Redirecting coronavirus to a nonnative receptor through a virus-encoded targeting adapter.
Identifieur interne : 002381 ( PubMed/Corpus ); précédent : 002380; suivant : 002382Redirecting coronavirus to a nonnative receptor through a virus-encoded targeting adapter.
Auteurs : M H Verheije ; T. Würdinger ; V W Van Beusechem ; C A M. De Haan ; W R Gerritsen ; P J M. RottierSource :
- Journal of virology [ 0022-538X ] ; 2006.
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
Links to Exploration step
pubmed:16415002Le document en format XML
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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></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2006">2006</date><idno type="RBID">pubmed:16415002</idno><idno type="pmid">16415002</idno><idno type="doi">10.1128/JVI.80.3.1250-1260.2006</idno><idno type="wicri:Area/PubMed/Corpus">002381</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002381</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Redirecting coronavirus to a nonnative receptor through a virus-encoded targeting adapter.</title><author><name sortKey="Verheije, M H" sort="Verheije, M H" uniqKey="Verheije M" first="M H" last="Verheije">M H Verheije</name><affiliation><nlm:affiliation>Virology Division, Department of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Wurdinger, T" sort="Wurdinger, T" uniqKey="Wurdinger T" first="T" last="Würdinger">T. 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="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="pathogenicity" xml:lang="en"><term>Murine hepatitis virus</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></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><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">16415002</PMID><DateCompleted><Year>2006</Year><Month>02</Month><Day>27</Day></DateCompleted><DateRevised><Year>2020</Year><Month>04</Month><Day>15</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0022-538X</ISSN><JournalIssue CitedMedium="Print"><Volume>80</Volume><Issue>3</Issue><PubDate><Year>2006</Year><Month>Feb</Month></PubDate></JournalIssue><Title>Journal of virology</Title><ISOAbbreviation>J. Virol.</ISOAbbreviation></Journal><ArticleTitle>Redirecting coronavirus to a nonnative receptor through a virus-encoded targeting adapter.</ArticleTitle><Pagination><MedlinePgn>1250-60</MedlinePgn></Pagination><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Verheije</LastName><ForeName>M H</ForeName><Initials>MH</Initials><AffiliationInfo><Affiliation>Virology Division, Department of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Würdinger</LastName><ForeName>T</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>van Beusechem</LastName><ForeName>V W</ForeName><Initials>VW</Initials></Author><Author ValidYN="Y"><LastName>de Haan</LastName><ForeName>C A M</ForeName><Initials>CA</Initials></Author><Author ValidYN="Y"><LastName>Gerritsen</LastName><ForeName>W R</ForeName><Initials>WR</Initials></Author><Author ValidYN="Y"><LastName>Rottier</LastName><ForeName>P J M</ForeName><Initials>PJ</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Virol</MedlineTA><NlmUniqueID>0113724</NlmUniqueID><ISSNLinking>0022-538X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002272">Carcinoembryonic Antigen</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C486183">Ceacam1 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004274">DNA, Recombinant</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016346">Gene Products, vif</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C578553">MHV surface projection glycoprotein</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D008562">Membrane Glycoproteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011991">Receptors, Virus</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011994">Recombinant Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D064370">Spike Glycoprotein, Coronavirus</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014759">Viral Envelope Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C578557">spike glycoprotein, 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MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016346" MajorTopicYN="N">Gene Products, vif</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008561" MajorTopicYN="N">Membrane Fusion</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008562" MajorTopicYN="N">Membrane Glycoproteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006517" MajorTopicYN="N">Murine hepatitis virus</DescriptorName><QualifierName UI="Q000235" 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