of intestinal microsporidia in immunodeficient patients in Poland.  

PubMed

Microsporidial infections may be asymptomatic in immunocompetent hosts, but can be severe and disseminated in HIV/AIDS patients, children, the elderly, or in immunocompromised individuals, including those with primary or medically-induced immunodeficiencies. 209 faecal samples were collected from 80 clinical patients, with or without abdominal symptoms, and tested for the presence of the parasites. Microsporidia were found in 10 of the 80 patients (12.5%) using trichrom staining of faecal smears and/or PCR. Encephalitozoon intestinalis and 1 unidentified species were identified in 2 of the 32 children with primary immunodeficiencies (6%), presenting with diarrhoea, including one co-infection with Cryptosporidium meleagridis. In the group of patients with medically-induced immunosuppression (transplant recipients), 8 of the 48 patients (17%) were tested positive for microsporidia. Thus, these pathogens should be taken into account when the other etiological agents cannot be found in diarrheic patients with PIDs or undergoing immunosuppressive treatment before or after transplantation. This article presents the results of the first epidemiological study on the occurrence and prevalence of microsporidia in patients with primary and secondary immunodeficiency in Poland. PMID:24959769

Bednarska, Ma?gorzata; Bajer, Anna; Si?ski, Edward; Wolska-Ku?nierz, Beata; Samoli?ski, Boles?aw; Graczyk, Thaddeus K

2014-01-01

317

Common variable immunodeficiency and autoimmunity--an inconvenient truth.  

PubMed

Coexisting morbidities in CVID include bronchiectasis, autoimmunity and malignancies. The incidence of autoimmune disease in CVID patients may approach 20% of cases. The most common autoimmune disease found in CVID patients is autoimmune cytopenia, but rheumatoid arthritis, lupus, and now primary biliary cirrhosis have also been reported. The coexistence of immunodeficiency and autoimmunity appears paradoxical, since one represents a hypoimmune state and the other a hyperimmune state. However, this paradox may not actually be all that implausible due to the complex nature of immune cells, signaling pathways and their interactions. The cellular alterations in combined variable immunodeficiency include a range of T and B cell abnormalities. Selective immune derangements found in CVID include a downregulation of regulatory T cells (Treg cells), accelerated T cell apoptosis, abnormal cytokine production secondary to cytokine gene polymorphisms and increased autoreactive B cell production. The impact of these abnormalities on T and B cell interaction may not only explain the immunodeficiency but also the development of autoimmunity in select groups of patients with CVID. The variability in the clinical manifestations of CVID as a result of this immune interaction suggests that CVID is not one disease but many. This is important because it follows that the treatment of CVID may not always be the same, but may need to be directed specifically towards each individual patient. PMID:24747700

Xiao, Xiao; Miao, Qi; Chang, Christopher; Gershwin, M Eric; Ma, Xiong

2014-08-01

318

Primary Immunodeficiency Diseases: An Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency  

PubMed Central

We report the updated classification of primary immunodeficiency diseases, compiled by the ad hoc Expert Committee of the International Union of Immunological Societies. As compared to the previous edition, more than 15 novel disease entities have been added in the updated version. For each disorders, the key clinical and laboratory features are provided. This updated classification is meant to help in the diagnostic approach to patients with these diseases. PMID:22566844

Al-Herz, Waleed; Bousfiha, Aziz; Casanova, Jean-Laurent; Chapel, Helen; Conley, Mary Ellen; Cunningham-Rundles, Charlotte; Etzioni, Amos; Fischer, Alain; Franco, Jose Luis; Geha, Raif S.; Hammarstrom, Lennart; Nonoyama, Shigeaki; Notarangelo, Luigi Daniele; Ochs, Hans Dieter; Puck, Jennifer M.; Roifman, Chaim M.; Seger, Reinhard; Tang, Mimi L. K.

2011-01-01

319

Guidelines for national human immunodeficiency virus case surveillance, including monitoring for human immunodeficiency virus infection and acquired immunodeficiency syndrome. Centers for Disease Control and Prevention.  

PubMed

CDC recommends that all states and territories conduct case surveillance for human immunodeficiency virus (HIV) infection as an extension of current acquired immunodeficiency syndrome (AIDS) surveillance activities. The expansion of national surveillance to include both HIV infection and AIDS cases is a necessary response to the impact of advances in antiretroviral therapy, the implementation of new HIV treatment guidelines, and the increased need for epidemiologic data regarding persons at all stages of HIV disease. Expanded surveillance will provide additional data about HIV-infected populations to enhance local, state, and federal efforts to prevent HIV transmission, improve allocation of resources for treatment services, and assist in evaluating the impact of public health interventions. CDC will provide technical assistance to all state and territorial health departments to continue or establish HIV and AIDS case surveillance systems and to evaluate the performance of their surveillance programs. This report includes a revised case definition for HIV infection in adults and children, recommended program practices, and performance and security standards for conducting HIV/AIDS surveillance by local, state, and territorial health departments. The revised surveillance case definition and associated recommendations become effective January 1, 2000. PMID:10632297

1999-12-10

320

CD4+ T Cells Support Production of Simian Immunodeficiency Virus Env Antibodies That Enforce CD4-Dependent Entry and Shape Tropism In Vivo  

PubMed Central

CD4+ T cells rather than macrophages are the principal cells infected by human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) in vivo. Macrophage tropism has been linked to the ability to enter cells through CCR5 in conjunction with limiting CD4 levels, which are much lower on macrophages than on T cells. We recently reported that rhesus macaques (RM) experimentally depleted of CD4+ T cells before SIV infection exhibit extensive macrophage infection as well as high chronic viral loads and rapid progression to AIDS. Here we show that early-time-point and control Envs were strictly CD4 dependent but that, by day 42 postinfection, plasma virus of CD4+ T cell-depleted RM was dominated by Envs that mediate efficient infection using RM CCR5 independently of CD4. Early-time-point and control RM Envs were resistant to neutralization by SIV-positive (SIV+) plasma but became sensitive if preincubated with sCD4. In contrast, CD4-independent Envs were highly sensitive to SIV+ plasma neutralization. However, plasma from SIV-infected CD4+ T cell-depleted animals lacked this CD4-inducible neutralizing activity and failed to neutralize any Envs regardless of sCD4 pre-exposure status. Enhanced sensitivity of CD4-independent Envs from day 42 CD4+ T cell-depleted RM was also seen with monoclonal antibodies that target both known CD4-inducible and other Env epitopes. CD4 independence and neutralization sensitivity were both conferred by Env amino acid changes E84K and D470N that arose independently in multiple animals, with the latter introducing a potential N-linked glycosylation site within a predicted CD4-binding pocket of gp120. Thus, the absence of CD4 T cells results in failure to produce antibodies that neutralize CD4-independent Envs and CD4-pretriggered control Envs. In the absence of this constraint and with a relative paucity of CD4+ target cells, widespread macrophage infection occurs in vivo accompanied by emergence of variants carrying structural changes that enable entry independently of CD4. PMID:23824793

Francella, Nicholas; Gwyn, Sarah E.; Yi, Yanjie; Li, Bing; Xiao, Peng; Elliott, Sarah T. C.; Ortiz, Alexandra M.; Hoxie, James A.; Paiardini, Mirko; Silvestri, Guido; Derdeyn, Cynthia A.

2013-01-01

321

Phenomenology of neutral heavy leptons  

SciTech Connect

We continue our previous work on the flavor-conserving leptonic decays of the Z boson with neutral heavy leptons (NHL`s) in the loops by considering box, vertex, and self-energy diagrams for the muon decay. By inclusion of these loops (they contribute to the input parameter M{sub W}), we can probe the full parameter space spanned by the so-called flavor-conserving mixing parameters ee{sub mix},{mu}{mu}{sub mix},{tau}{tau}{sub mix}. We show that only two diagrams from each class (box, vertex, and self-energy) are important; further, after renormalization only two box diagrams {open_quotes}survive{close_quotes} as dominant. We compare the results of our analysis with the existing work in this field and conclude that flavor-conserving decays have certain advantages over traditionally considered flavor-violating ones. {copyright} {ital 1997} {ital The American Physical Society}

Kalyniak, P.; Melo, I. [Ottawa-Carleton Institute for Physics, Department of Physics, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, K1S 5B6 (CANADA)] [Ottawa-Carleton Institute for Physics, Department of Physics, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, K1S 5B6 (CANADA)

1997-02-01

322

Phenomenology of neutral heavy leptons  

NASA Astrophysics Data System (ADS)

We continue our previous work on the flavor-conserving leptonic decays of the Z boson with neutral heavy leptons (NHL's) in the loops by considering box, vertex, and self-energy diagrams for the muon decay. By inclusion of these loops (they contribute to the input parameter MW), we can probe the full parameter space spanned by the so-called flavor-conserving mixing parameters eemix,??mix,??mix. We show that only two diagrams from each class (box, vertex, and self-energy) are important; further, after renormalization only two box diagrams ``survive'' as dominant. We compare the results of our analysis with the existing work in this field and conclude that flavor-conserving decays have certain advantages over traditionally considered flavor-violating ones.

Kalyniak, Pat; Melo, I.

1997-02-01

323

Neutral-beam current drive in tokamaks  

SciTech Connect

The theory of neutral-beam current drive in tokamaks is reviewed. Experiments are discussed where neutral beams have been used to drive current directly and also indirectly through neoclassical effects. Application of the theory to an experimental test reactor is described. It is shown that neutral beams formed from negative ions accelerated to 500 to 700 keV are needed for this device.

Devoto, R.S.

1986-01-01

324

Nucleon neutral-current structure functions  

Microsoft Academic Search

The structure of the nucleon is studied by means of deep-inelastic neutrino-nucleon scattering at high energies through the weak neutral current. The neutrino-nucleon scattering events were observed in a 340-metric-ton fine-grained calorimeter exposed to a narrow-band (dichromatic) neutrino beam at Fermilab. The data sample after analysis cuts consists of 9200 charged-current and 3000 neutral-current neutrino and antineutrino events. The neutral-current

T. S. Mattison; J. Bofill; W. Busza; T. Eldridge; J. I. Friedman; S. Fuess; M. C. Goodman; H. W. Kendall; T. Lyons; R. Magahiz; A. Mukherjee; L. S. Osborne; R. Pitt; L. Rosenson; A. Sandacz; M. Tartaglia; F. E. Taylor; R. Verdier; J. S. Whitaker; G. P. Yeh; D. Bogert; R. Burnstein; J. G. Morfin; L. Stutte; J. K. Walker; M. Abolins; R. Brock; A. Cohen; J. Ernwein; D. Owen; J. Slate; H. Weerts

1990-01-01

325

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

326

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

327

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

328

Neutrality and curiosity: elements of technique.  

PubMed

In the past three decades, neutrality has come under increasing criticism. The idea that a psychoanalyst can leave himself out of the therapeutic exchange has come to be seen as either an impossible dream or a myth. We propose that examining neutrality through the lens of curiosity allows for a new appreciation of the ongoing and vital importance of this psychoanalytic attitude. Our hypothesis is that curiosity and neutrality are linked, and that to maintain a neutral stance, the analyst must be able to direct a relatively conflict-free curiosity toward the workings of the analysand's mind as well as his own. PMID:17695334

Nersessian, Edward; Silvan, Matthew

2007-07-01

329

Human immunodeficiency virus and acquired immunodeficiency syndrome: correlation but not causation.  

PubMed Central

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 40% of American cases, it has been hypothesized that this virus causes AIDS by killing T cells. Consequently, the virus was termed human immunodeficiency virus (HIV), and antibody to HIV became part of the definition of AIDS. The hypothesis that HIV causes AIDS is examined in terms of Koch's postulates and epidemiological, biochemical, genetic, and evolutionary conditions of viral pathology. HIV does not fulfill Koch's postulates: (i) free virus is not detectable in most cases of AIDS; (ii) virus can only be isolated by reactivating virus in vitro from a few latently infected lymphocytes among millions of uninfected ones; (iii) pure HIV does not cause AIDS upon experimental infection of chimpanzees or accidental infection of healthy humans. Further, HIV violates classical conditions of viral pathology. (i) Epidemiological surveys indicate that the annual incidence of AIDS among antibody-positive persons varies from nearly 0 to over 10%, depending critically on nonviral risk factors. (ii) HIV is expressed in less than or equal to 1 of every 10(4) T cells it supposedly kills in AIDS, whereas about 5% of all T cells are regenerated during the 2 days it takes the virus to infect a cell. (iii) If HIV were the cause of AIDS, it would be the first virus to cause a disease only after the onset of antiviral immunity, as detected by a positive "AIDS test." (iv) AIDS follows the onset of antiviral immunity only after long and unpredictable asymptomatic intervals averaging 8 years, although HIV replicates within 1 to 2 days and induces immunity within 1 to 2 months. (v) HIV supposedly causes AIDS by killing T cells, although retroviruses can only replicate in viable cells. In fact, infected T cells grown in culture continue to divide. (vi) HIV is isogenic with all other retroviruses and does not express a late, AIDS-specific gene. (vii) If HIV were to cause AIDS, it would have a paradoxical, country-specific pathology, causing over 90% Pneumocystis pneumonia and Kaposi sarcoma in the U.S. but over 90% slim disease, fever, and diarrhea in Africa.(viii) It is highly improbable that within the last few years two viruses (HIV-1 and HIV-2) that are only 40% sequence-related would have evolved that could both cause the newly defined syndrome AIDS. Also, viruses are improbable that kill their only natural host with efficiencies of 50-100%, as is claimed for HIVs. It is concluded that HIV is not sufficient for AIDS and that it may not even be necessary for AIDS because its activity is just as low in symptomatic carriers as in asymptomatic carriers. The correlation between antibody to HIV and AIDS does not prove causation, because otherwise indistinguishable diseases are now set apart only on the basis of this antibody. I propose that AIDS is not a contagious syndrome caused by one conventional virus or microbe. No such virus or microbe would require almost a decade to cause primary disease, nor could it cause the diverse collection of AIDS diseases. Neither would its host range be as selective as that of AIDS, nor could it survive if it were as inefficiently transmitted as AIDS. Since AIDS is defined by new combinations of conventional diseases, it may be caused by new combinations of conventional pathogens, including acute viral or microbial infections and chronic drug use and malnutrition. The long and unpredictable intervals between infection with HIV and AIDS would then reflect the thresholds for these pathogenic factors to cause AIDS diseases, instead of an unlikely mechanism of HIV pathogenesis. PMID:2644642

Duesberg, P H

1989-01-01

330

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

331

Genetics Home Reference: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia  

MedlinePLUS

... X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (often shortened to XMEN ) On ... X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (typically known by the acronym ...

332

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

Code of Federal Regulations, 2011 CFR

...information related to infection with the human immunodeficiency virus to public health authorities. 1.486 Section 1.486...information related to infection with the human immunodeficiency virus to public health authorities. (a) In the...

2011-07-01

333

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

Code of Federal Regulations, 2013 CFR

...information related to infection with the human immunodeficiency virus to public health authorities. 1.486 Section 1.486...information related to infection with the human immunodeficiency virus to public health authorities. (a) In the...

2013-07-01

334

Comparison of Acid Neutralizing and Non-Acid Neutralizing Stress Ulcer Prophylasis in Thermally Injured Patients.  

National Technical Information Service (NTIS)

We have compared the effectiveness of non-acid neutralizing stress ulcer prophylaxis (SUC) with sucralfate (n = 48) with that of acid neutralizing prophylaxis (AN) utilizing antacids and cimetidine (n = 48) in the prevention of stress ulcer bleeding and n...

W. G. Cioffi, A. T. McManus, W. F. McManus, B. A. Pruitt, L. W. Rue

1994-01-01

335

Characterizations of neutral lipid fatty acids and cis-9,10-epoxy octadecanoic acid in Pneumocystis carinii carinii.  

PubMed Central

Pneumocystis carinii causes pneumonitis in immunodeficient individuals and is a prevalent opportunistic infection of patients with AIDS. This pathogen resides extracellularly in the hypophase lining the alveolar epithelium, which is highly enriched in lung surfactant lipids. Procedures yielding highly pure organism preparations that enable reliable biochemical analyses of organisms isolated from the lungs of infected laboratory animals have been developed. The results of the present study revealed that the fatty acid profiles of total lipids, the neutral lipid traction, and individual neutral lipid classes of lungs from normal and immunosuppressed rats as well as P. carinii were grossly similar, although some quantitative differences were detected. One qualitative exception found was the detection in P. carinii of the rare fatty acid cis-9,10-epoxy stearic acid, which was not detected in the lipids of rat lungs. The detection of this fatty acid in P. carinii may also have important taxonomic implications. Unlike phospholipids, many of the fatty acids of nonmembrane neutral lipids may be utilized by P. carinii for other cellular functions, such as stored reserves for energy production and precursors for organism-specific membrane lipids. The present study represents the first report of detailed fatty acid analyses of individual neutral lipid classes of this important opportunistic pathogen. PMID:8926076

Kaneshiro, E S; Ellis, J E; Guo, Z; Jayasimhulu, K; Maiorano, J N; Kallam, K A

1996-01-01

336

Mutation of Unique Region of Bruton's Tyrosine Kinase in Immunodeficient XID Mice  

Microsoft Academic Search

The cytoplasmic tyrosine kinase, Bruton's tyrosine kinase (Btk, formerly bpk or atk), is crucial for B cell development. Loss of kinase activity results in the human immunodeficiency, X-linked agammaglobulinemia, characterized by a failure to produce B cells. In the murine X-linked immunodeficiency (XID), B cells are present but respond abnormally to activating signals. The Btk gene, btk, was mapped to

David J. Rawlings; Douglas C. Saffran; Satoshi Tsukada; David A. Largaespada; J. Christopher Grimaldi; Lucie Cohen; Randolph N. Mohr; J. Fernando Bazan; Maureen Howard; Neal G. Copeland; Nancy A. Jenkins; Owen N. Witte

1993-01-01

337

Origin and Biology of Simian Immunodeficiency Virus in Wild-Living Western Gorillas  

Microsoft Academic Search

Western lowland gorillas (Gorilla gorilla gorilla) are infected with a simian immunodeficiency virus (SIVgor) that is closely related to chimpanzee and human immunodeficiency viruses (SIVcpz and HIV-1, respectively) in west central Africa. Although existing data suggest a chimpanzee origin for SIVgor, a paucity of available sequences has precluded definitive conclusions. Here, we report the molecular characterization of one partial (BQ664)

Jun Takehisa; Matthias H. Kraus; Ahidjo Ayouba; Elizabeth Bailes; Fran Van Heuverswyn; Julie M. Decker; Yingying Li; Rebecca S. Rudicell; Gerald H. Learn; Cecile Neel; Eitel Mpoudi Ngole; George M. Shaw; Martine Peeters; Paul M. Sharp; Beatrice H. Hahn

2009-01-01

338

Postnatal transmission of human immunodeficiency virus type 1: The breast-feeding dilemma  

Microsoft Academic Search

Human milk has been considered only recently as a source of transmission for the human immunodeficiency virus. The estimated postnatal transmission rate from mothers who acquired human immunodeficiency virus infection while lactating is 26% (95% confidence interval 13% to 39%) and may be in the range of 8% to 18% from mothers who were infected before becoming pregnant. Risk factors

Philippe Van de Perre

1995-01-01

339

Imunodeficiências primárias: aspectos relevantes para o pneumologista* Primary immunodeficiency diseases: relevant aspects for pulmonologists  

Microsoft Academic Search

Primary immunodeficiency diseases comprise a genetically heterogeneous group of disorders that affect distinct components of the innate and adaptive immune system, such as neutrophils, macrophages, dendritic cells, complement proteins and natural killer cells, as well as T and B lymphocytes. The study of these diseases has provided essential insights into the functioning of the immune system. Primary immunodeficiency diseases have

Pérsio Roxo Júnior

340

Gene therapy of primary T cell immunodeficiencies Alain Fischer 1,2,3  

E-print Network

immunodeficiencies. This has been achieved for 2 forms of SCID, i.e SCID-X1 (c deficiency) and adenosine deaminase, as observed in the SCID- X1 trials has led to replace these vectors by self inactivated (SIN) retro(or lenti studies in SCID as well as in other primary immunodeficiencies, such as the Wiskott Aldrich syndrome

Paris-Sud XI, Université de

341

Rev-Independent Simian Immunodeficiency Virus Strains Are Nonpathogenic in Neonatal Macaques  

Microsoft Academic Search

The viral protein Rev is essential for the export of the subset of unspliced and partially spliced lentiviral mRNAs and the production of structural proteins. Rev and its RNA binding site RRE can be replaced in both human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) by the constitutive RNA transport element CTE of the simian type D retroviruses. We

Agneta S. von Gegerfelt; Vladimir Liska; Pei-Lin Li; Harold M. McClure; Kyoji Horie; Filomena Nappi; David C. Montefiori; George N. Pavlakis; Marta L. Marthas; Ruth M. Ruprecht; Barbara K. Felber

2002-01-01

342

Clinical and immunologic analyses of 103 patients with common variable immunodeficiency  

Microsoft Academic Search

Common variable immunodeficiency (CVI) or hypogammaglobulinemia is a heterogeneous primary immunodeficiency disease in which B cells produce little or no antibody. Since the disease is relatively rare and the spectrum of associated illnesses is broad, patients are given care by a variety of specialists. Thus it has been difficult to determine the incidence of specific complications. In these studies we

C. Cunningham-Rundles

1989-01-01

343

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

344

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

345

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

346

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

347

Experimental Investigation of Neutral-Neutral Reactions and Energy Transfer at Low Temperatures  

Microsoft Academic Search

Over the last few years, we have applied the CRESU (Reaction Kinetics in Uniform Supersonic Flow) technique to the study of neutral-neutral reactions and energy transfer processes in the gas phase. This has enabled the rates of a wide range of reactions between electrically neutral species to be measured down to temperatures as low as ˜ 10 K. These results

Ian R. Sims

2005-01-01

348

Human immunodeficiency virus-associated nephropathy (HIVAN) in Nigerian children  

Microsoft Academic Search

Human immunodeficiency virus-associated nephropathy (HIVAN) has rarely been reported in African children. In this single-center\\u000a study, we analyzed ten children diagnosed with HIVAN from January 2000 to October 2006. There were eight boys and two girls,\\u000a with a male:female ratio of 4:1. Their ages were from 5 months to 15 years (mean 6.8?±?6.2 years), with a peak age of 5–9 years.\\u000a The presenting complaints

Ifeoma C. Anochie; Felicia U. Eke; Augustina N. Okpere

2008-01-01

349

Beware the lymphopenia: a case of severe combined immunodeficiency.  

PubMed

We present a case of a 2-month-old boy with partially treated meningitis and suspected Pneumocystis carinii pneumonia. A full blood count revealed profound lymphopenia. The child was diagnosed with adenosine deaminase deficiency, a rare cause of severe combined immunodeficiency (SCID). SCID is an immunological emergency and must be considered in any lymphopaenic infant with opportunistic infection. We discuss adenosine deaminase-deficient SCID, which can involve multiple systems and in which other treatment options apart from bone marrow transplant are available. PMID:21843190

Mehr, Sam; Kakakios, Alyson; Shaw, Peter; Webster, Richard; Kemp, Andrew

2011-08-01

350

Cutaneous cytomegalovirus infection in a patient with acquired immunodeficiency syndrome.  

PubMed

Abstract Cytomegalovirus (CMV) infection in immunocompromised patients is a common opportunistic systemic infection which can lead to death, and usually presents with visceral manifestations, especially of the lung, brain, eye, and gastrointestinal tract. Cutaneous CMV infection is, however, relatively rare in immunocompromised patients. Cutaneous CMV infection can have variable clinical and histologic manifestations, and thus can be easily missed. We report a case of cutaneous CMV infection in a patient with acquired immunodeficiency syndrome, presenting as a generalized, pruritic, erythematous, maculopapular eruption. PMID:18937659

AbdullGaffar, Badr; Raman, Lakshmiah G; Al Muala, Alia

2008-09-01

351

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

352

Vaccine-acquired rotavirus in infants with severe combined immunodeficiency.  

PubMed

Live pentavalent human-bovine reassortant rotavirus vaccine is recommended in the United States for routine immunization of infants. We describe three infants, two with failure to thrive, who had dehydration and diarrhea within 1 month after their first or second rotavirus immunization and subsequently received a diagnosis of severe combined immunodeficiency. Rotavirus was detected, by means of reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, in stool specimens obtained from all three infants, and gene-sequence analysis revealed the presence of vaccine rotavirus. These infections raise concerns regarding the safety of rotavirus vaccine in severely immunocompromised patients. PMID:20107217

Patel, Niraj C; Hertel, Paula M; Estes, Mary K; de la Morena, Maite; Petru, Ann M; Noroski, Lenora M; Revell, Paula A; Hanson, I Celine; Paul, Mary E; Rosenblatt, Howard M; Abramson, Stuart L

2010-01-28

353

Update on Human Immunodeficiency Virus (HIV)-2 Infection  

PubMed Central

Infection with human immunodeficiency virus type 2 (HIV-2) occurs mainly in West Africa, but an increasing number of cases have been recognized in Europe, India, and the United States. In this era of global integration, clinicians must be aware of when to consider the diagnosis of HIV-2 infection and how to test for this virus. Although there is debate regarding when therapy should be initiated and which regimen should be chosen, recent trials have provided important information on treatment options for HIV-2 infection. In this review, we present information on recent clinical advances in our understanding of HIV-2 infection and highlight remaining diagnostic and therapeutic challenges. PMID:21367732

Campbell-Yesufu, Omobolaji T.

2011-01-01

354

Autism in a child with common variable immunodeficiency.  

PubMed

Autism is a neurodevelopmental disorder, characterized by poor social interaction and communication impairment and repetitive behavior. Autism is considered as a genetic and multifactorial disorder, with diverse risk factors involved.Herein, we report a 13-year-old male with common variable immunodeficiency (CVID), who was diagnosed with autism at the age of 3 years old. As there are some evidences about the role of the immune system defects in the pathogenesis of autism, specific primary antibody deficiency diseases such as CVID might predispose some affected cases to such neurodevelopmental disorders. PMID:23893814

Salehi Sadaghiani, Mohammad; Aghamohammadi, Asghar; Ashrafi, Mahmoud-Reza; Hosseini, Firozeh; Abolhassani, Hassan; Rezaei, Nima

2013-09-01

355

[Granulomatous lymphocytic interstitial lung disease in common variable immunodeficiency].  

PubMed

Common variable immunodeficiency (CVID) is the most frequent primary immune deficiency. Recurrent infections are classical consequences of CVID, but their impact has been largely reduced by immunoglobulin replacement. CVID is also associated with various inflammatory and autoimmune manifestations resulting from abnormal cellular immunity. The lungs are especially affected by a recently described entity called granulomatous lymphocytic interstitial lung disease (GLILD). GLILD currently constitutes an important cause of morbidity and mortality in these patients. It is distinct from bronchiectasis secondary to recurrent infections, and presents similarities but also striking differences with sarcoidosis. PMID:24354253

Bianchi, M Prella; Letovanec, I; Spertini, F; Nicod, L P; Lazor, R

2013-11-20

356

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

357

Towards detecting the human immunodeficiency virus using microcantilever sensors  

NASA Astrophysics Data System (ADS)

Detecting the human immunodeficiency virus (HIV) is difficult because the virus is prone to mutations and is in low concentrations in the body. Inside the HIV virion are two well characterized single stranded (ss) RNA molecules (viral genome) that feature both variable regions and regions that are conserved under virus mutation. In this work, microcantilever sensors have been employed as potential HIV detectors by targeting a conserved sequence of the viral genome by attempting to detect target ssDNA and ssRNA molecules that are significantly longer than the ssDNA molecules functionalized on the cantilever.

Alodhayb, Abdullah; Brown, Nicole; Saydur Rahman, S. M.; Harrigan, Richard; Beaulieu, L. Y.

2013-04-01

358

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

359

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

360

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

361

Implications of Internet architecture on net neutrality  

Microsoft Academic Search

Net neutrality represents the idea that Internet users are entitled to service that does not discriminate on the basis of source, destination, or ownership of Internet traffic. The United States Congress is considering legislation on net neutrality, and debate over the issue has generated intense lobbying. Congressional action will substantially affect the evolution of the Internet and of future Internet

Scott Jordan

2009-01-01

362

Reconciling niche and neutrality: the continuum hypothesis  

E-print Network

LETTER Reconciling niche and neutrality: the continuum hypothesis Dominique Gravel,1 * Charles D, NY 12545, USA *Correspondence: E-mail: domgravl@globetrotter.net Abstract In this study, we ask if instead of being fundamentally opposed, niche and neutral theories could simply be located at the extremes

363

A Technical Approach to Net Neutrality  

Microsoft Academic Search

A recent statement by AT&T CEO Ed Whitacre sparked considerable fear in the public that the Internet may not be open any more: the ISPs dictate which sites\\/applications flourish and which flounder. The state- ment triggered the heated debate on net neutrality and ignited the battle to enact net neutrality legislation. How - ever, by the date of writing, all

Xiaowei Yang; Gene Tsudik; Xin Liu

2006-01-01

364

Neutralization of wastewater from nitrite passivation  

SciTech Connect

A method for neutralization of wastewater formed in nitrite passivation has been presented. The method consists of introducing urea into wastewater and acidifying it with sulphuric acid. Wastewater is neutralized with lime. After clarification, wastewater can be drained outside the plant.

Pawlowski, L.; Mientki, B.; Wasag, H.

1982-01-01

365

A New Age of Constructivism: "Mode Neutral"  

ERIC Educational Resources Information Center

This article presents work in progress exploring social constructivism within Mode Neutral, and how various conditions impact upon the student experience. Mode Neutral's three dimensions--curriculum design, the role of the tutor and communication for learning--are affected by the conditions that can vary in any given context. The authors realise…

Reed, Peter; Smith, Brian; Sherratt, Cathy

2008-01-01

366

PERSPECTIVES Sampling Hubbell's neutral theory of biodiversity  

E-print Network

IDEAS AND PERSPECTIVES Sampling Hubbell's neutral theory of biodiversity David Alonso1,2 * and Alan. Here, instead of taking a multivariate approach, we further develop the sampling theory of Hubbell. Keywords Abundance distributions, Hubbell's neutral theory, Poissonian zero-sum multinomial, sampling

McKane, Alan

367

Targets for high power neutral beams  

SciTech Connect

Stopping high-power, long-pulse beams is fast becoming an engineering challenge, particularly in neutral beam injectors for heating magnetically confined plasmas. A brief review of neutral beam target technology is presented along with heat transfer calculations for some selected target designs.

Kim, J.

1980-01-01

368

Using Neutralizing Routines To Reduce Problem Behaviors.  

ERIC Educational Resources Information Center

A study examined the relationship between neutralizing routines and problem behavior in three adolescents with severe intellectual disabilities. Functional analyses found the problem behaviors were motivated by either escape or tangible items. Results found that neutralizing routines were effective in reducing self-injurious behavior and…

Horner, Robert H.; Day, H. Michael; Day, Julie R.

1997-01-01

369

Gender Neutrality: Women's Friend or Foe?  

ERIC Educational Resources Information Center

Gender neutral public policies are those that are either silent on the question of the existence of significant gender differences or incorporate a perspective which mandates that such differences be ignored. Prominent voices today contend that gender neutrality favors males and have held the male standard as the one for which women should aspire.…

Steuernagel, Trudy

370

Recent developments in neutral beam processes  

Microsoft Academic Search

It is my great pleasure to introduce this special cluster issue of Journal of Physics D: Applied Physics, devoted to recent developments in neutral beam processes. It is an even greater pleasure to behold the enormous progress in this area over the last five years. Research on neutral beam processes has advanced due to the development of new nano-device technologies.

Seiji Samakawa

2008-01-01

371

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

372

Sphingolipid metabolism and neutral sphingomyelinases  

PubMed Central

Sphingolipids are an important class of lipid molecules that play fundamental roles in our cells and body. Beyond a structural role, it is now clearly established that sphingolipids serve as bioactive signaling molecules to regulate diverse processes including inflammatory signaling, cell death, proliferation, and pain sensing. Sphingolipid metabolites have been implicated in the onset and progression of various diseases including cancer, lung disease, diabetes, and lysosomal storage disorders. Here we will review sphingolipid metabolism to introduce basic concepts as well as emerging complexities in sphingolipid function gained from modern technological advances and detailed cell and animal studies. Furthermore, we will discuss the family of neutral sphingomyelinases (N-SMases), which generate ceramide through the hydrolysis of sphingomyelin and are key enzymes in sphingolipid metabolism. Four mammalian N-SMase enzymes have now been identified. Most prominent is nSMase2 with established roles in bone mineralization, exosome formation, and cellular stress responses. Function for the other N-SMases have been more enigmatic and is an area of active investigation. The known properties and potential role(s) of each enzyme will be discussed to help guide to future studies. PMID:23579449

Airola, Michael V.; Hannun, Yusuf A.

2014-01-01

373

THE ECONOMIC BURDEN OF ILLNESS FOR HOUSEHOLDS IN DEVELOPING COUNTRIES: A REVIEW OF STUDIES FOCUSING ON MALARIA, TUBERCULOSIS, AND HUMAN IMMUNODEFICIENCY VIRUS\\/ACQUIRED IMMUNODEFICIENCY SYNDROME  

Microsoft Academic Search

Ill-health contributes to impoverishment, a process brought into sharper focus by the impact of the human immunodeficiency virus\\/acquired immunodeficiency syndrome (HIV\\/AIDS) epidemic. This paper reviews studies that have measured the economic costs and consequences of illness for households, focusing on malaria, tuberculosis (TB), and HIV\\/AIDS. It finds that in resource-poor settings illness imposed high and regressive cost burdens on patients

STEVEN RUSSELL

374

An Orphan Seven-Transmembrane Domain Receptor Expressed Widely in the Brain Functions as a Coreceptor for Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus  

Microsoft Academic Search

Both CD4 and an appropriate coreceptor are necessary for infection of cells by human immunodeficiency virus type 1 (HIV-1) and most strains of HIV-2. The chemokine receptors CCR5 and CXCR4 are the major HIV-1 coreceptors, although some virus strains can also utilize alternative coreceptors such as CCR3 to infect cells. In contrast, most if not all simian immunodeficiency virus (SIV)

AIMEE L. EDINGER; TREVOR L. HOFFMAN; MATTHEW SHARRON; BENHUR LEE; YANJI YI; WONKYU CHOE; DENNIS L. KOLSON; BRANKA MITROVIC; YIQING ZHOU; DARYL FAULDS; RONALD G. COLLMAN; JOSEPH HESSELGESSER; RICHARD HORUK; ROBERT W. DOMS

1998-01-01

375

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

376

Primary Immunodeficiency Diseases: An Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency  

PubMed Central

We report the updated classification of primary immunodeficiencies (PIDs) compiled by the Expert Committee of the International Union of Immunological Societies. In comparison to the previous version, more than 30 new gene defects are reported in this updated version. In addition, we have added a table of acquired defects that are phenocopies of PIDs. For each disorder, the key clinical and laboratory features are provided. This classification is the most up-to-date catalog of all known PIDs and acts as a current reference of the knowledge of these conditions and is an important aid for the molecular diagnosis of patients with these rare diseases. PMID:24795713

Al-Herz, Waleed; Bousfiha, Aziz; Casanova, Jean-Laurent; Chatila, Talal; Conley, Mary Ellen; Cunningham-Rundles, Charlotte; Etzioni, Amos; Franco, Jose Luis; Gaspar, H. Bobby; Holland, Steven M.; Klein, Christoph; Nonoyama, Shigeaki; Ochs, Hans D.; Oksenhendler, Erik; Picard, Capucine; Puck, Jennifer M.; Sullivan, Kate; Tang, Mimi L. K.

2014-01-01

377

Evaluating the immunogenicity of a disulfide-stabilized, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1.  

PubMed

The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) complex comprises three gp120 exterior glycoproteins each noncovalently linked to a gp41 transmembrane glycoprotein. Monomeric gp120 proteins can elicit antibodies capable of neutralizing atypically sensitive test viruses in vitro, but these antibodies are ineffective against representative primary isolates and the gp120 vaccines failed to provide protection against HIV-1 transmission in vivo. Alternative approaches to raising neutralizing antibodies are therefore being pursued. Here we report on the antibody responses generated in rabbits against a soluble, cleaved, trimeric form of HIV-1(JR-FL) Env. In this construct, the gp120 and gp41 moieties are covalently linked by an intermolecular disulfide bond (SOS gp140), and an I559P substitution has been added to stabilize gp41-gp41 interactions (SOSIP gp140). We investigated the value of DNA priming and compared the use of membrane-bound and soluble priming antigens and of repeat boosting with soluble and particulate protein antigen. Compared to monomeric gp120, SOSIP gp140 trimers elicited approximately threefold lower titers of anti-gp120 antibodies. Priming with DNA encoding a membrane-bound form of the SOS gp140 protein, followed by several immunizations with soluble SOSIP gp140 trimers, resulted in antibodies capable of neutralizing sensitive strains at high titers. A subset of these sera also neutralized, at lower titers, HIV-1(JR-FL) and some other primary isolates in pseudovirus and/or whole-virus assays. Neutralization of these viruses was immunoglobulin mediated and was predominantly caused by antibodies to gp120 epitopes, but not the V3 region. PMID:15994775

Beddows, Simon; Schülke, Norbert; Kirschner, Marc; Barnes, Kelly; Franti, Michael; Michael, Elizabeth; Ketas, Thomas; Sanders, Rogier W; Maddon, Paul J; Olson, William C; Moore, John P

2005-07-01

378

Evaluating the Immunogenicity of a Disulfide-Stabilized, Cleaved, Trimeric Form of the Envelope Glycoprotein Complex of Human Immunodeficiency Virus Type 1  

PubMed Central

The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) complex comprises three gp120 exterior glycoproteins each noncovalently linked to a gp41 transmembrane glycoprotein. Monomeric gp120 proteins can elicit antibodies capable of neutralizing atypically sensitive test viruses in vitro, but these antibodies are ineffective against representative primary isolates and the gp120 vaccines failed to provide protection against HIV-1 transmission in vivo. Alternative approaches to raising neutralizing antibodies are therefore being pursued. Here we report on the antibody responses generated in rabbits against a soluble, cleaved, trimeric form of HIV-1JR-FL Env. In this construct, the gp120 and gp41 moieties are covalently linked by an intermolecular disulfide bond (SOS gp140), and an I559P substitution has been added to stabilize gp41-gp41 interactions (SOSIP gp140). We investigated the value of DNA priming and compared the use of membrane-bound and soluble priming antigens and of repeat boosting with soluble and particulate protein antigen. Compared to monomeric gp120, SOSIP gp140 trimers elicited approximately threefold lower titers of anti-gp120 antibodies. Priming with DNA encoding a membrane-bound form of the SOS gp140 protein, followed by several immunizations with soluble SOSIP gp140 trimers, resulted in antibodies capable of neutralizing sensitive strains at high titers. A subset of these sera also neutralized, at lower titers, HIV-1JR-FL and some other primary isolates in pseudovirus and/or whole-virus assays. Neutralization of these viruses was immunoglobulin mediated and was predominantly caused by antibodies to gp120 epitopes, but not the V3 region. PMID:15994775

Beddows, Simon; Schülke, Norbert; Kirschner, Marc; Barnes, Kelly; Franti, Michael; Michael, Elizabeth; Ketas, Thomas; Sanders, Rogier W.; Maddon, Paul J.; Olson, William C.; Moore, John P.

2005-01-01

379

When less is more: primary immunodeficiency with an autoinflammatory kick  

PubMed Central

Purpose of review Next-generation sequencing is revolutionizing the molecular taxonomy of human disease. Recent studies of patients with unexplained autoinflammatory disorders reveal germline genetic mutations that target important regulators of innate immunity. Recent findings Whole-exome analyses of previously undiagnosed patients have catalyzed the recognition of two new disease genes. First, a phenotypic spectrum, including livedo racemosa, fever with early-onset stroke, polyarteritis nodosa, and Sneddon syndrome, is caused by loss-of-function mutations in cat eye syndrome chromosome region, candidate 1 (CECR1), encoding adenosine deaminase 2. Adenosine deaminase 2 is a secreted protein expressed primarily in myeloid cells, and a regulator of macrophage differentiation and endothelial development. Disease-associated mutations impair anti-inflammatory M2 macrophage differentiation. Second, patients presenting with cold-induced urticaria, granulomatous rash, autoantibodies, and common variable immunodeficiency, or with blistering skin lesions, bronchiolitis, enterocolitis, ocular inflammation, and mild immunodeficiency harbor distinct mutations in phospholipase C?2, encoding a signaling molecule expressed in natural killer cells, mast cells, and B lymphocytes. These mutations inhibit the function of a phospholipase C?2 autoinhibitory domain, causing increased or constitutive signaling. Summary These findings underscore the power of next-generation sequencing, demonstrating how the primary deficiency of key molecular regulators or even regulatory motifs may lead to autoinflammation, and suggesting a possible role for cat eye syndrome chromosome region, candidate 1 and phospholipase C?2 in common diseases. PMID:25337682

Giannelou, Angeliki; Zhou, Qing; Kastner, Daniel L.

2014-01-01

380

Common variable immunodeficiency: clinical and immunological features of 248 patients.  

PubMed

Common variable immunodeficiency (CVI) is a primary immunodeficiency disease characterized by reduced serum immunoglobulins and heterogeneous clinical features. In these studies we describe the clinical and immunological status of 248 consecutively referred CVI patients of age range 3-79 years who have been followed for a period of 1-25 years. The median age at the time of onset of symptoms was 23 years for males and 28 years for females; the mean age at which the diagnosis of CVI was made was 29 years for males and 33 years for females. Forty percent of patients had impaired T cell proliferation to one or more mitogens; lymphocyte transformation to mitogens was directly related to the level of the serum IgG. Females at all ages had higher levels of serum IgM than males. Survival 20 years after diagnosis of CVI was 64% for males and 67% for females, compared to the expected 92% population survival for males and 94% for females. Parameters associated with mortality in this period were lower levels of serum IgG, poorer T cell responses to phytohemagglutinin, and, particularly, a lower percentage of peripheral B cells (P < 0.006). PMID:10413651

Cunningham-Rundles, C; Bodian, C

1999-07-01

381

The genetic basis of severe combined immunodeficiency and its variants  

PubMed Central

Severe combined immunodeficiency (SCID) syndromes are characterized by a block in T lymphocyte differentiation that is variably associated with abnormal development of other lymphocyte lineages (B and/or natural killer [NK] cells), leading to death early in life unless treated urgently by hematopoietic stem cell transplant. SCID comprises genotypically and phenotypically heterogeneous conditions, of which the genetic basis for approximately 85% of the underlying immunologic defects have been recently elucidated. A major obstacle in deciphering the pathogenesis of SCID syndromes is that different mutations in a single gene may give rise to distinct clinical conditions and that a similar clinical phenotype can result from mutations in different genes. Mutation analysis is now an important component of the complete evaluation of a patient with SCID since it has a dramatic impact on many aspects of this potentially life-threatening disease such as genetic counseling, prenatal diagnosis, modalities of treatment, and, eventually, prognosis. Dr Robert Good, one of the founders of modern immunology, described the SCID syndrome as “experiments of nature.” By understanding the cellular and genetic basis of these immunodeficiency diseases and, eventually, normal immunity, we optimize the “bedside to research laboratory and back again” approach to medicine. PMID:23776382

Tasher, Diana; Dalal, Ilan

2012-01-01

382

Do ribosomopathies explain some cases of common variable immunodeficiency?  

PubMed Central

The considerable clinical heterogeneity of patients with common variable immunodeficiency disorders (CVID) shares some similarity with bone-marrow failure disorders such as Diamond–Blackfan anaemia (DBA) and Shwachman–Diamond syndrome (SDS), now recognized as defects in ribosome biogenesis or ribosomopathies. The recognition of a patient with DBA who subsequently developed CVID lends support to our previous finding of a heterozygous mutation in the SBDS gene of SBDS in another CVID patient, suggesting that ribosome biogenesis defects are responsible for a subset of CVID. Genetic defects in the ribosomal translational machinery responsible for various bone marrow failure syndromes are recognized readily when they manifest in children, but diagnosing these in adults presenting with complex phenotypes and hypogammaglobulinaemia can be a challenge. In this perspective paper, we discuss our clinical experience in CVID patients with ribosomopathies, and review the immunological abnormalities in other conditions associated with ribosomal dysfunction. With genetic testing available for various bone marrow failure syndromes, our hypothesis that ribosomal abnormalities may be present in patients with CVID could be proved in future studies by testing for mutations in specific ribosomal genes. New knowledge might then be translated into novel therapeutic strategies for patients in this group of immunodeficiency disorders. PMID:21062271

Khan, S; Pereira, J; Darbyshire, P J; Holding, S; Dore, P C; Sewell, W A C; Huissoon, A

2011-01-01

383

Cernunnos/XLF Deficiency: A Syndromic Primary Immunodeficiency.  

PubMed

Artemis, DNA ligase IV, DNA protein kinase catalytic subunit, and Cernunnos/XLF genes in nonhomologous end joining pathways of DNA repair mechanisms have been identified as responsible for radiosensitive SCID. Here, we present a 3-year-old girl patient with severe growth retardation, bird-like face, recurrent perianal abscess, pancytopenia, and polydactyly. Firstly, she was thought as Fanconi anemia and spontaneous DNA breaks were seen on chromosomal analysis. After that DEB test was found to be normal and Fanconi anemia was excluded. Because of that she had low IgG and IgA levels, normal IgM level, and absence of B cells in peripheral blood; she was considered as primary immunodeficiency, Nijmegen breakage syndrome. A mutation in NBS1 gene was not found; then Cernunnos/XLF deficiency was investigated due to clinical similarities with previously reported cases. Homozygous mutation in Cernunnos/XLF gene (NHEJ1) was identified. She is now on regular IVIG prophylaxis and has no new infection. Fully matched donor screening is in progress for bone marrow transplantation which is curative treatment of the disease. In conclusion, the patients with microcephaly, bird-like face, and severe growth retardation should be evaluated for hypogammaglobulinemia and primary immunodeficiency diseases. PMID:24511403

Cipe, Funda Erol; Aydogmus, Cigdem; Babayigit Hocaoglu, Arzu; Kilic, Merve; Kaya, Gul Demet; Yilmaz Gulec, Elif

2014-01-01

384

Adrenal adenomatoid tumor in a patient with human immunodeficiency virus  

PubMed Central

We present the clinical course of a patient with human immunodeficiency virus and an adrenal adenomatoid tumor (AAT). We describe the clinical course and laboratory, radiographic, and microscopic findings of a patient with human immunodeficiency virus (HIV) and an adenomatoid tumor of the right adrenal gland. A review of the literature was also done via electronic searches through PubMed for articles from 1965 to 2008 that contained the following search terms, adenomatoid tumor limited to the English language only. A 22 year-old African-American male with HIV was incidentally found to have a hypermetabolic right adrenal mass. The patient underwent laparoscopic adrenalectomy and the mass had morphological and immunohistochemical features that were consistent with an AAT. A review of the medical literature reveals that almost all cases of AAT were in male patients (96%) with a mean age of 41±11 years (range=22–64) with no significant difference in laterality (right side=46%, left side=50%, unknown=4%). AAT have an average size of 4.2±3.5 cm (range=0.5–14.3 cm). Pre-operative imaging studies do not appear to be able to reliably distinguish AAT from other types of adrenocortical tumors. For reasons that require further research, AAT typically occur in male patients and may be associated with immunosuppression. AAT can be safely removed laparoscopically with no evidence of long-term recurrence even with tumor extension beyond the adrenal capsule. PMID:21769320

Phitayakorn, Roy; MacLennan, Gregory; Sadow, Peter; Wilhelm, Scott

2011-01-01

385

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

386

Oral lesions: A true clinical indicator in human immunodeficiency virus.  

PubMed

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

2011-07-01

387

Cernunnos/XLF Deficiency: A Syndromic Primary Immunodeficiency  

PubMed Central

Artemis, DNA ligase IV, DNA protein kinase catalytic subunit, and Cernunnos/XLF genes in nonhomologous end joining pathways of DNA repair mechanisms have been identified as responsible for radiosensitive SCID. Here, we present a 3-year-old girl patient with severe growth retardation, bird-like face, recurrent perianal abscess, pancytopenia, and polydactyly. Firstly, she was thought as Fanconi anemia and spontaneous DNA breaks were seen on chromosomal analysis. After that DEB test was found to be normal and Fanconi anemia was excluded. Because of that she had low IgG and IgA levels, normal IgM level, and absence of B cells in peripheral blood; she was considered as primary immunodeficiency, Nijmegen breakage syndrome. A mutation in NBS1 gene was not found; then Cernunnos/XLF deficiency was investigated due to clinical similarities with previously reported cases. Homozygous mutation in Cernunnos/XLF gene (NHEJ1) was identified. She is now on regular IVIG prophylaxis and has no new infection. Fully matched donor screening is in progress for bone marrow transplantation which is curative treatment of the disease. In conclusion, the patients with microcephaly, bird-like face, and severe growth retardation should be evaluated for hypogammaglobulinemia and primary immunodeficiency diseases. PMID:24511403

Cipe, Funda Erol; Aydogmus, Cigdem; Babayigit Hocaoglu, Arzu; Kilic, Merve; Kaya, Gul Demet; Yilmaz Gulec, Elif

2014-01-01

388

Neurobiology of simian and feline immunodeficiency virus infections.  

PubMed

Experimental and clinical evidence indicates that all lentiviruses of animals and humans are neurotropic and potentially neurovirulent. The prototypic animal lentiviruses, visna virus in sheep and caprine arthritis encephalitis virus in goats have been known for decades to induce neurologic disease. More recently, infection of the brain with the human immunodeficiency virus (HIV) has been linked to an associated encephalopathy and cognitive/motor complex. While the visna virus and caprine arthritis encephalitis virus are important models of neurologic disease they are not optimal for the study of HIV encephalitis because immune deficiency is only a minor component of the disease they induce. By contrast, the recently isolated lentiviruses from monkeys and cats, the simian and feline immunodeficiency viruses (SIV and FIV respectively), are profoundly immunosuppressive as well as neurotropic. SIV infection of the central nervous system of macaques now provides the best animal model for HIV infection of the human brain due to the close evolutionary relationship between monkeys and man, the genetic relatedness of their respective lentiviruses, and the similarities in the neuropathology. This chapter will compare and contrast the neurobiology of SIV and FIV with HIV. PMID:1669709

Lackner, A A; Dandekar, S; Gardner, M B

1991-04-01

389

Low human immunodeficiency virus envelope diversity correlates with low in vitro replication capacity and predicts spontaneous control of plasma viremia after treatment interruptions.  

PubMed

Genetic diversity of viral isolates in human immunodeficiency virus (HIV)-infected individuals varies substantially. However, it remains unclear whether HIV-related disease progresses more rapidly in patients harboring virus swarms with low or high diversity and, in the same context, whether high or low diversity is required to induce potent humoral and cellular immune responses. To explore whether viral diversity predicts virologic control, we studied HIV-infected patients who received antiretroviral therapy (ART) for years before undergoing structured treatment interruptions (STI). Viral diversity before initiation of ART and the ability of the patients to contain viremia after STI and final cessation of treatment was evaluated. Seven out of 21 patients contained plasma viremia at low levels after the final treatment cessation. Clonal sequences encompassing the envelope C2V3C3 domain derived from plasma prior to treatment, exhibited significantly lower diversity in these patients compared to those derived from patients with poor control of viremia. Viral diversity pre-ART correlated with the viral replication capacity of rebounding virus isolates during STI. Neutralizing antibody activity against autologous virus was significantly higher in patients who controlled viremia and was associated with lower pretreatment diversity. No such association was found with binding antibodies directed to gp120. In summary, lower pretreatment viral diversity was associated with spontaneous control of viremia, reduced viral replication capacity and higher neutralizing antibody titers, suggesting a link between viral diversity, replication capacity, and neutralizing antibody activity. PMID:15994796

Joos, Beda; Trkola, Alexandra; Fischer, Marek; Kuster, Herbert; Rusert, Peter; Leemann, Christine; Böni, Jürg; Oxenius, Annette; Price, David A; Phillips, Rodney E; Wong, Joseph K; Hirschel, Bernard; Weber, Rainer; Günthard, Huldrych F

2005-07-01

390

Ascertaining the Reality of Network Neutrality Violation in Backbone ISPs  

E-print Network

Mao Ming Zhang #12;Net neutrality debate 2 #12;What is net neutrality? Network neutrality is a network of government regulation 4 #12;Are there net neutrality violations? Known incidents in broadband networks Telus wider impact 5 #12;What is NVLens (Net neutrality Violation Lens)? First system that detects net

Zhang, Ming

391

30 years of weak neutral currents  

NASA Astrophysics Data System (ADS)

We trace the early history of Neutral and Charged Weak Current studies from the 1930's to the discovery of the W and Z in 1983. The period from approximately 1963 to 1983 saw a great advance in our knowledge of Weak Neutral Currents; the first search for Flavor Changing Weak Neutral Currents (FCNC) in 1963, the discovery of Weak Neutral Currents (WNC) in 1973, as well as the rise of the Standard Model (1974-1978) and the discovery of the (W,Z) in 1983! This report follows an International Symposium on 30 Years of Neutral Currents from Weak Neutral Currents to the (W)/Z and Beyond held in Santa Monica, California, on February 3-5, 1993. Neutral Currents (NC) are important in Supernova explosions and the Early Universe. Recently, the bold speculation has been made that NC can give rise to the chirality of life (DNA). We briefly discuss the pro's and con's of this idea and present some recent simulation results.

Cline, David B.

1994-06-01

392

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

393

Induction of AIDS in Rhesus Monkeys by a Recombinant Simian Immunodeficiency Virus Expressing nef of Human Immunodeficiency Virus Type 1  

PubMed Central

A nef gene is present in all primate lentiviruses, including human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus of macaque monkeys (SIVmac). However, the nef genes of HIV-1 and SIVmac exhibit minimal sequence identity, and not all properties are shared by the two. Nef sequences of SIVmac239 were replaced by four independent nef alleles of HIV-1 in a context that was optimal for expression. The sources of the HIV-1 nef sequences included NL 4-3, a variant NL 4-3 gene derived from a recombinant-infected rhesus monkey, a patient nef allele, and a nef consensus sequence. Of 16 rhesus monkeys infected with these SHIVnef chimeras, 9 maintained high viral loads for prolonged periods, as observed with the parental SIVmac239, and 6 have died with AIDS 52 to 110 weeks postinfection. Persistent high loads were observed at similar frequencies with the four different SIV recombinants that expressed these independent HIV-1 nef alleles. Infection with other recombinant SHIVnef constructions resulted in sequence changes in infected monkeys that either created an open nef reading frame or optimized the HIV-1 nef translational context. The HIV-1 nef gene was uniformly retained in all SHIVnef-infected monkeys. These results demonstrate that HIV-1 nef can substitute for SIVmac nef in vivo to produce a pathogenic infection. However, the model suffers from an inability to consistently obtain persisting high viral loads in 100% of the infected animals, as is observed with the parental SIVmac239. PMID:10364333

Alexander, Louis; Du, Zhenjian; Howe, Anita Y. M.; Czajak, Susan; Desrosiers, Ronald C.

1999-01-01

394

Neutral Supersymmetric Higgs Boson Searches  

SciTech Connect

In some Supersymmetric extensions of the Standard Model, including the Minimal Supersymmetric Standard Model (MSSM), the coupling of Higgs bosons to b-quarks is enhanced. This enhancement makes the associated production of the Higgs with b-quarks an interesting search channel for the Higgs and Supersymmetry at D0. The identification of b-quarks, both online and offline, is essential to this search effort. This thesis describes the author's involvement in the development of both types of b-tagging and in the application of these techniques to the MSSM Higgs search. Work was carried out on the Level-3 trigger b-tagging algorithms. The impact parameter (IP) b-tagger was retuned and the effects of increased instantaneous luminosity on the tagger were studied. An extension of the IP-tagger to use the z-tracking information was developed. A new b-tagger using secondary vertices was developed and commissioned. A tool was developed to allow the use of large multi-run samples for trigger studies involving b-quarks. Offline, a neural network (NN) b-tagger was trained combining the existing offline lifetime based b-tagging tools. The efficiency and fake rate of the NN b-tagger were measured in data and MC. This b-tagger was internally reviewed and certified by the Collaboration and now provides the official b-tagging for all analyses using the Run IIa dataset at D0. A search was performed for neutral MSSM Higgs bosons decaying to a b{bar b} pair and produced in association with one or more b-quarks. Limits are set on the cross-section times the branching ratio for such a process. The limits were interpreted in various MSSM scenarios. This analysis uses the NN b-tagger and was the first to use this tool. The analysis also relies on triggers using the Level-3 IP b-tagging tool described previously. A likelihood discriminant was used to improve the analysis and a neural network was developed to cross-check this technique. The result of the analysis has been submitted to PRL and is comparable to the result from CDF in the same channel which uses approximately twice the integrated luminosity.

Robinson, Stephen Luke; /Imperial Coll., London

2009-09-01

395

Diagnosis and treatment of gastrointestinal disorders in patients with primary immunodeficiency.  

PubMed

Gastrointestinal disorders such as chronic or acute diarrhea, malabsorption, abdominal pain, and inflammatory bowel diseases can indicate immune deficiency. The gastrointestinal tract is the largest lymphoid organ in the body, so it is not surprising that intestinal diseases are common among immunodeficient patients. Gastroenterologists therefore must be able to diagnose and treat patients with primary immunodeficiency. Immune-related gastrointestinal diseases can be classified as those that develop primarily via autoimmunity, infection, an inflammatory response, or malignancy. Immunodeficient and immunocompetent patients with gastrointestinal diseases present with similar symptoms. However, intestinal biopsy specimens from immunodeficient patients often have distinct histologic features, and these patients often fail to respond to conventional therapies. Therefore, early recognition of symptoms and referral to an immunologist for a basic immune evaluation is required to select appropriate treatments. Therapies for primary immunodeficiency comprise immunoglobulin replacement, antibiotics, and, in severe cases, bone marrow transplantation. Treatment of immunodeficient patients with concomitant gastrointestinal disease can be challenging, and therapy with immunomodulators often is required for severe disease. This review aims to guide gastroenterologists in the diagnosis and treatment of patients with primary immunodeficiency. PMID:23501398

Agarwal, Shradha; Mayer, Lloyd

2013-09-01

396

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

397

The Value of Network Neutrality for the Internet of Tomorrow  

E-print Network

...............................................................32 NET NEUTRALITY FROM A PUBLIC SPHERE PERSPECTIVE ....................................................................................................................................44 NET NEUTRALITY: ENDING NETWORK DISCRIMINATION IN EUROPE .The Value of Network Neutrality for the Internet of Tomorrow #12;#12;Edited by Luca Belli

Paris-Sud XI, Université de

398

Generation of donor-specific anti-human leukocyte antigen antibodies after the transplantation of a fully matched kidney allograft and its impact on the selection of a subsequent renal regraft: a case report.  

PubMed

Detection of anti-human leukocyte antigen (HLA) antibodies and identification of their specificities represent important tasks for patients awaiting kidney allografts. Regarding patients immunized by pregnancies, transfusions, or previous transplantations of solid organs, the immunization status must be observed carefully because grafting them with HLA phenotypes recognized by their antibodies represents the main cause for hyper-acute or acute rejection episodes, often leading to transplant loss. A 10-year-old patient with end-stage renal insufficiency of HLA type A3, 25; B8, 18, (Bw6); Cw7,12; DR15,17; DR51,52; DQ2,6 received a deceased donor graft showing no HLA mismatch in 1998. It lost function after 8 years, resulting in the patient's re-entry onto the waiting list for kidney transplantation in 2006. Antibody screening detected anti-HLA-A25, A26, A34, and A66 (broad A10) antibodies using various techniques (DynaChip, Single Antigen enzyme-linked immunosorbent assay [ELISA]). Additionally, a kidney offer expressing the HLA-A25 phenotype was not acceptable for the patient due to a positive complement-dependent cytotoxicity assay (CDC)-based cross-match. The question arose whether this reactivity might be due to auto-reactive antibodies directed against the HLA-A25 phenotype. However, no auto-reactive antibodies were detectable using either the CDC-based or the antibody monitoring system-ELISA-based cross-match assays. Consequently the patient was re-examined at high resolution showing the rare HLA-A*25:14 genotype. This case showed that rare alleles may result in allele-specific antibodies directed against the common variants, thus leading to unexpected positive cross-match results against apparently matched allografts. PMID:22664032

Schlaf, G; Radam, C; Wahle, A; Altermann, W W

2012-06-01

399

A class of neutral functional differential equations.  

NASA Technical Reports Server (NTRS)

Formulation and study of the initial value problem for neutral functional differential equations. The existence, uniqueness, and continuation of solutions to this problem are investigated, and an analysis is made of the dependence of the solutions on the initial conditions and parameters, resulting in the derivation of a continuous dependence theorem in which the fundamental mathematical principles underlying the continuous dependence problem for a very general system of nonlinear neutral functional differential equations are separated out.

Melvin, W. R.

1972-01-01

400

Broadband Internet: Net Neutrality versus Open Access  

Microsoft Academic Search

“Network neutrality” and “open access” are two policies designed to preserve openness on the Internet. Open access mandates openness of conduits (e.g. television cable and DSL) to service providers (e.g. America Online), while network neutrality mandates openness to advanced content (streaming video, interactive e-commerce, etc.). We develop a systems model with free entry and competition in all three industry segments

Christiaan Hogendorn

2006-01-01

401

Broadband Internet: net neutrality versus open access  

Microsoft Academic Search

“Network neutrality” and “open access” are two policies designed to preserve openness on the Internet. Open access mandates\\u000a openness of conduits (e.g. television cable and DSL) to intermediaries (e.g. America Online), while network neutrality mandates\\u000a openness to advanced content (streaming video, interactive e-commerce, etc.). We develop a systems model with free entry and\\u000a competition in all three industry segments (conduits,

Christiaan Hogendorn

2007-01-01

402

On the Possibility of Constructive Neutral Evolution  

Microsoft Academic Search

.   The neutral theory often is presented as a theory of ``noise'' or silent changes at an isolated ``molecular level,'' relevant\\u000a to marking the steady pace of divergence, but not to the origin of biological structure, function, or complexity. Nevertheless,\\u000a precisely these issues can be addressed in neutral models, such as those elaborated here with regard to scrambled ciliate\\u000a genes,

Arlin Stoltzfus; J Mol Evol

1999-01-01

403

Evaluation and clinical interpretation of hypergammaglobulinemia E: differentiating atopy from immunodeficiency.  

PubMed

Increases in total serum IgE levels can be observed in many diverse conditions, from infection to atopy to primary immunodeficiency. The differentiation of atopy from immunodeficiency most often is made on a clinical basis, after taking findings from history, physical examination, and laboratory studies into consideration. However, total IgE level is neither a sensitive nor a specific diagnostic marker for any particular disease and, therefore, should not be relied on to establish a diagnosis of either atopy or primary immunodeficiency. PMID:18450128

Pien, Gary C; Orange, Jordan S

2008-04-01

404

Granulomatous enteropathy in common variable immunodeficiency: a cause of chronic diarrhoea.  

PubMed Central

Gastrointestinal disease is a well recognized feature in patients with common variable immunodeficiency, and is often due to infection with a variety of organisms. Symptoms usually improve with appropriate antibiotic therapy and replacement gammaglobulin. We describe three middle-aged female patients with common variable immunodeficiency who had protracted diarrhoea and weight loss. Despite extensive investigation no infectious cause was found. All patients had granulomas distributed throughout the gastrointestinal tract, but no features of inflammatory bowel disease. There was a poor response to gammaglobulin replacement therapy, antibiotics or symptomatic treatment. We suggest that granulomatous enteropathy is another gastrointestinal manifestation of common variable immunodeficiency. Images Figure 1 Figure 2 Figure 3 PMID:1852663

Mike, N.; Hansel, T. T.; Newman, J.; Asquith, P.

1991-01-01

405

Neutral particle kinetics in fusion devices  

SciTech Connect

The theory of neutral particle kinetics treats the transport of mass, momentum, and energy in a plasma due to neutral particles which themselves are unaffected by magnetic fields. This transport affects the global power and particle balances in fusion devices, as well as profile control and plasma confinement quality, particle and energy fluxes onto device components, performance of pumping systems, and the design of diagnostics and the interpretation of their measurements. This paper reviews the development of analytic, numerical, and Monte Carlo methods of solving the time-independent Boltzmann equation describing neutral kinetics. These models for neutral particle behavior typically use adaptations of techniques developed originally for computing neutron transport, due to the analogy between the two phenomena, where charge-exchange corresponds to scattering and ionization to absorption. Progress in the field depends on developing multidimensional analytic methods, and obtaining experimental data for the physical processes of wall reflection, the neutral/plasma interaction, and for processes in fusion devices which are directly related to neutral transport, such as H/sub ..cap alpha../ emission rates, plenum pressures, and charge-exchange emission spectra.

Tendler, M.; Heifetz, D.

1986-05-01

406

46 CFR 120.376 - Grounded distribution systems (Neutral grounded).  

Code of Federal Regulations, 2010 CFR

...false Grounded distribution systems (Neutral grounded). 120...FOR MORE THAN 49 PASSENGERS ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 120.376 Grounded distribution systems (Neutral grounded)....

2010-10-01

407

46 CFR 183.376 - Grounded distribution systems (neutral grounded).  

Code of Federal Regulations, 2010 CFR

...false Grounded distribution systems (neutral grounded). 183...VESSELS (UNDER 100 GROSS TONS) ELECTRICAL INSTALLATION Power Sources and Distribution Systems § 183.376 Grounded distribution systems (neutral grounded)....

2010-10-01

408

Cytogenetic study of Kaposi's sarcoma associated with acquired immunodeficiency syndrome.  

PubMed

We performed cytogenetic studies on direct preparations and short-term cultures from Kaposi's sarcoma cells obtained from malignant pericardial effusion. The patient, a 46-year-old man with human immunodeficiency virus infection, initially presented with metastatic Kaposi's sarcoma. Despite therapy, his tumor proved aggressive, and the patient died of widespread pulmonary involvement nine months after diagnosis. Cytogenetic analysis revealed a predominant karyotype of 48,X,-Y, t(2;7)(q32;q36), +der(5)t(5;15)(q?15;q?15), -7, +del(7)(p15), +del(7)(p15), +der(8)t(8;D or G)(q24;p11.2), del(10)(p13), dup(12)(q24), t(18;20)(q21;q13). This case is described in relation to other published cytogenetic studies of this tumor. PMID:3395219

Saikevych, I A; Mayer, M; White, R L; Ho, R C

1988-08-01

409

A new immunodeficient mouse model for human myoblast transplantation.  

PubMed

Design of efficient transplantation strategies for myoblast-based gene therapies in humans requires animal models in which xenografts are tolerated for long periods of time. In addition, such recipients should be able to withstand pretransplantation manipulations for enhancement of graft growth. Here we report that a newly developed immunodeficient mouse carrying two known mutations (the recombinase activating gene 2, RAG2, and the common cytokine receptor gamma, gammac) is a candidate fulfilling these requirements. Skeletal muscles from RAG2(-/-)/gammac(-/-) double mutant mice recover normally after myotoxin application or cryolesion, procedures commonly used to induce regeneration and improve transplantation efficiency. Well-differentiated donor-derived muscle tissue could be detected up to 9 weeks after transplantation of human myoblasts into RAG2(-/-)/gammac(-/-) muscles. These results suggest that the RAG2(-/-)/gammac(-/-) mouse model will provide new opportunities for human muscle research. PMID:11339898

Cooper, R N; Irintchev, A; Di Santo, J P; Zweyer, M; Morgan, J E; Partridge, T A; Butler-Browne, G S; Mouly, V; Wernig, A

2001-05-01

410

Gamma Interferon Primes Productive Human Immunodeficiency Virus Infection in Astrocytes  

PubMed Central

Considerable controversy exists over whether astrocytes can support human immunodeficiency virus (HIV) infection. We evaluated the impact of three cytokines critical to the development of HIV neuropathogenesis, gamma interferon (IFN-?), granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha, on priming astrocytes for HIV infection. We demonstrate that IFN-? was the most potent in its ability to facilitate substantial productive HIV infection of an astroglioma cell line (U87MG) and human fetal astrocytes (HFA). The mechanism of IFN-?-mediated priming of HIV in HFA is unlikely to be at the level of up-regulation of receptors and coreceptors relevant to HIV entry. These data demonstrate that cytokine priming can alter HIV replication in astrocytes. PMID:16352578

Carroll-Anzinger, Deborah; Al-Harthi, Lena

2006-01-01

411

Human immunodeficiency virus type 2 multiply spliced transcripts.  

PubMed

Viral transcripts, particularly those of the regulatory genes (e.g., rev) in lymphocytic cells chronically infected with human immunodeficiency virus type 2, consist of two types, differing in the structure of the leader sequence derived from the 5' long terminal repeat (LTR). Some transcripts undergo a specific splicing event within the 5' LTR, removing an intron consisting of a part of the R region whereas others do not. Because this spliced-out R region is a part of the trans-activation response element (TAR), it could influence trans-activator (Tat)-mediated trans-activation of viral gene expression. Moreover, this part of the R region is predicted to contain a stable secondary structure that could affect the efficiency of translation of the transcripts without this splicing. Thus, the 5' LTR splicing could have important consequences for virus replication, latency, and pathogenicity. PMID:8512748

Chatterjee, P; Garzino-Demo, A; Swinney, P; Arya, S K

1993-04-01

412

Directional budding of human immunodeficiency virus from monocytes.  

PubMed Central

Time-lapse cinematography revealed that activated human immunodeficiency virus (HIV)-infected monocytes crawl along surfaces, putting forward a leading pseudopod. Scanning electron micrographs showed monocyte pseudopods associated with spherical structures the size of HIV virions, and transmission electron micrographs revealed HIV virions budding from pseudopods. Filamentous actin (F-actin) was localized by electron microscopy in the pseudopod by heavy meromyosin decoration. Colocalization of F-actin and p24 viral antigen by light microscopy immunofluorescence indicated that F-actin and virus were present on the same pseudopod. These observations indicate that monocytes produce virus from a leading pseudopod. We suggest that HIV secretion at the leading edges of donor monocytes/macrophages may be an efficient way for HIV to infect target cells. PMID:8709212

Perotti, M E; Tan, X; Phillips, D M

1996-01-01

413

A new intravenous immunoglobulin (BIVIGAM®) for primary humoral immunodeficiency.  

PubMed

Human immunoglobulin G administered intravenously or subcutaneously is used to prevent infections in patients with primary antibody deficiencies. Intravenous immunoglobulin (IVIG) preparations have improved over the years and have evolved from immune serum globulin that is injected intramuscularly or subcutaneously at relatively low doses (100-150 mg/kg per month). IVIG products are currently available in different concentrations and compositions and can deliver up to 2 g/kg or more per infusion with few side effects. This report describes the properties and clinical trial results of BIVIGAM(®), a new IVIG product. We also discuss how improvements in intravenous immunoglobulin manufacturing and formulation have improved clinical outcomes in patients with primary immunodeficiencies, also benefiting patients with other immunological disorders. PMID:24527947

Wasserman, Richard L

2014-03-01

414

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

415

DNA repair: the link between primary immunodeficiency and cancer.  

PubMed

The adaptive component of the immune system depends greatly on the generation of genetic diversity provided by lymphocyte-specific genomic rearrangements. V(D)J recombination, class switch recombination (CSR), and somatic hypermutation (SHM) constitute complex and vulnerable processes that are orchestrated by a multitude of DNA repair pathways. When inherited defects in certain DNA repair proteins are present, lymphocyte development can be compromised and, consequently, patients can develop primary immunodeficiencies (PIDs). PID patients often have a strong predisposition for cancer development as a result of genomic instability generated from defective DNA repair mechanisms. Tumors of lymphoid origin are one of the most common PID-associated cancers, likely due to DNA lesions resulting from defective V(D)J, CSR, and SHM. In this review, we describe PID syndromes that confer an increased risk for cancer development. Furthermore, we discuss the role of the affected proteins in tumorigenesis/lymphomagenesis. PMID:22236430

de Miranda, Noel Fcc; Björkman, Andrea; Pan-Hammarström, Qiang

2011-12-01

416

Coreceptor specificity of temporal variants of simian immunodeficiency virus Mne.  

PubMed

The simian immunodeficiency virus (SIV) Mne envelope undergoes genetic changes that alter tropism, syncytium-inducing capacity, and antigenic properties of the emerging variant virus population during the course of an infection. Here we investigated whether the mutations in envelope of SIVMne also influence coreceptor usage. The data demonstrate that the infecting macrophage-tropic SIVMne clone as well as the envelope variants that are selected during the course of disease progression all recognize both CCR5 and Bob (GPR15) but not Bonzo (STRL33), CXCR4, or CCR3. Although it remains to be determined if there are other coreceptors specific for dualtropic or T-cell-tropic variants of SIVMne that emerge during late stages of infection, these data suggest that such SIV variants that evolve in pathogenic infections do not lose the ability to recognize CCR5 or Bob/GPR15. PMID:9882375

Kimata, J T; Gosink, J J; KewalRamani, V N; Rudensey, L M; Littman, D R; Overbaugh, J

1999-02-01

417

Systemic Spironucleosis In Two Immunodeficient Rhesus Macaques (Macaca mulatta)  

PubMed Central

Spironucleus spp. are parasites of fish and terrestrial vertebrates including mice and turkeys that rarely cause extraintestinal disease. Two rhesus macaques (Macaca mulatta) were experimentally inoculated with simian immunodeficiency virus mac251 (SIVmac251). Both progressed to simian acquired immune deficiency syndrome (SAIDS) within one year of inoculation and, in addition to common opportunistic infections including rhesus cytomegalovirus, rhesus lymphocryptovirus, and rhesus adenovirus, developed systemic protozoal infections. In the first case, the protozoa were associated with colitis, multifocal abdominal abscessation, and lymphadenitis. In the second case they one of a number of organisms associated with extensive pyogranulomatous pneumonia and colitis. Ultrastructural, molecular, and phylogenetic analysis revealed the causative organism to be a species of Spironucleus closely related to Spironucleus meleagridis of turkeys. This is the first report of extraintestinal infection with Spironucleus sp. in higher mammals and further expands the list of opportunistic infections found in immunocompromised rhesus macaques. PMID:20351359

Bailey, C; Kramer, J; Mejia, A; MacKey, J; Mansfield, KG; Miller, AD

2011-01-01

418

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

419

[Necrotising fasciitis in a patient with common variable immunodeficiency].  

PubMed

Necrotizing fasciitis is a severe infection that leads to necrosis of the tissues and systemic involvement, with a rapid progress and a fatal outcome. Although this condition is rare, it must be suspected and rapidly treated, as the prognosis depends on this. The treatment is based on immediate surgery, wide spectrum antibiotic treatment, and support measures in a critical care unit. We present the case of a patient who was admitted to Recovery room after surgical debridement due to suspicion of fasciitis. The patient also had a common variable immunodeficiency or hypogammaglobulinaemia, characterised by a B lymphocyte deficiency, as well as on treatment with methotrexate for Crohn's disease. Both produced an immune deficiency. After 11 days of treatment there was a clinical, analytical and haemodynamic improvement, and she was discharged. PMID:22575775

Sanjuán Álvarez, M; Sánchez Zamora, P; González Salvador, Y; García Rueda, A; Herrero Trujillano, M; Rodríguez Bertos, C

2013-03-01

420

Targeting Human Immunodeficiency Virus Type 1 Assembly, Maturation and Budding  

PubMed Central

The targets for licensed drugs used for the treatment of human immunodeficiency virus type 1 (HIV-1) are confined to the viral reverse transcriptase (RT), protease (PR), and the gp41 transmembrane protein (TM). While currently approved drugs are effective in controlling HIV-1 infections, new drug targets and agents are needed due to the eventual emergence of drug resistant strains and drug toxicity. Our increased understanding of the virus life-cycle and how the virus interacts with the host cell has unveiled novel mechanisms for blocking HIV-1 replication. This review focuses on inhibitors that target the late stages of virus replication including the synthesis and trafficking of the viral polyproteins, viral assembly, maturation and budding. Novel approaches to blocking the oligomerization of viral enzymes and the interactions between viral proteins and host cell factors, including their feasibility as drug targets, are discussed. PMID:21901072

Wapling, Johanna; Srivastava, Seema; Shehu-Xhilaga, Miranda; Tachedjian, Gilda

2007-01-01

421

Non-Neutral Plasma Physics IV: Workshop on Non-Neutral Plasmas  

Microsoft Academic Search

OAK- B135 - Proceedings: Non-Neutral Plasma Physics IV; Workshop on Non-Neutral Plasmas, San Diego Ca 2001 (AIP Conf.Proc. Vol 606) F. Anderegg, L. Schweikhard and C.F. Driscoll, editors; AIP, New York, 2002 (738 pages). The preface summarized workshop content and activities. The 89 scientific articles describe current non-neutral plasma research in the areas of antimatter plasmas, strongly coupled plasmas, beams,

F. Anderegg; L. Schweikhard; C. F. Driscoll

2001-01-01

422

Lentivirus Vectors Using Human and Simian Immunodeficiency Virus Elements  

PubMed Central

Lentivirus vectors based on human immunodeficiency virus (HIV) type 1 (HIV-1) constitute a recent development in the field of gene therapy. A key property of HIV-1-derived vectors is their ability to infect nondividing cells. Although high-titer HIV-1-derived vectors have been produced, concerns regarding safety still exist. Safety concerns arise mainly from the possibility of recombination between transfer and packaging vectors, which may give rise to replication-competent viruses with pathogenic potential. We describe a novel lentivirus vector which is based on HIV, simian immunodeficiency virus (SIV), and vesicular stomatitis virus (VSV) and which we refer to as HIV/SIVpack/G. In this system, an HIV-1-derived genome is encapsidated by SIVmac core particles. These core particles are pseudotyped with VSV glycoprotein G. Because the nucleotide homology between HIV-1 and SIVmac is low, the likelihood of recombination between vector elements should be reduced. In addition, the packaging construct (SIVpack) for this lentivirus system was derived from SIVmac1A11, a nonvirulent SIV strain. Thus, the potential for pathogenicity with this vector system is minimal. The transduction ability of HIV/SIVpack/G was demonstrated with immortalized human lymphocytes, human primary macrophages, human bone marrow-derived CD34+ cells, and primary mouse neurons. To our knowledge, these experiments constitute the first demonstration that the HIV-1-derived genome can be packaged by an SIVmac capsid. We demonstrate that the lentivirus vector described here recapitulates the biological properties of HIV-1-derived vectors, although with increased potential for safety in humans. PMID:10074131

White, Sarah M.; Renda, Matthew; Nam, Na-Yon; Klimatcheva, Ekaterina; Zhu, Yonghong; Fisk, Jennifer; Halterman, Mark; Rimel, Bobbie J.; Federoff, Howard; Pandya, Snehal; Rosenblatt, Joseph D.; Planelles, Vicente

1999-01-01

423

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, Francois

2013-01-01

424

[Study of molecular function of proteins in human immunodeficiency virus].  

PubMed

Human immunodeficiency virus (HIV) has no more than nine genes expressing approximately twenty proteins. When T lymphocytes and macrophages in a body are infected with HIV, these proteins work in turn at specific time and location, causing acquired immunodeficiency syndrome (AIDS), a disease yet to be overcome. Since the elucidation of molecular mechanism of HIV proteins should lead to remedy of AIDS, the author has been engaged in the study of HIV protein in the past decade. Described herein are viral protein X (Vpx), uniquely found in HIV-2, and its homologous protein Vpr found both in HIV-1 and -2. We found that Vpx enhances genome nuclear import in T lymphocytes, and is critical for reverse transcription of viral RNA in macrophages. This finding on the function in macrophages corrected long-term misleading belief. Furthermore, functional region mapping of Vpx was performed. In 2011, the protein SAMHD1 was identified as the host restriction factor counteracted by Vpx, by foreign researchers. After that, our independent study demonstrated the presence of SAMHD1-independent functions of Vpx in T cells, in addition to its SAMHD1-dependent functions in macrophages. Another topic of this review is Gag protein. Recently, it has reported by overseas researchers that PI(4,5)P2 (one of phosphoinositide) regulates Pr55(Gag) localization and assembly. In this study, we determined the binding affinity between N-terminal MA domain of Pr55(Gag) and various phosphoinositide derivatives using surface plasmon resonance. The results suggested that both negatively charged inositol phosphates and hydrophobic acyl chain are required for the MA binding. PMID:24088354

Fujita, Mikako

2013-01-01

425

Immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF)  

PubMed Central

The Immunodeficiency, Centromeric region instability, Facial anomalies syndrome (ICF) is a rare autosomal recessive disease described in about 50 patients worldwide and characterized by immunodeficiency, although B cells are present, and by characteristic rearrangements in the vicinity of the centromeres (the juxtacentromeric heterochromatin) of chromosomes 1 and 16 and sometimes 9. Other variable symptoms of this probably under-diagnosed syndrome include mild facial dysmorphism, growth retardation, failure to thrive, and psychomotor retardation. Serum levels of IgG, IgM, IgE, and/or IgA are low, although the type of immunoglobulin deficiency is variable. Recurrent infections are the presenting symptom, usually in early childhood. ICF always involves limited hypomethylation of DNA and often arises from mutations in one of the DNA methyltransferase genes (DNMT3B). Much of this DNA hypomethylation is in 1qh, 9qh, and 16qh, regions that are the site of whole-arm deletions, chromatid and chromosome breaks, stretching (decondensation), and multiradial chromosome junctions in mitogen-stimulated lymphocytes. By an unknown mechanism, the DNMT3B deficiency that causes ICF interferes with lymphogenesis (at a step after class switching) or lymphocyte activation. With the identification of DNMT3B as the affected gene in a majority of ICF patients, prenatal diagnosis of ICF is possible. However, given the variety of DNMT3B mutations, a first-degree affected relative should first have both alleles of this gene sequenced. Treatment almost always includes regular infusions of immunoglobulins, mostly intravenously. Recently, bone marrow transplantation has been tried. PMID:16722602

Ehrlich, Melanie; Jackson, Kelly; Weemaes, Corry

2006-01-01

426

Non-M variants of human immunodeficiency virus type 1.  

PubMed

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; Plantier, Jean-Christophe

2013-07-01

427

Com?l-Netherton syndrome - defined as primary immunodeficiency  

PubMed Central

Background Mutations in SPINK5, encoding the serine protease inhibitor LEKTI, cause Comèl-Netherton syndrome, an autosomal-recessive disease characterized by congenital ichthyosis, bamboo hair, and atopic diathesis. Despite increased frequency of infections, the immunocompetence of Comèl-Netherton syndrome patients has not been extensively investigated. Objective To define Comèl-Netherton syndrome as a primary immunodeficiency and to explore the benefit of IVIG replacement therapy. Methods We enrolled nine patients with Comèl-Netherton syndrome, sequenced SPINK5, and analyzed LEKTI expression by immunohistochemistry. Immune function was assessed by measuring cognate immunity, serum cytokine-levels and natural killer cell cytotoxicity. Results All patients presented with recurrent skin infections caused predominantly by Staphylococcus aureus. All but one reported recurrent respiratory tract infections; 78% had sepsis and/or pneumonia; 67% suffered from recurrent gastroenteritis and failure to thrive. Mutations in SPINK5 – including six novel mutations- were identified in eight patients. LEKTI expression was decreased or absent in all patients. Immunologic evaluation revealed reduced memory B cells and defective responses to vaccination with Pneumovax® and bacteriophage phiX174, characterized by impaired antibody amplification and class-switching. Immune dysregulation was suggested by a skewed TH1-phenotype and elevated proinflammatory cytokine levels, while serum concentrations of the chemokine RANTES and NK cell cytotoxicity were decreased. Treatment with intravenous immunoglobulin substitution resulted in remarkable clinical improvement and temporarily increased NK cell cytotoxicity. Conclusion These data provide new insights into the immunopathology of Comèl-Netherton syndrome and demonstrate that this multisystem disorder, characterized by lack of LEKTI expression in epithelial cells, is complicated by cognate and innate immunodeficiency that responds favorably to IVIG therapy. PMID:19683336

Renner, Ellen D; Hartl, Dominik; Rylaarsdam, Stacey; Young, Marguerite L; Monaco-Shawver, Linda; Kleiner, Gary; Markert, M Louise; Stiehm, E Richard; Belohradsky, Bernd H; Upton, Melissa P.; Torgerson, Troy R; Orange, Jordan S; Ochs, Hans D

2013-01-01

428

[Common variable immunodeficiency. Epidemiology and clinical manifestations in 69 patients].  

PubMed

Common variable immunodeficiency (CVID) is characterized by an impaired antibody production and an increased susceptibility to recurrent infections of the respiratory tract, mainly by extracellular encapsulated bacteria. We analyzed the clinical characteristics of 69 patients evaluated over a period of 10 years at three centers in the city of Buenos Aires. At the onset of the study 14 patients were on follow up, and at its end the number of patients reached to 60. Most of them consulted for infection or hypogammaglobulinemia and nearly half had an established diagnosis of immunodeficiency. Sixty-five (94.2%) patients had infections by encapsulated bacteria, four (6.1%) sepsis and two tuberculosis. The average age of onset of infectious symptoms was 18.1 years; the average age at diagnosis was 29.6 years and the delay to diagnosis 11.9 years. Forty one (59.4%) patients reported a history of recurrent or chronic diarrhea. In 22 (31.9%) 13 autoimmune diseases were diagnosed, being the most frequent the hematological disorders and hypothyroidism. Eight patients had histological polyclonal lymphoproliferation, four (5.8%) with granulomatous disease affecting the liver, the larynx and/or the skin; and four as lymphoid interstitial pneumonitis (LIP). Nineteen (27.5%) patients had splenomegaly and 23/57 (40.3%) images suggestive of lymphocytic or granulomatous processes (including the 4 with LIP) in the chest CT. Three (4.3%) patients developed B cell lymphoma, four (5.8%) stomach adenocarcinoma and one breast cancer. The study had a median follow-up of 54 months, range 1-353 and four patients (5.8%) died during the follow up. PMID:23924529

Fernández Romero, Diego S; Juri, María C; Paolini, María V; Malbrán, Alejandro

2013-01-01

429

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

430

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

431

Rapid High-Level Production of Functional HIV Broadly Neutralizing Monoclonal Antibodies in Transient Plant Expression Systems  

PubMed Central

Passive immunotherapy using anti-HIV broadly neutralizing monoclonal antibodies (mAbs) has shown promise as an HIV treatment, reducing mother-to-child-transmission (MTCT) of simian/human immunodeficiency virus (SHIV) in non-human primates and decreasing viral rebound in patients who ceased receiving anti-viral drugs. In addition, a cocktail of potent mAbs may be useful as mucosal microbicides and provide an effective therapy for post-exposure prophylaxis. However, even highly neutralizing HIV mAbs used today may lose their effectiveness if resistance occurs, requiring the rapid production of new or engineered mAbs on an ongoing basis in order to counteract the viral resistance or the spread of a certain HIV-1 clade in a particular region or patient. Plant-based expression systems are fast, inexpensive and scalable and are becoming increasingly popular for the production of proteins and monoclonal antibodies. In the present study, Agrobacterium-mediated transient transfection of plants, utilizing two species of Nicotiana, have been tested to rapidly produce high levels of an HIV 89.6P?140env and several well-studied anti-HIV neutralizing monoclonal antibodies (b12, 2G12, 2F5, 4E10, m43, VRC01) or a single chain antibody construct (m9), for evaluation in cell-based viral inhibition assays. The protein-A purified plant-derived antibodies were intact, efficiently bound HIV envelope, and were equivalent to, or in one case better than, their counterparts produced in mammalian CHO or HEK-293 cells in both neutralization and antibody dependent viral inhibition assays. These data indicate that transient plant-based transient expression systems are very adaptable and could rapidly generate high levels of newly identified functional recombinant HIV neutralizing antibodies when required. In addition, they warrant detailed cost-benefit analysis of prolonged incubation in plants to further increase mAb production. PMID:23533588

Rosenberg, Yvonne; Sack, Markus; Montefiori, David; Forthal, Donald; Mao, Lingjun; -Abanto, Segundo Hernandez; Urban, Lori; Landucci, Gary; Fischer, Rainer; Jiang, Xiaoming

2013-01-01

432

Magnitude and breadth of a non-protective neutralizing antibody response in an efficacy trial of a candidate HIV-1 gp120 vaccine (AIDSVAX(TM) B/B)  

PubMed Central

Background A candidate vaccine consisting of human immunodeficiency virus type 1 (HIV-1) subunit gp120 protein (AIDSVAX™ B/B) was found previously to be non-protective despite strong antibody responses against the vaccine antigens. We assessed the magnitude and breadth of neutralizing antibody responses in this trial. Methods Neutralizing antibodies were measured against highly sensitive (tier 1) and moderately sensitive (tier 2) strains of HIV-1 subtype B in two independent assays. Vaccine recipients were stratified by gender, race and high versus low behavioral risk of HIV-1 acquisition. Results Most vaccine recipients mounted potent neutralizing antibody responses against HIV-1MN and a subset of other tier 1 viruses. Occasional weak neutralizing activity was detected against tier 2 viruses. The response against tier 1 and tier 2 viruses was significantly stronger in women than in men. Race and behavioral risk of HIV-1 acquisition had no significant effect on the response. Prior vaccination had little effect on the neutralizing antibody response that arose post infection. Conclusions Weak overall neutralizing antibody responses against tier 2 viruses is consistent with a lack of protection in this trial. The magnitude and breadth of neutralization reported here should be useful for identifying improved vaccines. PMID:20608874

Gilbert, Peter; Wang, Maggie; Wrin, Terri; Petropoulos, Chris; Gurwith, Marc; Sinangil, Faruk; D'Souza, Patricia; Rodriguez-Chavez, Isaac R.; DeCamp, Allan; Giganti, Mark; Berman, Phillip W.; Self, Steve G.; Montefiori, David C.

2010-01-01

433

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

434

Cellular Gene Expression Profiles in Rhesus Macaques Challenged Mucosally with a Pathogenic R5 Tropic Simian Human Immunodeficiency Virus Isolate  

PubMed Central

Abstract Insights into the host factors that contribute to an effective antiviral immune response may be obtained by examining global gene expression in simian human immunodeficiency virus (SHIV)-infected nonhuman primates that exhibit different virological outcomes. Immune responses and gene expression profiles in peripheral blood mononuclear cells (PBMCs) were compared between animals that controlled or did not control viremia after infection. Rectal inoculation of eight rhesus macaques with R5-tropic SHIVSF162P3 resulted in a high level of plasma viremia during the acute phase of infection. The viremia was controlled to below levels of detection in six of these animals at the set point (controllers), whereas two animals had persistent viremia throughout the 140 wk that the animals were monitored (non-controllers). CD4+ T-cell counts declined slightly in both controllers and non-controllers in the acute phase of infection, but CD4+ T-cell counts continued to decline only in the non-controllers. Neutralizing antibodies to the challenge virus were variable and could not account for the control of viremia. However, analysis of the cellular gene expression profiles in the PBMCs from both groups of animals revealed distinctive gene expression patterns between controllers and non-controllers. Using the paired LPE test, 59 genes with p values <0.01 were identified and specific differences in the gene expression profiles in PBMCs from controllers versus non-controllers were detected. PMID:19115930

Pise-Masison, Cynthia A.; Radonovich, Michael