LIVIVO - Search results -

Search results

Result 1 - 10 of total 20

Search options

Article ; Online: COBRA HA elicits hemagglutination-inhibition antibodies against a panel of H3N2 influenza virus co-circulating variants.

Wong, Terianne M / Allen, James D / Bebin-Blackwell, Anne-Gaelle / Carter, Donald M / Alefantis, Timothy / DiNapoli, Joshua / Kleanthous, Harold / Ross, Ted M

Journal of virology

2017

Abstract: Each influenza season, a set of wild-type viruses, representing one H1N1, one H3N2, 1-2 influenza B isolates, are selected for inclusion in the annual seasonal influenza vaccine. In order to develop broadly reactive subtype specific influenza vaccines, a ...

Abstract	Each influenza season, a set of wild-type viruses, representing one H1N1, one H3N2, 1-2 influenza B isolates, are selected for inclusion in the annual seasonal influenza vaccine. In order to develop broadly reactive subtype specific influenza vaccines, a methodology called computationally optimized broadly reactive antigens (COBRA) was used to design novel hemagglutinin (HA) vaccine immunogens. COBRA technology was effectively used to design HA immunogens that elicited antibodies that neutralized H5N1 and H1N1 isolates. In this report, the development and characterization of seventeen prototype H3N2 COBRA HA proteins were screened in mice and ferrets for the elicitation of antibodies with HAI activity against human seasonal H3N2 viruses that were isolated over the last 48 years. The most effective COBRA HA vaccine regimens elicited antibodies with broader HAI activity against a panel of H3N2 viruses compared to wild-type H3 HA vaccines. The top leading COBRA HA candidates were tested against co-circulating variants. These variants were not efficiently detected by antibodies elicited by the wild-type HA from viruses selected as the vaccine candidates. The T-11 COBRA HA vaccine elicited antibodies with HAI and neutralization activity against all co-circulating variants from 2004-2007. This is the first report demonstrating broader breadth of vaccine induced antibodies against co-circulating H3N2 strains compared to the wild-type HA antigens that were represented in commercial influenza vaccines.
Language	English
Publishing date	2017-10-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01581-17
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 609: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article: Interaction of HTLV-1 Tax protein with calreticulin: implications for Tax nuclear export and secretion.

Alefantis, Timothy / Flaig, Katherine E / Wigdahl, Brian / Jain, Pooja

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2007 Volume 61, Issue 4, Page(s) 194–200

Abstract: Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 transcriptional transactivator protein Tax plays an integral role in ... ...

Abstract	Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 transcriptional transactivator protein Tax plays an integral role in virus replication and disease progression. Traditionally, Tax is described as a nuclear protein where it performs its primary role as a transcriptional transactivator. However, recent studies have clearly shown that Tax can also be localized to the cytoplasm where it has been shown to interact with a number of host transcription factors most notably NF-kappaB, constitutive expression of which is directly related to the T cell transforming properties of Tax in ATL patients. The presence of a functional nuclear export signal (NES) within Tax and the secretion of full-length Tax have also been demonstrated previously. Additionally, release of Tax from HTLV-1-infected cells and the presence of cell-free Tax was demonstrated in the CSF of HAM/TSP patients suggesting that the progression to HAM/TSP might be mediated by the ability of Tax to function as an extracellular cytokine. Therefore, in both ATL and HAM/TSP Tax nuclear export and nucleocytoplasmic shuttling may play a critical role, the mechanism of which remains unknown. In this study, we have demonstrated that the calcium binding protein calreticulin interacts with Tax by co-immunoprecipitation. This interaction was found to localize to a region at or near the nuclear membrane. In addition, differential expression of calreticulin was demonstrated in various cell types that correlated with their ability to retain cytoplasmic Tax, particularly in astrocytes. Finally, a comparison of a number of HTLV-1-infected T cell lines to non-infected T cells revealed higher expression of calreticulin in infected cells implicating a direct role for this protein in HTLV-1 infection.
MeSH term(s)	Active Transport, Cell Nucleus ; Animals ; Blotting, Western ; Calreticulin/biosynthesis ; Calreticulin/metabolism ; Cell Line ; Cell Nucleus/metabolism ; Cricetinae ; Gene Products, tax/metabolism ; Gene Products, tax/secretion ; Human T-lymphotropic virus 1/physiology ; Humans ; Immunoprecipitation ; Plasmids
Chemical Substances	Calreticulin ; Gene Products, tax
Language	English
Publishing date	2007-05
Publishing country	France
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2007.02.005
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

In stock of ZB MED Cologne/Königswinter

Ud II Zs.198: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Design and Characterization of a Computationally Optimized Broadly Reactive Hemagglutinin Vaccine for H1N1 Influenza Viruses.

Carter, Donald M / Darby, Christopher A / Lefoley, Bradford C / Crevar, Corey J / Alefantis, Timothy / Oomen, Raymond / Anderson, Stephen F / Strugnell, Tod / Cortés-Garcia, Guadalupe / Vogel, Thorsten U / Parrington, Mark / Kleanthous, Harold / Ross, Ted M

Journal of virology

2016 Volume 90, Issue 9, Page(s) 4720–4734

Abstract: Unlabelled: One of the challenges of developing influenza A vaccines is the diversity of antigenically distinct isolates. Previously, a novel hemagglutinin (HA) for H5N1 influenza was derived from a methodology termed computationally optimized broadly ... ...

Abstract	Unlabelled: One of the challenges of developing influenza A vaccines is the diversity of antigenically distinct isolates. Previously, a novel hemagglutinin (HA) for H5N1 influenza was derived from a methodology termed computationally optimized broadly reactive antigen (COBRA). This COBRA HA elicited a broad antibody response against H5N1 isolates from different clades. We now report the development and characterization of a COBRA-based vaccine for both seasonal and pandemic H1N1 influenza virus isolates. Nine prototype H1N1 COBRA HA proteins were developed and tested in mice using a virus-like particle (VLP) format for the elicitation of broadly reactive, functional antibody responses and protection against viral challenge. These candidates were designed to recognize H1N1 viruses isolated within the last 30 years. In addition, several COBRA candidates were designed based on sequences of H1N1 viruses spanning the past 100 years, including modern pandemic H1N1 isolates. Four of the 9 H1N1 COBRA HA proteins (X1, X3, X6, and P1) had the broadest hemagglutination inhibition (HAI) activity against a panel of 17 H1N1 viruses. These vaccines were used in cocktails or prime-boost combinations. The most effective regimens that both elicited the broadest HAI response and protected mice against a pandemic H1N1 challenge were vaccines that contained the P1 COBRA VLP and either the X3 or X6 COBRA VLP vaccine. These mice had little or no detectable viral replication, comparable to that observed with a matched licensed vaccine. This is the first report describing a COBRA-based HA vaccine strategy that elicits a universal, broadly reactive, protective response against seasonal and pandemic H1N1 isolates. Importance: Universal influenza vaccine approaches have the potential to be paradigm shifting for the influenza vaccine field, with the goal of replacing the current standard of care with broadly cross-protective vaccines. We have used COBRA technology to develop an HA head-based strategy that elicits antibodies against many H1 strains that have undergone genetic drift and has potential as a "subtype universal" vaccine. Nine HA COBRA candidates were developed, and these vaccines were used alone, in cocktails or in prime-boost combinations. The most effective regimens elicited the broadest hemagglutination inhibition (HAI) response against a panel of H1N1 viruses isolated over the past 100 years. This is the first report describing a COBRA-based HA vaccine strategy that elicits a broadly reactive response against seasonal and pandemic H1N1 isolates.
MeSH term(s)	Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/metabolism ; Antibodies, Viral/immunology ; Antibodies, Viral/metabolism ; Antigens, Viral/chemistry ; Antigens, Viral/genetics ; Antigens, Viral/immunology ; Cell Line ; Disease Models, Animal ; Hemagglutination Inhibition Tests ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry ; Hemagglutinin Glycoproteins, Influenza Virus/genetics ; Hemagglutinin Glycoproteins, Influenza Virus/immunology ; Humans ; Immunization ; Influenza A Virus, H1N1 Subtype/classification ; Influenza A Virus, H1N1 Subtype/genetics ; Influenza A Virus, H1N1 Subtype/immunology ; Influenza A Virus, H1N1 Subtype/ultrastructure ; Influenza Vaccines/immunology ; Influenza, Human/prevention & control ; Mice ; Models, Molecular ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/prevention & control ; Phylogeny ; Protein Binding/immunology ; Protein Conformation ; Protein Interaction Domains and Motifs ; Vaccines, Virus-Like Particle/immunology
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Viral ; Antigens, Viral ; Hemagglutinin Glycoproteins, Influenza Virus ; Influenza Vaccines ; Vaccines, Virus-Like Particle
Language	English
Publishing date	2016-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.03152-15
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 609: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: HTLV-1 Tax nucleocytoplasmic shuttling, interaction with the secretory pathway, extracellular signaling, and implications for neurologic disease.

Alefantis, Timothy / Jain, Pooja / Ahuja, Jaya / Mostoller, Kate / Wigdahl, Brian

Journal of biomedical science

2005 Volume 12, Issue 6, Page(s) 961–974

Abstract: The human T cell leukemia virus type 1 (HTLV-1) oncoprotein Tax interacts with numerous cellular pathways promoting both the survival and pathogenesis of the virus in the human population. Tax has been studied extensively with respect to its role in ... ...

Abstract	The human T cell leukemia virus type 1 (HTLV-1) oncoprotein Tax interacts with numerous cellular pathways promoting both the survival and pathogenesis of the virus in the human population. Tax has been studied extensively with respect to its role in transcriptional transactivation and its involvement in the up-regulation of a number of cellular genes during the process of oncogenic transformation. These processes are dependent on Tax localization to the nucleus where it interacts with a number of cellular transcription factors during its course of nuclear action. However, there is mounting evidence suggesting that Tax may shuttle between the nucleus and cytoplasm, localize to several cytoplasmic organelles with subsequent secretion from both Tax-transfected cells as well as HTLV-1-infected cells. In addition, the presence of cell-free Tax in cerebral spinal fluid (CSF) was recently demonstrated to occur during all stages of HAM/TSP. This has brought about an increased interest in the cytoplasmic localization of Tax and the implications this localization may have with respect to the progression of HTLV-1-associated disease processes. This review addresses the functional implications relevant to the localization and accumulation of Tax in the cytoplasm including the Tax amino acid signals and cellular protein interactions that may regulate this process. Specifically, we have discussed three important processes associated with the cytoplasmic localization of Tax. First, the process of Tax shuttling between the nucleus and cytoplasm will be described and how this process may be involved in regulating different transcriptional activation pathways. Second, cytoplasmic localization of Tax will be discussed with relevance to Tax secretion and the interaction of Tax with proteins in the cellular secretory pathway. Finally, the secretion of Tax and the effects of extracellular Tax on HTLV-1 pathogenesis will be addressed.
MeSH term(s)	Active Transport, Cell Nucleus ; Animals ; Cell Nucleus/metabolism ; Cell Physiological Phenomena ; Cytoplasm/metabolism ; Disease Progression ; Gene Products, tax/metabolism ; Gene Products, tax/physiology ; HTLV-I Infections/pathology ; Human T-lymphotropic virus 1/metabolism ; Humans ; Leukemia, T-Cell/metabolism ; Models, Biological ; Nervous System Diseases/metabolism ; Nervous System Diseases/virology ; Protein Transport ; Signal Transduction ; Up-Regulation
Chemical Substances	Gene Products, tax
Language	English
Publishing date	2005-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1193378-1
ISSN	1423-0127 ; 1021-7770
ISSN (online)	1423-0127
ISSN	1021-7770
DOI	10.1007/s11373-005-9026-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4037: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Human T cell leukemia virus type I-induced disease: pathways to cancer and neurodegeneration.

Barmak, Kate / Harhaj, Edward / Grant, Christian / Alefantis, Timothy / Wigdahl, Brian

Virology

2003 Volume 308, Issue 1, Page(s) 1–12

Abstract: Retroviral infection is associated with a number of pathologic abnormalities, including a variety of cancers, immunologic diseases, and neurologic disorders. Shortly after its discovery in 1980, human T cell leukemia virus type I (HTLV-I) was found to be ...

Abstract	Retroviral infection is associated with a number of pathologic abnormalities, including a variety of cancers, immunologic diseases, and neurologic disorders. Shortly after its discovery in 1980, human T cell leukemia virus type I (HTLV-I) was found to be the etiologic agent of both adult T cell leukemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a neurologic disease characterized by demyelinating lesions in both the brain and the spinal cord. Approximately 5-10% of HTLV-I-infected individuals develop either ATL or HAM/TSP. Interestingly, the two diseases have vastly different pathologies and have rarely been found to occur within the same individual. While a number of host and viral factors including virus strain, viral load, and HLA haplotype have been hypothesized to influence disease outcome associated with HTLV-I infection, the relative contributions of such factors to disease pathogenesis have not been fully established. Recent research has suggested that the route of primary viral infection may dictate the course of disease pathogenesis associated with HTLV-I infection. Specifically, mucosal exposure to HTLV-I has been associated with cases of ATL, while primary viral infection based in the peripheral blood has been correlated with progression to HAM/TSP. However, the cellular and molecular mechanisms regulating disease progression resulting from primary viral invasion remain to be elucidated. Although a variety of factors likely influence these mechanisms, the differential immune response mounted by the host against the incoming virus initiated in either the peripheral blood or the mucosal compartments likely plays a key role in determining the outcome of HTLV-I infection. It has been proposed that the route of infection and size of the initial viral inoculum allows HTLV-I to infect different target cell populations, in turn influencing the breadth of the immune response mounted against HTLV-I and affecting disease pathogenesis. A model of HTLV-I-induced disease progression is presented, integrating information regarding the role of several host and viral factors in the genesis of both neoplasia and neurologic disease induced following HTLV-I infection, focusing specifically on differential viral invasion into the bone marrow (BM) and the influence of this event on the virus-specific CD8(+) cytotoxic T lymphocyte (CTL) response that is initiated following HTLV-I infection.
MeSH term(s)	Animals ; Bone Marrow/immunology ; Bone Marrow/virology ; CD8-Positive T-Lymphocytes/immunology ; Disease Progression ; Human T-lymphotropic virus 1/genetics ; Human T-lymphotropic virus 1/pathogenicity ; Humans ; Leukemia-Lymphoma, Adult T-Cell/immunology ; Leukemia-Lymphoma, Adult T-Cell/pathology ; Leukemia-Lymphoma, Adult T-Cell/virology ; Paraparesis, Tropical Spastic/immunology ; Paraparesis, Tropical Spastic/pathology ; Paraparesis, Tropical Spastic/virology
Language	English
Publishing date	2003-03-30
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	200425-2
ISSN	1096-0341 ; 0042-6822
ISSN (online)	1096-0341
ISSN	0042-6822
DOI	10.1016/s0042-6822(02)00091-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ud II Zs.172: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Wealth effects of food and drug administration "Fast Track" designation

Alefantis, Timothy G / Kulkarni, Mukund S / Vora, Premal P

Journal of pharmaceutical finance, economics & policy Vol. 13, No. 3 , p. 41-53

2004 Volume 13, Issue 3, Page(s) 41–53

Author's details	Timothy G. Alefantis; Mukund S. Kulkarni; Premal P. Vora
Keywords	Pharmazeutisches Produkt ; Arzneimittelrecht ; Innovation ; Aktienmarkt ; Börsenkurs ; Vermögenseffekt ; USA
Language	English
Size	graph. Darst
Publisher	Pharmaceutical Products Press
Publishing place	Binghamton, NY
Document type	Article
ZDB-ID	2157583-6
Database	ECONomics Information System

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: A multimechanistic antibody targeting the receptor binding site potently cross-protects against influenza B viruses.

Shen, Chenguang / Chen, Junyu / Li, Rui / Zhang, Mengya / Wang, Guosong / Stegalkina, Svetlana / Zhang, Limin / Chen, Jing / Cao, Jianli / Bi, Xingjian / Anderson, Stephen F / Alefantis, Timothy / Zhang, Minwei / Cai, Xiaoyang / Yang, Kunyu / Zheng, Qingbing / Fang, Mujing / Yu, Hai / Luo, Wenxin /

Zheng, Zizheng / Yuan, Quan / Zhang, Jun / Wai-Kuo Shih, James / Kleanthous, Harry / Chen, Honglin / Chen, Yixin / Xia, Ningshao

Science translational medicine

2017 Volume 9, Issue 412

Abstract: Influenza B virus causes considerable disease burden worldwide annually, highlighting the limitations of current influenza vaccines and antiviral drugs. In recent years, broadly neutralizing antibodies (bnAbs) against hemagglutinin (HA) have emerged as a ...

Abstract	Influenza B virus causes considerable disease burden worldwide annually, highlighting the limitations of current influenza vaccines and antiviral drugs. In recent years, broadly neutralizing antibodies (bnAbs) against hemagglutinin (HA) have emerged as a new approach for combating influenza. We describe the generation and characterization of a chimeric monoclonal antibody, C12G6, that cross-neutralizes representative viruses spanning the 76 years of influenza B antigenic evolution since 1940, including viruses belonging to the Yamagata, Victoria, and earlier lineages. Notably, C12G6 exhibits broad cross-lineage hemagglutination inhibition activity against influenza B viruses and has higher potency and breadth of neutralization when compared to four previously reported influenza B bnAbs. In vivo, C12G6 confers stronger cross-protection against Yamagata and Victoria lineages of influenza B viruses in mice and ferrets than other bnAbs or the anti-influenza drug oseltamivir and has an additive antiviral effect when administered in combination with oseltamivir. Epitope mapping indicated that C12G6 targets a conserved epitope that overlaps with the receptor binding site in the HA region of influenza B virus, indicating why it neutralizes virus so potently. Mechanistic analyses revealed that C12G6 inhibits influenza B viruses via multiple mechanisms, including preventing viral entry, egress, and HA-mediated membrane fusion and triggering antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity responses. C12G6 is therefore a promising candidate for the development of prophylactics or therapeutics against influenza B infection and may inform the design of a truly universal influenza vaccine.
Language	English
Publishing date	2017-10-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.aam5752
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6941: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Self-adjuvanting bacterial vectors expressing pre-erythrocytic antigens induce sterile protection against malaria.

Bergmann-Leitner, Elke S / Hosie, Heather / Trichilo, Jessica / Deriso, Elizabeth / Ranallo, Ryan T / Alefantis, Timothy / Savranskaya, Tatyana / Grewal, Paul / Ockenhouse, Christian F / Venkatesan, Malabi M / Delvecchio, Vito G / Angov, Evelina

Frontiers in immunology

2013 Volume 4, Page(s) 176

Abstract: Genetically inactivated, Gram-negative bacteria that express malaria vaccine candidates represent a promising novel self-adjuvanting vaccine approach. Antigens expressed on particulate bacterial carriers not only target directly to antigen-presenting ... ...

Abstract	Genetically inactivated, Gram-negative bacteria that express malaria vaccine candidates represent a promising novel self-adjuvanting vaccine approach. Antigens expressed on particulate bacterial carriers not only target directly to antigen-presenting cells but also provide a strong danger signal thus circumventing the requirement for potent extraneous adjuvants. E. coli expressing malarial antigens resulted in the induction of either Th1 or Th2 biased responses that were dependent on both antigen and sub-cellular localization. Some of these constructs induced higher quality humoral responses compared to recombinant protein and most importantly they were able to induce sterile protection against sporozoite challenge in a murine model of malaria. In light of these encouraging results, two major Plasmodium falciparum pre-erythrocytic malaria vaccine targets, the Cell-Traversal protein for Ookinetes and Sporozoites (CelTOS) fused to the Maltose-binding protein in the periplasmic space and the Circumsporozoite Protein (CSP) fused to the Outer membrane (OM) protein A in the OM were expressed in a clinically relevant, attenuated Shigella strain (Shigella flexneri 2a). This type of live-attenuated vector has previously undergone clinical investigations as a vaccine against shigellosis. Using this novel delivery platform for malaria, we find that vaccination with the whole-organism represents an effective vaccination alternative that induces protective efficacy against sporozoite challenge. Shigella GeMI-Vax expressing malaria targets warrant further evaluation to determine their full potential as a dual disease, multivalent, self-adjuvanting vaccine system, against both shigellosis, and malaria.
Language	English
Publishing date	2013-07-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2013.00176
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Secretion of the human T cell leukemia virus type I transactivator protein tax.

Alefantis, Timothy / Mostoller, Kate / Jain, Pooja / Harhaj, Edward / Grant, Christian / Wigdahl, Brian

The Journal of biological chemistry

2005 Volume 280, Issue 17, Page(s) 17353–17362

Abstract: Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. The HTLV-I protein Tax is well known as a transcriptional transactivator and inducer of cellular ... ...

Abstract	Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. The HTLV-I protein Tax is well known as a transcriptional transactivator and inducer of cellular transformation. However, it is also known that extracellular Tax induces the production and release of cytokines, such as tumor necrosis factor-alpha and interleukin-6, which have adverse effects on cells of the central nervous system. The cellular process by which Tax exits the cell into the extracellular environment is currently unknown. In most cell types, Tax has been shown to localize primarily to the nucleus. However, Tax has also been found to accumulate in the cytoplasm. The results contained herein begin to characterize the process of Tax secretion from the cell. Specifically, cytoplasmic Tax was demonstrated to localize to organelles associated with the cellular secretory process including the endoplasmic reticulum and Golgi complex. Additionally, it was demonstrated that full-length Tax was secreted from both baby hamster kidney cells and a human kidney tumor cell line, suggesting that Tax enters the secretory pathway in a leaderless manner. Tax secretion was partially inhibited by brefeldin A, suggesting that Tax migrated from the endoplasmic reticulum to the Golgi complex. In addition, combined treatment of Tax-transfected BHK-21 cells with phorbol myristate acetate and ionomycin resulted in a small increase in the amount of Tax secreted, suggesting that a fraction of cytoplasmic Tax was present in the regulated secretory pathway. These studies begin to provide a link between Tax localization to the cytoplasm, the detection of Tax in the extracellular environment, its possible role as an extracellular effector molecule, and a potential role in neurodegenerative disease associated with HTLV-I infection.
MeSH term(s)	Animals ; Apoptosis ; Bacterial Proteins/metabolism ; Brefeldin A/pharmacology ; Cell Culture Techniques ; Cell Line ; Cell Line, Tumor ; Central Nervous System/embryology ; Cricetinae ; Culture Media ; Cytoplasm/metabolism ; DNA, Complementary/metabolism ; Endoplasmic Reticulum/metabolism ; Enzyme-Linked Immunosorbent Assay ; Gene Products, tax/metabolism ; Golgi Apparatus/metabolism ; Green Fluorescent Proteins/metabolism ; Humans ; Interleukin-6/metabolism ; Ionomycin/pharmacology ; Luminescent Proteins/metabolism ; Models, Biological ; Necrosis ; Neurodegenerative Diseases/metabolism ; Neurons/metabolism ; Plasmids/metabolism ; Protein Structure, Tertiary ; Tetradecanoylphorbol Acetate/pharmacology ; Time Factors ; Transcription, Genetic ; Transcriptional Activation ; Transfection
Chemical Substances	Bacterial Proteins ; Culture Media ; Cyan Fluorescent Protein ; DNA, Complementary ; Gene Products, tax ; Interleukin-6 ; Luminescent Proteins ; yellow fluorescent protein, Bacteria ; Green Fluorescent Proteins (147336-22-9) ; Brefeldin A (20350-15-6) ; Ionomycin (56092-81-0) ; Tetradecanoylphorbol Acetate (NI40JAQ945)
Language	English
Publishing date	2005-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M409851200
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.108: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Characterization of a nuclear export signal within the human T cell leukemia virus type I transactivator protein Tax.

Alefantis, Timothy / Barmak, Kate / Harhaj, Edward W / Grant, Christian / Wigdahl, Brian

The Journal of biological chemistry

2003 Volume 278, Issue 24, Page(s) 21814–21822

Abstract: Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. The HTLV-I transactivator protein Tax plays an integral role in the etiology of adult T cell ... ...

Abstract	Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. The HTLV-I transactivator protein Tax plays an integral role in the etiology of adult T cell leukemia, as expression of Tax in T lymphocytes has been shown to result in immortalization. In addition, Tax is known to interface with numerous transcription factor families, including activating transcription factor/cAMP response element-binding protein and nuclear factor-kappaB, requiring Tax to localize to both the nucleus and cytoplasm. In this report, the nucleocytoplasmic localization of Tax was examined in Jurkat, HeLa, and U-87 MG cells. The results reported herein indicate that Tax contains a leucine-rich nuclear export signal (NES) that, when fused to green fluorescent protein (GFP), can direct nuclear export via the CRM-1 pathway, as determined by leptomycin B inhibition of nuclear export. However, cytoplasmic localization of full-length Tax was not altered by treatment with leptomycin B, suggesting that native Tax utilizes another nuclear export pathway. Additional support for the presence of a functional NES has also been shown because the NES mutant Tax(L200A)-GFP localized to the nuclear membrane in the majority of U-87 MG cells. Evidence has also been provided suggesting that the Tax NES likely exists as a conditionally masked signal because the truncation mutant TaxDelta214-GFP localized constitutively to the cytoplasm. These results suggest that Tax localization may be directed by specific changes in Tax conformation or by specific interactions with cellular proteins leading to changes in the availability of the Tax NES and nuclear localization signal.
MeSH term(s)	Active Transport, Cell Nucleus ; Amino Acid Sequence ; Blotting, Western ; Cell Line ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Dimerization ; Fatty Acids, Unsaturated/pharmacology ; Gene Products, tax/metabolism ; Green Fluorescent Proteins ; HeLa Cells ; Humans ; Jurkat Cells ; Leucine/metabolism ; Luminescent Proteins/metabolism ; Microscopy, Fluorescence ; Models, Biological ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutation ; NF-kappa B/metabolism ; Plasmids/metabolism ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/metabolism ; Transcriptional Activation ; Transfection
Chemical Substances	Fatty Acids, Unsaturated ; Gene Products, tax ; Luminescent Proteins ; NF-kappa B ; Recombinant Fusion Proteins ; Green Fluorescent Proteins (147336-22-9) ; Leucine (GMW67QNF9C) ; leptomycin B (Y031I2N1EO)
Language	English
Publishing date	2003-04-01
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M211576200
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.108: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito