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1.
Divers Distrib ; 26(12): 1780-1797, 2020 Dec.
Article in English | MEDLINE | ID: mdl-36960319

ABSTRACT

Aim: The introduction of aquatic non-indigenous species (ANS) has become a major driver for global changes in species biogeography. We examined spatial patterns and temporal trends of ANS detections since 1965 to inform conservation policy and management. Location: Global. Methods: We assembled an extensive dataset of first records of detection of ANS (1965-2015) across 49 aquatic ecosystems, including the (a) year of first collection, (b) population status and (c) potential pathway(s) of introduction. Data were analysed at global and regional levels to assess patterns of detection rate, richness and transport pathways. Results: An annual mean of 43 (±16 SD) primary detections of ANS occurred-one new detection every 8.4 days for 50 years. The global rate of detections was relatively stable during 1965-1995, but increased rapidly after this time, peaking at roughly 66 primary detections per year during 2005-2010 and then declining marginally. Detection rates were variable within and across regions through time. Arthropods, molluscs and fishes were the most frequently reported ANS. Most ANS were likely introduced as stowaways in ships' ballast water or biofouling, although direct evidence is typically absent. Main conclusions: This synthesis highlights the magnitude of recent ANS detections, yet almost certainly represents an underestimate as many ANS go unreported due to limited search effort and diminishing taxonomic expertise. Temporal rates of detection are also confounded by reporting lags, likely contributing to the lower detection rate observed in recent years. There is a critical need to implement standardized, repeated methods across regions and taxa to improve the quality of global-scale comparisons and sustain core measures over longer time-scales. It will be fundamental to fill in knowledge gaps given that invasion data representing broad regions of the world's oceans are not yet readily available and to maintain knowledge pipelines for adaptive management.

2.
Glob Chang Biol ; 25(1): 25-38, 2019 01.
Article in English | MEDLINE | ID: mdl-30295388

ABSTRACT

Climate change and increased anthropogenic activities are expected to elevate the potential of introducing nonindigenous species (NIS) into the Arctic. Yet, the knowledge base needed to identify gaps and priorities for NIS research and management is limited. Here, we reviewed primary introduction events to each ecoregion of the marine Arctic realm to identify temporal and spatial patterns, likely source regions of NIS, and the putative introduction pathways. We included 54 introduction events representing 34 unique NIS. The rate of NIS discovery ranged from zero to four species per year between 1960 and 2015. The Iceland Shelf had the greatest number of introduction events (n = 14), followed by the Barents Sea (n = 11), and the Norwegian Sea (n = 11). Sixteen of the 54 introduction records had no known origins. The majority of those with known source regions were attributed to the Northeast Atlantic and the Northwest Pacific, 19 and 14 records, respectively. Some introduction events were attributed to multiple possible pathways. For these introductions, vessels transferred the greatest number of aquatic NIS (39%) to the Arctic, followed by natural spread (30%) and aquaculture activities (25%). Similar trends were found for introductions attributed to a single pathway. The phyla Arthropoda and Ochrophyta had the highest number of recorded introduction events, with 19 and 12 records, respectively. Recommendations including vector management, horizon scanning, early detection, rapid response, and a pan-Arctic biodiversity inventory are considered in this paper. Our study provides a comprehensive record of primary introductions of NIS for marine environments in the circumpolar Arctic and identifies knowledge gaps and opportunities for NIS research and management. Ecosystems worldwide will face dramatic changes in the coming decades due to global change. Our findings contribute to the knowledge base needed to address two aspects of global change-invasive species and climate change.


Subject(s)
Aquatic Organisms/physiology , Climate Change , Introduced Species/trends , Animals , Arctic Regions , Biodiversity , Ecosystem , Introduced Species/statistics & numerical data , Risk
3.
Glob Chang Biol ; 24(6): 2708-2720, 2018 06.
Article in English | MEDLINE | ID: mdl-29330969

ABSTRACT

Invasions of freshwater habitats by marine and brackish species have become more frequent in recent years with many of those species originating from the Ponto-Caspian region. Populations of Ponto-Caspian species have successfully established in the North and Baltic Seas and their adjoining rivers, as well as in the Great Lakes-St. Lawrence River region. To determine if Ponto-Caspian taxa more readily acclimatize to and colonize diverse salinity habitats than taxa from other regions, we conducted laboratory experiments on 22 populations of eight gammarid species native to the Ponto-Caspian, Northern European and Great Lakes-St. Lawrence River regions. In addition, we conducted a literature search to survey salinity ranges of these species worldwide. Finally, to explore evolutionary relationships among examined species and their populations, we sequenced the mitochondrial cytochrome c oxidase subunit I gene (COI) from individuals used for our experiments. Our study revealed that all tested populations tolerate wide ranges of salinity, however, different patterns arose among species from different regions. Ponto-Caspian taxa showed lower mortality in fresh water, while Northern European taxa showed lower mortality in fully marine conditions. Genetic analyses showed evolutionary divergence among species from different regions. Due to the geological history of the two regions, as well as high tolerance of Ponto-Caspian species to fresh water, whereas Northern European species are more tolerant of fully marine conditions, we suggest that species originating from the Ponto-Caspian and Northern European regions may be adapted to freshwater and marine environments, respectively. Consequently, the perception that Ponto-Caspian species are more successful colonizers might be biased by the fact that areas with highest introduction frequency of NIS (i.e., shipping ports) are environmentally variable habitats which often include freshwater conditions that cannot be tolerated by euryhaline taxa of marine origin.


Subject(s)
Amphipoda/physiology , Biological Evolution , Introduced Species , Salt Tolerance , Animals , Arthropod Proteins/genetics , Canada , Electron Transport Complex IV/genetics , Europe , Evolution, Molecular , Mitochondrial Proteins/genetics , United States
4.
Front Ecol Environ ; 16(6): 345-353, 2018.
Article in English | MEDLINE | ID: mdl-31942166

ABSTRACT

Biological invasions are largely considered to be a "numbers game", wherein the larger the introduction effort, the greater the probability that an introduced population will become established. However, conditions during transport - an early stage of the invasion - can be particularly harsh, thereby greatly reducing the size of a population available to establish in a new region. Some successful non-indigenous species are more tolerant of environmental and anthropogenic stressors than related native species, possibly stemming from selection (ie survival of only pre-adapted individuals for particular environmental conditions) during the invasion process. By reviewing current literature concerning population genetics and consequences of selection on population fitness, we propose that selection acting on transported populations can facilitate local adaptation, which may result in a greater likelihood of invasion than predicted by propagule pressure alone. Specifically, we suggest that detailed surveys should be conducted to determine interactions between molecular mechanisms and demographic factors, given that current management strategies may underestimate invasion risk.

6.
Mar Biol ; 164(6): 121, 2017.
Article in English | MEDLINE | ID: mdl-28579642

ABSTRACT

The Topical Collection on Invasive Species includes 50 articles addressing many tenets of marine invasion ecology. The collection covers important topics relating to propagule pressure associated with transport vectors, species characteristics, attributes of recipient ecosystems, invasion genetics, biotic interactions, testing of invasion hypotheses, invasion dynamics and spread, and impacts of nonindigenous species. This article summarizes some of the collection's highlights.

7.
Mar Biol ; 163(12): 250, 2016.
Article in English | MEDLINE | ID: mdl-27980347

ABSTRACT

Human-mediated vectors often inadvertently translocate species assemblages to new environments. Examining the dynamics of entrained species assemblages during transport can provide insights into the introduction risk associated with these vectors. Ship biofouling is a major transport vector of nonindigenous species in coastal ecosystems globally, yet its magnitude in the Arctic is poorly understood. To determine whether biofouling organisms on ships can survive passages in Arctic waters, we examined how biofouling assemblage structure changed before, during, and after eight round-trip military voyages from temperate to Arctic ports in Canada. Species richness first decreased (~70% loss) and then recovered (~27% loss compared to the original assemblages), as ships travelled to and from the Arctic, respectively, whereas total abundance typically declined over time (~55% total loss). Biofouling community structure differed significantly before and during Arctic transits as well as between those sampled during and after voyages. Assemblage structure varied across different parts of the hull; however, temporal changes were independent of hull location, suggesting that niche areas did not provide protection for biofouling organisms against adverse conditions in the Arctic. Biofouling algae appear to be more tolerant of transport conditions during Arctic voyages than are mobile, sessile, and sedentary invertebrates. Our results suggest that biofouling assemblages on ships generally have poor survivorship during Arctic voyages. Nonetheless, some potential for transporting nonindigenous species to the Arctic via ship biofouling remains, as at least six taxa new to the Canadian Arctic, including a nonindigenous cirripede, appeared to have survived transits from temperate to Arctic ports.

8.
PLoS One ; 10(3): e0118267, 2015.
Article in English | MEDLINE | ID: mdl-25763859

ABSTRACT

Understanding the implications of different management strategies is necessary to identify best conservation trajectories for ecosystems exposed to anthropogenic stressors. For example, science-based risk assessments at large scales are needed to understand efficacy of different vector management approaches aimed at preventing biological invasions associated with commercial shipping. We conducted a landscape-scale analysis to examine the relative invasion risk of ballast water discharges among different shipping pathways (e.g., Transoceanic, Coastal or Domestic), ecosystems (e.g., freshwater, brackish and marine), and timescales (annual and per discharge event) under current and future management regimes. The arrival and survival potential of nonindigenous species (NIS) was estimated based on directional shipping networks and their associated propagule pressure, environmental similarity between donor-recipient ecosystems (based on salinity and temperature), and effects of current and future management strategies (i.e., ballast water exchange and treatment to meet proposed international biological discharge standards). Our findings show that current requirements for ballast water exchange effectively reduce invasion risk to freshwater ecosystems but are less protective of marine ecosystems because of greater environmental mismatch between source (oceanic) and recipient (freshwater) ecoregions. Future requirements for ballast water treatment are expected to reduce risk of zooplankton NIS introductions across ecosystem types but are expected to be less effective in reducing risk of phytoplankton NIS. This large-scale risk assessment across heterogeneous ecosystems represents a major step towards understanding the likelihood of invasion in relation to shipping networks, the relative efficacy of different invasion management regimes and seizing opportunities to reduce the ecological and economic implications of biological invasions.


Subject(s)
Fresh Water , Plankton , Seawater , Waste Disposal, Fluid/methods , Waste Disposal, Fluid/standards , Animals , Canada , Introduced Species , Phytoplankton , Risk Assessment , Salinity , Water Pollutants , Water Purification
9.
Proc Biol Sci ; 282(1799): 20141517, 2015 Jan 22.
Article in English | MEDLINE | ID: mdl-25473007

ABSTRACT

Mixed-species assemblages are often unintentionally introduced into new ecosystems. Analysing how assemblage structure varies during transport may provide insights into how introduction risk changes before propagules are released. Characterization of introduction risk is typically based on assessments of colonization pressure (CP, the number of species transported) and total propagule pressure (total PP, the total abundance of propagules released) associated with an invasion vector. Generally, invasion potential following introduction increases with greater CP or total PP. Here, we extend these assessments using rank-abundance distributions to examine how CP : total PP relationships change temporally in ballast water of ocean-going ships. Rank-abundance distributions and CP : total PP patterns varied widely between trans-Atlantic and trans-Pacific voyages, with the latter appearing to pose a much lower risk than the former. Responses also differed by taxonomic group, with invertebrates experiencing losses mainly in total PP, while diatoms and dinoflagellates sustained losses mainly in CP. In certain cases, open-ocean ballast water exchange appeared to increase introduction risk by uptake of new species or supplementation of existing ones. Our study demonstrates that rank-abundance distributions provide new insights into the utility of CP and PP in characterizing introduction risk.


Subject(s)
Animal Distribution , Aquatic Organisms , Introduced Species , Animals , Ecosystem , Linear Models , Models, Theoretical , Population Density , Risk , Seawater , Ships
10.
Immunity ; 8(4): 473-82, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9586637

ABSTRACT

The vaccinia virus A39R protein is a member of the semaphorin family. A39R.Fc protein was used to affinity purify an A39R receptor from a human B cell line. Tandem mass spectrometry of receptor peptides yielded partial amino acid sequences that allowed the identification of corresponding cDNA clones. Sequence analysis of this receptor indicated that it is a novel member of the plexin family and identified a semaphorin-like domain within this family, thus suggesting an evolutionary relationship between receptor and ligand. A39R up-regulated ICAM-1 on, and induced cytokine production from, human monocytes. These data, then, describe a receptor for an immunologically active semaphorin and suggest that it may serve as a prototype for other plexin-semaphorin binding pairs.


Subject(s)
Cytokines/biosynthesis , Membrane Proteins/physiology , Monocytes/immunology , Receptors, Cell Surface/metabolism , Receptors, Virus , Vaccinia virus/immunology , Viral Proteins/immunology , Viral Proteins/metabolism , Amino Acid Sequence , B-Lymphocytes/metabolism , Cell Adhesion Molecules/genetics , Cell Line , Cloning, Molecular , Evolution, Molecular , Humans , Intercellular Adhesion Molecule-1/metabolism , Ligands , Membrane Proteins/chemistry , Membrane Proteins/genetics , Molecular Sequence Data , Monocytes/metabolism , Nerve Tissue Proteins/genetics , Receptors, Cell Surface/genetics , Receptors, Cell Surface/isolation & purification , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Recombinant Proteins/metabolism , Sequence Homology, Amino Acid , Tissue Distribution , Vaccinia virus/genetics , Viral Proteins/genetics
11.
J Virol ; 72(5): 4015-21, 1998 May.
Article in English | MEDLINE | ID: mdl-9557689

ABSTRACT

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus associated with infectious mononucleosis and several tumors. The BARF1 gene is transcribed early after EBV infection from the BamHI A fragment of the EBV genome. Evidence shown here indicates that the BARF1 protein is secreted into the medium of transfected cells and from EBV-carrying B cells induced to allow lytic replication of the virus. Expression cloning identified colony-stimulating factor-1 (CSF-1) as a ligand for BARF1. Computer-assisted analyses indicated that subtle amino acid sequence homology exists between BARF1 and c-fins, the cellular proto-oncogene that is the receptor for CSF-1. Recombinant BARF1 protein was found to be biologically active, and it neutralized the proliferative effects of human CSF-1 in a dose-dependent fashion when assayed in vitro. Since CSF-1 is a pleiotropic cytokine best known for its differentiating effects on macrophages, these data suggest that BARF1 may function to modulate the host immune response to EBV infection.


Subject(s)
Herpesvirus 4, Human/genetics , Macrophage Colony-Stimulating Factor/metabolism , Receptor, Macrophage Colony-Stimulating Factor/genetics , Viral Proteins/genetics , Animals , COS Cells , Cell Line , Chlorocebus aethiops , Genes, Viral , Herpesvirus 4, Human/metabolism , Humans , Ligands , Macrophage Colony-Stimulating Factor/genetics , Proto-Oncogene Mas , Receptor, Macrophage Colony-Stimulating Factor/metabolism , Sequence Homology, Amino Acid , Solubility , Viral Proteins/metabolism
12.
J Virol ; 70(8): 5557-63, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8764069

ABSTRACT

The Epstein-Barr virus BZLF2 gene encodes a glycoprotein that associates with gH and gL and facilitates the infection of B lymphocytes. In order to determine whether the BZLF2 protein recognizes a B-cell-specific surface antigen, a soluble protein containing the extracellular portion of the BZLF2 protein linked to the Fc portion of human immunoglobulin G1 (BZLF2.Fc) was expressed from mammalian cells. BZLF2.Fc was used in an expression cloning system and found to bind to a beta-chain allele of the HLA-DR locus of the class II major histocompatibility complex (MHC). Analysis of amino- and carboxy-terminal deletion mutants of the BZLF2.Fc protein indicated that the first 90 amino acids of BZLF2.Fc are not required for HLA-DR beta-chain recognition. Site-directed mutagenesis of an HLA-DR beta-chain cDNA and subsequent immunoprecipitation of expressed mutant beta-chain proteins using BZLF2.Fc indicated that the beta1 domain, which participates in the formation of peptide binding pockets, is required for BZLF2.Fc recognition. The addition of BZLF2.Fc to sensitized peripheral blood mononuclear cells in vitro abolished their proliferative response to antigen and inhibited cytokine-dependent cytotoxic T-cell generation in mixed lymphocyte cultures. Flow-cytometric analysis of Akata cells induced to express late Epstein-Barr virus antigens indicated that expression of BZLF2 did not result in reduced surface expression levels of MHC class II. The ability of BZLF2.Fc to bind to the HLA-DR beta chain suggests that the BZLF2 protein may interact with MHC class II on the surfaces of B cells.


Subject(s)
Glycoproteins , HLA-DR Antigens/immunology , Herpesviridae Infections/immunology , Herpesvirus 4, Human/immunology , Lymphocytes/virology , Tumor Virus Infections/immunology , Viral Proteins/immunology , Amino Acid Sequence , Antigen Presentation , Cell Line , Herpesviridae Infections/virology , Humans , Lymphocytes/immunology , Molecular Sequence Data , Protein Binding , Tumor Virus Infections/virology , Viral Proteins/genetics
13.
J Neurol Neurosurg Psychiatry ; 57(10): 1258-9, 1994 Oct.
Article in English | MEDLINE | ID: mdl-7931392

ABSTRACT

Despite successful orthoptic liver transplantation some patients develop a recurrent headache that interferes with their quality of life. To estimate the frequency of this symptom 34 patients who had undergone orthoptic liver transplantation were questioned about the history and character of any headache. Six patients described a recurrent headache typical of migraine only since transplantation. In two patients the pain improved after reduction of cyclosporin dosage and thereby plasma cyclosporin concentration.


Subject(s)
Cyclosporine/adverse effects , Headache/chemically induced , Female , Humans , Liver Transplantation , Male , Middle Aged
14.
EMBO J ; 13(16): 3757-62, 1994 Aug 15.
Article in English | MEDLINE | ID: mdl-8070404

ABSTRACT

A family of tyrosine kinase receptors related to the product of the eph gene has been described recently. One of these receptors, elk, has been shown to be expressed only in brain and testes. Using a direct expression cloning technique, a ligand for the elk receptor has been isolated by screening a human placenta cDNA library with a fusion protein containing the extracellular domain of the receptor. This isolated cDNA encodes a transmembrane protein. While the sequence of the ligand cDNA is unique, it is related to a previously described sequence known as B61. Northern blot analysis of human tissue mRNA showed that the elk ligand's mRNA is 3.5 kb long and is found in placenta, heart, lung, liver, skeletal muscle, kidney and pancreas. Southern blot analysis showed that the gene is highly conserved in a wide variety of species. Both elk ligand and B61 mRNAs are inducible by tumour necrosis factor in human umbilical vein endothelial cells. In addition, both proteins show promiscuity in binding to the elk and the related hek receptors. Since these two ligand sequences are similar, and since elk and hek are members of a larger family of eph-related receptor molecules, we refer to these ligands as LERKs (ligands for eph-related kinases).


Subject(s)
DNA-Binding Proteins , Proteins/genetics , Proteins/metabolism , Proto-Oncogene Proteins , Receptor Protein-Tyrosine Kinases/metabolism , Retroviridae Proteins, Oncogenic/metabolism , Transcription Factors , Amino Acid Sequence , Base Sequence , Endothelium, Vascular/physiology , Ephrin-A1 , Ephrin-B1 , Gene Expression Regulation/drug effects , Humans , Molecular Sequence Data , Multigene Family/genetics , Protein Binding , RNA, Messenger/analysis , Receptor Protein-Tyrosine Kinases/genetics , Receptor, EphA3 , Recombinant Fusion Proteins/metabolism , Retroviridae Proteins, Oncogenic/genetics , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Species Specificity , Tissue Distribution , Tumor Necrosis Factor-alpha/pharmacology , Umbilical Veins/physiology , ets-Domain Protein Elk-1
16.
Eur J Immunol ; 23(7): 1643-8, 1993 Jul.
Article in English | MEDLINE | ID: mdl-8100776

ABSTRACT

CD69 is a disulfide-linked homo-dimer expressed on the surface of activated T cells, B cells, natural killer cells, neutrophils and platelets. Antibody crosslinking of CD69 in the presence of phorbol ester results in cellular activation events including proliferation and the induction of specific genes. Using an expression cloning strategy we have isolated cDNA encoding human CD69 from a CD4+ T cell clone. Transfection of the cDNA clone in CV-1/EBNA cells results in the expression of a covalently linked homodimer. The cDNA insert hybridizes to a 1.7-kb mRNA in phorbol 12-myristate 13-acetate- or phytohemoagglutinin-stimulated human T cells. Using the human clone we have isolated cDNA encoding mouse CD69, which, when expressed in human T cells allowed those cells to respond to anti-mouse CD69 antibodies by secreting interleukin-2 and interferon-gamma. Sequence analysis showed that both mouse and human CD69 are type II membrane glycoproteins related to the NKR-P1 and Ly-49 families of natural killer cell activation molecules.


Subject(s)
Antigens, CD/chemistry , Antigens, Differentiation, T-Lymphocyte/chemistry , CD4-Positive T-Lymphocytes/chemistry , Lymphocyte Activation , Membrane Glycoproteins/chemistry , Amino Acid Sequence , Animals , Base Sequence , Cloning, Molecular , DNA , Humans , Killer Cells, Natural/chemistry , Lectins, C-Type , Mice , Molecular Sequence Data , Sequence Alignment
17.
Cell ; 73(7): 1349-60, 1993 Jul 02.
Article in English | MEDLINE | ID: mdl-8391931

ABSTRACT

CD30 is a surface marker for neoplastic cells of Hodgkin's lymphoma and shows sequence homology to members of the tumor necrosis factor (TNF) receptor superfamily. Using a chimeric probe consisting of the extracellular domain of CD30 fused to truncated immunoglobulin heavy chains, we expression cloned the cDNA cognate from the murine T cell clone 7B9. The encoded protein is a 239 amino acid type II membrane protein whose C-terminal domain shows significant homology to TNF alpha, TNF beta, and the CD40L. Cross-hybridization to an induced peripheral blood T cell cDNA library yielded the human homolog, which is 72% identical at the amino acid level. The recombinant human ligand enhances the proliferation of CD3-activated T cells yet induces differential responses, including cell death, in several CD30+ lymphoma-derived clones. The human and murine genes map to 9q33 and the proximal region of chromosome 4, respectively.


Subject(s)
Antigens, CD/metabolism , Antigens, Neoplasm/metabolism , Cytokines/genetics , Hodgkin Disease/metabolism , Membrane Glycoproteins/genetics , Tumor Necrosis Factor-alpha/genetics , Amino Acid Sequence , Animals , Base Sequence , Binding, Competitive , Biomarkers, Tumor/metabolism , CD30 Ligand , Chromosome Mapping , Cytokines/chemistry , Hodgkin Disease/immunology , Humans , Ki-1 Antigen , Ligands , Membrane Glycoproteins/chemistry , Mice , Mice, Inbred C57BL , Molecular Sequence Data , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid , Tumor Necrosis Factor-alpha/chemistry
19.
Proc Natl Acad Sci U S A ; 88(13): 5809-13, 1991 Jul 01.
Article in English | MEDLINE | ID: mdl-1829529

ABSTRACT

Granulocyte/macrophage colony-stimulating factor-interleukin 3 (GM-CSF-IL-3) fusion proteins were generated by construction of a plasmid in which the coding regions of human GM-CSF and IL-3 cDNAs were connected by a synthetic linker sequence followed by subsequent expression in yeast. Both GM-CSF-IL-3 and IL-3-GM-CSF fusion proteins were purified to homogeneity and shown to bind to cell-surface receptors through either their GM-CSF or IL-3 domains. The fusion proteins exhibited enhanced receptor affinity, proliferative activity, and hematopoietic colony-stimulating activity compared with either IL-3 and/or GM-CSF alone. This suggests that GM-CSF-IL-3 fusion proteins may hold future promise as therapeutic agents.


Subject(s)
Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage , Hematopoiesis/drug effects , Interleukin-3/administration & dosage , Recombinant Fusion Proteins/pharmacology , Base Sequence , Binding, Competitive , Cloning, Molecular , Colony-Forming Units Assay , Dose-Response Relationship, Drug , Granulocyte-Macrophage Colony-Stimulating Factor/chemistry , Humans , In Vitro Techniques , Interleukin-3/chemistry , Molecular Sequence Data , Oligonucleotides/chemistry , Protein Conformation , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Receptors, Interleukin-3/metabolism , Recombinant Fusion Proteins/chemistry
20.
Biochem Biophys Res Commun ; 176(1): 335-42, 1991 Apr 15.
Article in English | MEDLINE | ID: mdl-1850261

ABSTRACT

A transcriptionally active open reading frame (T2) from Shope Fibroma Virus was recently shown to have striking sequence homology with members of a new superfamily of cell surface proteins, including a receptor for human tumor necrosis factor. Here we report that recombinant T2 protein expressed in COS cells is a soluble, secreted glycoprotein which specifically binds human TNF alpha and beta, and inhibits binding of these cytokines to native TNF receptors on cells. T2 binding of TNF is not inhibited by nerve growth factor, although the nerve growth factor receptor is also a member of the same family, nor by nine other recombinant cytokines. Further, the repeating domain structure of T2 most closely resembles that of the type I TNF receptor (p75) and is significantly different from other family members, including the type II TNF receptor (p55). Since T2 possesses a leader sequence but lacks a transmembrane domain, these results confirm the original suggestion (1) that T2 represents a soluble form of the type I TNF receptor which is secreted from virally infected cells, and whose function is to immunosuppress the host by abrogating the potentially destructive effects of TNF. This is the first such virally-encoded soluble cytokine receptor to be identified, and may represent a more general mechanism by which viruses subvert the host immune system.


Subject(s)
Fibroma Virus, Rabbit/genetics , Genes, Viral , Multigene Family , Open Reading Frames , Receptors, Cell Surface/genetics , Tumor Necrosis Factor-alpha/metabolism , Amino Acid Sequence , Animals , Cell Line , Humans , Molecular Sequence Data , Oligonucleotide Probes , Protein Biosynthesis , Receptors, Cell Surface/metabolism , Receptors, Tumor Necrosis Factor , Recombinant Proteins/metabolism , Repetitive Sequences, Nucleic Acid , Sequence Homology, Nucleic Acid , Transfection
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