Mouse hepatitis virus spike and nucleocapsid proteins expressed by adenovirus vectors protect mice against a lethal infection.
Identifieur interne : 006B02 ( Main/Merge ); précédent : 006B01; suivant : 006B03Mouse hepatitis virus spike and nucleocapsid proteins expressed by adenovirus vectors protect mice against a lethal infection.
Auteurs : J G Wesseling [Pays-Bas] ; G J Godeke ; V E Schijns ; L. Prevec ; F L Graham ; M C Horzinek ; P J RottierSource :
- The Journal of general virology [ 0022-1317 ] ; 1993.
Descripteurs français
- KwdFr :
- Adénovirus humains, Animaux, Anticorps antiviraux (sang), Capside (génétique), Capside (immunologie), Cellules HeLa, Clonage moléculaire, Femelle, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Gènes viraux (génétique), Humains, Hépatite virale animale (immunologie), Infections à coronavirus (immunologie), Infections à coronavirus (médecine vétérinaire), Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (immunologie), Protéines du core viral (génétique), Protéines du core viral (immunologie), Recombinaison génétique, Souris, Souris de lignée BALB C, Vecteurs génétiques, Virus de l'hépatite murine (génétique), Virus de l'hépatite murine (immunologie).
- MESH :
- génétique : Capside, Gènes viraux, Protéines de l'enveloppe virale, Protéines du core viral, Virus de l'hépatite murine.
- immunologie : Capside, Hépatite virale animale, Infections à coronavirus, Protéines de l'enveloppe virale, Protéines du core viral, Virus de l'hépatite murine.
- médecine vétérinaire : Infections à coronavirus.
- sang : Anticorps antiviraux.
- Adénovirus humains, Animaux, Cellules HeLa, Clonage moléculaire, Femelle, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Humains, Recombinaison génétique, Souris, Souris de lignée BALB C, Vecteurs génétiques.
English descriptors
- KwdEn :
- Adenoviruses, Human, Animals, Antibodies, Viral (blood), Capsid (genetics), Capsid (immunology), Cloning, Molecular, Coronavirus Infections (immunology), Coronavirus Infections (veterinary), Female, Genes, Viral (genetics), Genetic Vectors, HeLa Cells, Hepatitis, Viral, Animal (immunology), Humans, Membrane Glycoproteins, Mice, Mice, Inbred BALB C, Murine hepatitis virus (genetics), Murine hepatitis virus (immunology), Recombination, Genetic, Spike Glycoprotein, Coronavirus, Viral Core Proteins (genetics), Viral Core Proteins (immunology), Viral Envelope Proteins (genetics), Viral Envelope Proteins (immunology).
- MESH :
- chemical , blood : Antibodies, Viral.
- genetics : Capsid, Genes, Viral, Murine hepatitis virus, Viral Core Proteins, Viral Envelope Proteins.
- immunology : Capsid, Coronavirus Infections, Hepatitis, Viral, Animal, Murine hepatitis virus, Viral Core Proteins, Viral Envelope Proteins.
- veterinary : Coronavirus Infections.
- Adenoviruses, Human, Animals, Cloning, Molecular, Female, Genetic Vectors, HeLa Cells, Humans, Membrane Glycoproteins, Mice, Mice, Inbred BALB C, Recombination, Genetic, Spike Glycoprotein, Coronavirus.
Abstract
Infection with the mouse hepatitis coronavirus (MHV) provides an excellent model for the study of viral diseases of the central nervous system and the gastrointestinal tract. With the ultimate aim of studying mucosal immunity to MHV we have cloned the genes encoding the structural proteins of MHV strain A59 (MHV-A59) into the E3 region of a human adenovirus type 5 vector. Infection of HeLa cells with the resulting recombinant adenoviruses AdMHVS, AdMHVN and AdMHVM revealed the correct expression of the spike (S), nucleocapsid (N) and membrane (M) proteins, respectively. Intraperitoneal inoculation of BALB/c mice with the recombinant viruses elicited serum antibodies which specifically recognized the respective MHV proteins in an immunoprecipitation assay. Only antibodies to the S protein neutralized MHV-A59 in vitro but titres were low. When analysed by ELISA or by immunofluorescence only the antibody response to the N protein was significant; weak responses or no detectable response at all were found for S and M, respectively. Upon intracerebral challenge with a lethal dose of MHV-A59 we found that a significant fraction of animals vaccinated with adenovirus vectors expressing either the S protein or N protein were protected. This protective effect was significantly stronger when the animals were given a booster immunization with the same vector prior to challenge. No protection was induced by AdMHVM. Interestingly, enhanced protection resulted when AdMHVS and AdMHVN were applied in combination as compared to survival after single immunizations. The results indicate that both the N and S proteins generate a protective immune response and suggest that this response is enhanced by combined expression of the two proteins.
DOI: 10.1099/0022-1317-74-10-2061
PubMed: 8409930
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pubmed:8409930Le document en format XML
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<term>Animals</term>
<term>Antibodies, Viral (blood)</term>
<term>Capsid (genetics)</term>
<term>Capsid (immunology)</term>
<term>Cloning, Molecular</term>
<term>Coronavirus Infections (immunology)</term>
<term>Coronavirus Infections (veterinary)</term>
<term>Female</term>
<term>Genes, Viral (genetics)</term>
<term>Genetic Vectors</term>
<term>HeLa Cells</term>
<term>Hepatitis, Viral, Animal (immunology)</term>
<term>Humans</term>
<term>Membrane Glycoproteins</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Murine hepatitis virus (genetics)</term>
<term>Murine hepatitis virus (immunology)</term>
<term>Recombination, Genetic</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Viral Core Proteins (genetics)</term>
<term>Viral Core Proteins (immunology)</term>
<term>Viral Envelope Proteins (genetics)</term>
<term>Viral Envelope Proteins (immunology)</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>Adénovirus humains</term>
<term>Animaux</term>
<term>Anticorps antiviraux (sang)</term>
<term>Capside (génétique)</term>
<term>Capside (immunologie)</term>
<term>Cellules HeLa</term>
<term>Clonage moléculaire</term>
<term>Femelle</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires</term>
<term>Gènes viraux (génétique)</term>
<term>Humains</term>
<term>Hépatite virale animale (immunologie)</term>
<term>Infections à coronavirus (immunologie)</term>
<term>Infections à coronavirus (médecine vétérinaire)</term>
<term>Protéines de l'enveloppe virale (génétique)</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Protéines du core viral (génétique)</term>
<term>Protéines du core viral (immunologie)</term>
<term>Recombinaison génétique</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Vecteurs génétiques</term>
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<term>Virus de l'hépatite murine (immunologie)</term>
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<term>Viral Core Proteins</term>
<term>Viral Envelope Proteins</term>
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<term>Gènes viraux</term>
<term>Protéines de l'enveloppe virale</term>
<term>Protéines du core viral</term>
<term>Virus de l'hépatite murine</term>
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<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Capside</term>
<term>Hépatite virale animale</term>
<term>Infections à coronavirus</term>
<term>Protéines de l'enveloppe virale</term>
<term>Protéines du core viral</term>
<term>Virus de l'hépatite murine</term>
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<term>Coronavirus Infections</term>
<term>Hepatitis, Viral, Animal</term>
<term>Murine hepatitis virus</term>
<term>Viral Core Proteins</term>
<term>Viral Envelope Proteins</term>
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<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Anticorps antiviraux</term>
</keywords>
<keywords scheme="MESH" qualifier="veterinary" xml:lang="en"><term>Coronavirus Infections</term>
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<term>Animals</term>
<term>Cloning, Molecular</term>
<term>Female</term>
<term>Genetic Vectors</term>
<term>HeLa Cells</term>
<term>Humans</term>
<term>Membrane Glycoproteins</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Recombination, Genetic</term>
<term>Spike Glycoprotein, Coronavirus</term>
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<term>Animaux</term>
<term>Cellules HeLa</term>
<term>Clonage moléculaire</term>
<term>Femelle</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires</term>
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<front><div type="abstract" xml:lang="en">Infection with the mouse hepatitis coronavirus (MHV) provides an excellent model for the study of viral diseases of the central nervous system and the gastrointestinal tract. With the ultimate aim of studying mucosal immunity to MHV we have cloned the genes encoding the structural proteins of MHV strain A59 (MHV-A59) into the E3 region of a human adenovirus type 5 vector. Infection of HeLa cells with the resulting recombinant adenoviruses AdMHVS, AdMHVN and AdMHVM revealed the correct expression of the spike (S), nucleocapsid (N) and membrane (M) proteins, respectively. Intraperitoneal inoculation of BALB/c mice with the recombinant viruses elicited serum antibodies which specifically recognized the respective MHV proteins in an immunoprecipitation assay. Only antibodies to the S protein neutralized MHV-A59 in vitro but titres were low. When analysed by ELISA or by immunofluorescence only the antibody response to the N protein was significant; weak responses or no detectable response at all were found for S and M, respectively. Upon intracerebral challenge with a lethal dose of MHV-A59 we found that a significant fraction of animals vaccinated with adenovirus vectors expressing either the S protein or N protein were protected. This protective effect was significantly stronger when the animals were given a booster immunization with the same vector prior to challenge. No protection was induced by AdMHVM. Interestingly, enhanced protection resulted when AdMHVS and AdMHVN were applied in combination as compared to survival after single immunizations. The results indicate that both the N and S proteins generate a protective immune response and suggest that this response is enhanced by combined expression of the two proteins.</div>
</front>
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