Redirecting coronavirus to a nonnative receptor through a virus-encoded targeting adapter.
Identifieur interne : 003D49 ( Main/Exploration ); précédent : 003D48; suivant : 003D50Redirecting coronavirus to a nonnative receptor through a virus-encoded targeting adapter.
Auteurs : M H Verheije [Pays-Bas] ; T. Würdinger ; V W Van Beusechem ; C A M. De Haan ; W R Gerritsen ; P J M. RottierSource :
- Journal of virology [ 0022-538X ] ; 2006.
Descripteurs français
- KwdFr :
- ADN recombiné (génétique), Animaux, Antigène carcinoembryonnaire (génétique), Antigène carcinoembryonnaire (physiologie), Chats, Fusion membranaire, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (génétique), Glycoprotéines membranaires (physiologie), Humains, Lignée cellulaire, Produits du gène vif (génétique), Produits du gène vif (physiologie), Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (physiologie), Protéines recombinantes (génétique), Protéines recombinantes (métabolisme), Récepteurs viraux (génétique), Récepteurs viraux (physiologie), Réplication virale, Sites de fixation, Souris, Séquence nucléotidique, Virus de l'hépatite murine (génétique), Virus de l'hépatite murine (pathogénicité), Virus de l'hépatite murine (physiologie).
- MESH :
- génétique : ADN recombiné, Antigène carcinoembryonnaire, Glycoprotéines membranaires, Produits du gène vif, Protéines de l'enveloppe virale, Protéines recombinantes, Récepteurs viraux, Virus de l'hépatite murine.
- métabolisme : Protéines recombinantes.
- pathogénicité : Virus de l'hépatite murine.
- physiologie : Antigène carcinoembryonnaire, Glycoprotéines membranaires, Produits du gène vif, Protéines de l'enveloppe virale, Récepteurs viraux, Virus de l'hépatite murine.
- Animaux, Chats, Fusion membranaire, Glycoprotéine de spicule des coronavirus, Humains, Lignée cellulaire, Réplication virale, Sites de fixation, Souris, Séquence nucléotidique.
English descriptors
- KwdEn :
- Animals, Base Sequence, Binding Sites, Carcinoembryonic Antigen (genetics), Carcinoembryonic Antigen (physiology), Cats, Cell Line, DNA, Recombinant (genetics), Gene Products, vif (genetics), Gene Products, vif (physiology), Humans, Membrane Fusion, Membrane Glycoproteins (genetics), Membrane Glycoproteins (physiology), Mice, Murine hepatitis virus (genetics), Murine hepatitis virus (pathogenicity), Murine hepatitis virus (physiology), Receptors, Virus (genetics), Receptors, Virus (physiology), Recombinant Proteins (genetics), Recombinant Proteins (metabolism), Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (genetics), Viral Envelope Proteins (physiology), Virus Replication.
- MESH :
- chemical , genetics : Carcinoembryonic Antigen, DNA, Recombinant, Gene Products, vif, Membrane Glycoproteins, Receptors, Virus, Recombinant Proteins, Viral Envelope Proteins.
- chemical , metabolism : Recombinant Proteins.
- chemical , physiology : Carcinoembryonic Antigen, Gene Products, vif, Membrane Glycoproteins, Receptors, Virus, Viral Envelope Proteins.
- genetics : Murine hepatitis virus.
- pathogenicity : Murine hepatitis virus.
- physiology : Murine hepatitis virus.
- Animals, Base Sequence, Binding Sites, Cats, Cell Line, Humans, Membrane Fusion, Mice, Spike Glycoprotein, Coronavirus, Virus Replication.
Abstract
Murine hepatitis coronavirus (MHV)-A59 infection depends on the interaction of its spike (S) protein with the cellular receptor mCEACAM1a present on murine cells. Human cells lack this receptor and are therefore not susceptible to MHV. Specific alleviation of the tropism barrier by redirecting MHV to a tumor-specific receptor could lead to a virus with appealing properties for tumor therapy. To demonstrate that MHV can be retargeted to a nonnative receptor on human cells, we produced bispecific adapter proteins composed of the N-terminal D1 domain of mCEACAM1a linked to a short targeting peptide, the six-amino-acid His tag. Preincubation of MHV with the adapter proteins and subsequent inoculation of human cells expressing an artificial His receptor resulted in infection of these otherwise nonsusceptible cells and led to subsequent production of progeny virus. To generate a self-targeted virus able to establish multiround infection of the target cells, we subsequently incorporated the gene encoding the bispecific adapter protein as an additional expression cassette into the MHV genome through targeted RNA recombination. When inoculated onto murine LR7 cells, the resulting recombinant virus indeed expressed the adapter protein. Furthermore, inoculation of human target cells with the virus resulted in a His receptor-specific infection that was multiround. Extensive cell-cell fusion and rapid cell killing of infected target cells was observed. Our results show that MHV can be genetically redirected via adapters composed of the S protein binding part of mCEACAM1a and a targeting peptide recognizing a nonnative receptor expressed on human cells, consequently leading to rapid cell death. The results provide interesting leads for further investigations of the use of coronaviruses as antitumor agents.
DOI: 10.1128/JVI.80.3.1250-1260.2006
PubMed: 16415002
Affiliations:
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Le document en format XML
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Würdinger</name></author><author><name sortKey="Van Beusechem, V W" sort="Van Beusechem, V W" uniqKey="Van Beusechem V" first="V W" last="Van Beusechem">V W Van Beusechem</name></author><author><name sortKey="De Haan, C A M" sort="De Haan, C A M" uniqKey="De Haan C" first="C A M" last="De Haan">C A M. De Haan</name></author><author><name sortKey="Gerritsen, W R" sort="Gerritsen, W R" uniqKey="Gerritsen W" first="W R" last="Gerritsen">W R Gerritsen</name></author><author><name sortKey="Rottier, P J M" sort="Rottier, P J M" uniqKey="Rottier P" first="P J M" last="Rottier">P J M. 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Würdinger</name></author><author><name sortKey="Van Beusechem, V W" sort="Van Beusechem, V W" uniqKey="Van Beusechem V" first="V W" last="Van Beusechem">V W Van Beusechem</name></author><author><name sortKey="De Haan, C A M" sort="De Haan, C A M" uniqKey="De Haan C" first="C A M" last="De Haan">C A M. De Haan</name></author><author><name sortKey="Gerritsen, W R" sort="Gerritsen, W R" uniqKey="Gerritsen W" first="W R" last="Gerritsen">W R Gerritsen</name></author><author><name sortKey="Rottier, P J M" sort="Rottier, P J M" uniqKey="Rottier P" first="P J M" last="Rottier">P J M. Rottier</name></author></analytic><series><title level="j">Journal of virology</title><idno type="ISSN">0022-538X</idno><imprint><date when="2006" type="published">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Base Sequence</term><term>Binding Sites</term><term>Carcinoembryonic Antigen (genetics)</term><term>Carcinoembryonic Antigen (physiology)</term><term>Cats</term><term>Cell Line</term><term>DNA, Recombinant (genetics)</term><term>Gene Products, vif (genetics)</term><term>Gene Products, vif (physiology)</term><term>Humans</term><term>Membrane Fusion</term><term>Membrane Glycoproteins (genetics)</term><term>Membrane Glycoproteins (physiology)</term><term>Mice</term><term>Murine hepatitis virus (genetics)</term><term>Murine hepatitis virus (pathogenicity)</term><term>Murine hepatitis virus (physiology)</term><term>Receptors, Virus (genetics)</term><term>Receptors, Virus (physiology)</term><term>Recombinant Proteins (genetics)</term><term>Recombinant Proteins (metabolism)</term><term>Spike Glycoprotein, Coronavirus</term><term>Viral Envelope Proteins (genetics)</term><term>Viral Envelope Proteins (physiology)</term><term>Virus Replication</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN recombiné (génétique)</term><term>Animaux</term><term>Antigène carcinoembryonnaire (génétique)</term><term>Antigène carcinoembryonnaire (physiologie)</term><term>Chats</term><term>Fusion membranaire</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires (génétique)</term><term>Glycoprotéines membranaires (physiologie)</term><term>Humains</term><term>Lignée cellulaire</term><term>Produits du gène vif (génétique)</term><term>Produits du gène vif (physiologie)</term><term>Protéines de l'enveloppe virale (génétique)</term><term>Protéines de l'enveloppe virale (physiologie)</term><term>Protéines recombinantes (génétique)</term><term>Protéines recombinantes (métabolisme)</term><term>Récepteurs viraux (génétique)</term><term>Récepteurs viraux (physiologie)</term><term>Réplication virale</term><term>Sites de fixation</term><term>Souris</term><term>Séquence nucléotidique</term><term>Virus de l'hépatite murine (génétique)</term><term>Virus de l'hépatite murine (pathogénicité)</term><term>Virus de l'hépatite murine (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Carcinoembryonic Antigen</term><term>DNA, Recombinant</term><term>Gene Products, vif</term><term>Membrane Glycoproteins</term><term>Receptors, Virus</term><term>Recombinant Proteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Recombinant Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Carcinoembryonic Antigen</term><term>Gene Products, vif</term><term>Membrane Glycoproteins</term><term>Receptors, Virus</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Murine hepatitis virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ADN recombiné</term><term>Antigène carcinoembryonnaire</term><term>Glycoprotéines membranaires</term><term>Produits du gène vif</term><term>Protéines de l'enveloppe virale</term><term>Protéines recombinantes</term><term>Récepteurs viraux</term><term>Virus de l'hépatite murine</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protéines recombinantes</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Murine hepatitis virus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus de l'hépatite murine</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Antigène carcinoembryonnaire</term><term>Glycoprotéines membranaires</term><term>Produits du gène vif</term><term>Protéines de l'enveloppe virale</term><term>Récepteurs viraux</term><term>Virus de l'hépatite murine</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Murine hepatitis virus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Base Sequence</term><term>Binding Sites</term><term>Cats</term><term>Cell Line</term><term>Humans</term><term>Membrane Fusion</term><term>Mice</term><term>Spike Glycoprotein, Coronavirus</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Chats</term><term>Fusion membranaire</term><term>Glycoprotéine de spicule des coronavirus</term><term>Humains</term><term>Lignée cellulaire</term><term>Réplication virale</term><term>Sites de fixation</term><term>Souris</term><term>Séquence nucléotidique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Murine hepatitis coronavirus (MHV)-A59 infection depends on the interaction of its spike (S) protein with the cellular receptor mCEACAM1a present on murine cells. Human cells lack this receptor and are therefore not susceptible to MHV. Specific alleviation of the tropism barrier by redirecting MHV to a tumor-specific receptor could lead to a virus with appealing properties for tumor therapy. To demonstrate that MHV can be retargeted to a nonnative receptor on human cells, we produced bispecific adapter proteins composed of the N-terminal D1 domain of mCEACAM1a linked to a short targeting peptide, the six-amino-acid His tag. Preincubation of MHV with the adapter proteins and subsequent inoculation of human cells expressing an artificial His receptor resulted in infection of these otherwise nonsusceptible cells and led to subsequent production of progeny virus. To generate a self-targeted virus able to establish multiround infection of the target cells, we subsequently incorporated the gene encoding the bispecific adapter protein as an additional expression cassette into the MHV genome through targeted RNA recombination. When inoculated onto murine LR7 cells, the resulting recombinant virus indeed expressed the adapter protein. Furthermore, inoculation of human target cells with the virus resulted in a His receptor-specific infection that was multiround. Extensive cell-cell fusion and rapid cell killing of infected target cells was observed. Our results show that MHV can be genetically redirected via adapters composed of the S protein binding part of mCEACAM1a and a targeting peptide recognizing a nonnative receptor expressed on human cells, consequently leading to rapid cell death. The results provide interesting leads for further investigations of the use of coronaviruses as antitumor agents.</div></front></TEI><affiliations><list><country><li>Pays-Bas</li></country><region><li>Utrecht (province)</li></region><settlement><li>Utrecht</li></settlement><orgName><li>Université d'Utrecht</li></orgName></list><tree><noCountry><name sortKey="De Haan, C A M" sort="De Haan, C A M" uniqKey="De Haan C" first="C A M" last="De Haan">C A M. De Haan</name><name sortKey="Gerritsen, W R" sort="Gerritsen, W R" uniqKey="Gerritsen W" first="W R" last="Gerritsen">W R Gerritsen</name><name sortKey="Rottier, P J M" sort="Rottier, P J M" uniqKey="Rottier P" first="P J M" last="Rottier">P J M. Rottier</name><name sortKey="Van Beusechem, V W" sort="Van Beusechem, V W" uniqKey="Van Beusechem V" first="V W" last="Van Beusechem">V W Van Beusechem</name><name sortKey="Wurdinger, T" sort="Wurdinger, T" uniqKey="Wurdinger T" first="T" last="Würdinger">T. Würdinger</name></noCountry><country name="Pays-Bas"><region name="Utrecht (province)"><name sortKey="Verheije, M H" sort="Verheije, M H" uniqKey="Verheije M" first="M H" last="Verheije">M H Verheije</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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