Soluble receptor-mediated targeting of mouse hepatitis coronavirus to the human epidermal growth factor receptor.
Identifieur interne : 004621 ( Main/Exploration ); précédent : 004620; suivant : 004622Soluble receptor-mediated targeting of mouse hepatitis coronavirus to the human epidermal growth factor receptor.
Auteurs : T. Würdinger [Pays-Bas] ; M H Verheije ; K. Broen ; B J Bosch ; B J Haijema ; C A M. De Haan ; V W Van Beusechem ; W R Gerritsen ; P J M. RottierSource :
- Journal of virology [ 0022-538X ] ; 2005.
Descripteurs français
- KwdFr :
- Animaux, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (), Glycoprotéines membranaires (physiologie), Humains, Infections à coronavirus (immunologie), Infections à coronavirus (métabolisme), Protéines de l'enveloppe virale (), Protéines de l'enveloppe virale (physiologie), Récepteurs ErbB (métabolisme), Souris, Virus de l'hépatite murine (physiologie).
- MESH :
- immunologie : Infections à coronavirus.
- métabolisme : Infections à coronavirus, Récepteurs ErbB.
- physiologie : Glycoprotéines membranaires, Protéines de l'enveloppe virale, Virus de l'hépatite murine.
- Animaux, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Humains, Protéines de l'enveloppe virale, Souris.
English descriptors
- KwdEn :
- Animals, Coronavirus Infections (immunology), Coronavirus Infections (metabolism), ErbB Receptors (metabolism), Humans, Membrane Glycoproteins (chemistry), Membrane Glycoproteins (physiology), Mice, Murine hepatitis virus (physiology), Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (chemistry), Viral Envelope Proteins (physiology).
- MESH :
- chemical , chemistry : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , metabolism : ErbB Receptors.
- immunology : Coronavirus Infections.
- metabolism : Coronavirus Infections.
- chemical , physiology : Membrane Glycoproteins, Murine hepatitis virus, Viral Envelope Proteins.
- Animals, Humans, Mice, Spike Glycoprotein, Coronavirus.
Abstract
The mouse hepatitis coronavirus (MHV) infects murine cells by binding of its spike (S) protein to murine CEACAM1a. The N-terminal part of this cellular receptor (soR) is sufficient for S binding and for subsequent induction of the conformational changes required for virus-cell membrane fusion. Here we analyzed whether these characteristics can be used to redirect MHV to human cancer cells. To this end, the soR domain was coupled to single-chain monoclonal antibody 425, which is directed against the human epidermal growth factor receptor (EGFR), resulting in a bispecific adapter protein (soR-425). The soR and soR-425 proteins, both produced with the vaccinia virus system, were able to neutralize MHV infection of murine LR7 cells. However, only soR-425 was able to target MHV to human EGFR-expressing cancer cells. Interestingly, the targeted infections induced syncytium formation. Furthermore, the soR-425-mediated infections were blocked by heptad repeat-mimicking peptides, indicating that virus entry requires the regular S protein fusion process. We conclude that the specific spike-binding property of the CEACAM1a N-terminal fragment can be exploited to direct the virus to selected cells by linking it to a moiety able to bind a receptor on those cells. This approach might be useful in the development of tumor-targeted coronaviruses.
DOI: 10.1128/JVI.79.24.15314-15322.2005
PubMed: 16306602
Affiliations:
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Le document en format XML
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Würdinger</name><affiliation wicri:level="4"><nlm:affiliation>Virology Division, Department of Infectious Diseases & Immunology, Utrecht University, 3584 CL Utrecht, The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Virology Division, Department of Infectious Diseases & Immunology, Utrecht University, 3584 CL Utrecht</wicri:regionArea><orgName type="university">Université d'Utrecht</orgName><placeName><settlement type="city">Utrecht</settlement><region nuts="2">Utrecht (province)</region></placeName></affiliation></author><author><name sortKey="Verheije, M H" sort="Verheije, M H" uniqKey="Verheije M" first="M H" last="Verheije">M H Verheije</name></author><author><name sortKey="Broen, K" sort="Broen, K" uniqKey="Broen K" first="K" last="Broen">K. Broen</name></author><author><name sortKey="Bosch, B J" sort="Bosch, B J" uniqKey="Bosch B" first="B J" last="Bosch">B J Bosch</name></author><author><name sortKey="Haijema, B J" sort="Haijema, B J" uniqKey="Haijema B" first="B J" last="Haijema">B J Haijema</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="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="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="2005" type="published">2005</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Coronavirus Infections (immunology)</term><term>Coronavirus Infections (metabolism)</term><term>ErbB Receptors (metabolism)</term><term>Humans</term><term>Membrane Glycoproteins (chemistry)</term><term>Membrane Glycoproteins (physiology)</term><term>Mice</term><term>Murine hepatitis virus (physiology)</term><term>Spike Glycoprotein, Coronavirus</term><term>Viral Envelope Proteins (chemistry)</term><term>Viral Envelope Proteins (physiology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires ()</term><term>Glycoprotéines membranaires (physiologie)</term><term>Humains</term><term>Infections à coronavirus (immunologie)</term><term>Infections à coronavirus (métabolisme)</term><term>Protéines de l'enveloppe virale ()</term><term>Protéines de l'enveloppe virale (physiologie)</term><term>Récepteurs ErbB (métabolisme)</term><term>Souris</term><term>Virus de l'hépatite murine (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>ErbB Receptors</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Infections à coronavirus</term><term>Récepteurs ErbB</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term><term>Virus de l'hépatite murine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Membrane Glycoproteins</term><term>Murine hepatitis virus</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Humans</term><term>Mice</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires</term><term>Humains</term><term>Protéines de l'enveloppe virale</term><term>Souris</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The mouse hepatitis coronavirus (MHV) infects murine cells by binding of its spike (S) protein to murine CEACAM1a. The N-terminal part of this cellular receptor (soR) is sufficient for S binding and for subsequent induction of the conformational changes required for virus-cell membrane fusion. Here we analyzed whether these characteristics can be used to redirect MHV to human cancer cells. To this end, the soR domain was coupled to single-chain monoclonal antibody 425, which is directed against the human epidermal growth factor receptor (EGFR), resulting in a bispecific adapter protein (soR-425). The soR and soR-425 proteins, both produced with the vaccinia virus system, were able to neutralize MHV infection of murine LR7 cells. However, only soR-425 was able to target MHV to human EGFR-expressing cancer cells. Interestingly, the targeted infections induced syncytium formation. Furthermore, the soR-425-mediated infections were blocked by heptad repeat-mimicking peptides, indicating that virus entry requires the regular S protein fusion process. We conclude that the specific spike-binding property of the CEACAM1a N-terminal fragment can be exploited to direct the virus to selected cells by linking it to a moiety able to bind a receptor on those cells. This approach might be useful in the development of tumor-targeted coronaviruses.</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="Bosch, B J" sort="Bosch, B J" uniqKey="Bosch B" first="B J" last="Bosch">B J Bosch</name><name sortKey="Broen, K" sort="Broen, K" uniqKey="Broen K" first="K" last="Broen">K. Broen</name><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="Haijema, B J" sort="Haijema, B J" uniqKey="Haijema B" first="B J" last="Haijema">B J Haijema</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="Verheije, M H" sort="Verheije, M H" uniqKey="Verheije M" first="M H" last="Verheije">M H Verheije</name></noCountry><country name="Pays-Bas"><region name="Utrecht (province)"><name sortKey="Wurdinger, T" sort="Wurdinger, T" uniqKey="Wurdinger T" first="T" last="Würdinger">T. Würdinger</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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