Sequence analysis of the spike protein gene of murine coronavirus variants: study of genetic sites affecting neuropathogenicity.
Identifieur interne : 000340 ( Ncbi/Curation ); précédent : 000339; suivant : 000341Sequence analysis of the spike protein gene of murine coronavirus variants: study of genetic sites affecting neuropathogenicity.
Auteurs : F I Wang [États-Unis] ; J O Fleming ; M M LaiSource :
- Virology [ 0042-6822 ] ; 1992.
Descripteurs français
- KwdFr :
- Animaux, Anticorps monoclonaux (immunologie), Cellules cancéreuses en culture, Clonage moléculaire, Coronaviridae (génétique), Coronaviridae (pathogénicité), Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Infections à Coronaviridae (microbiologie), Maladie du système nerveux central (microbiologie), Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (immunologie), Souris, Séquence nucléotidique, Tests de neutralisation, Variation génétique.
- MESH :
- génétique : Coronaviridae, Protéines de l'enveloppe virale.
- immunologie : Anticorps monoclonaux, Protéines de l'enveloppe virale.
- microbiologie : Infections à Coronaviridae, Maladie du système nerveux central.
- pathogénicité : Coronaviridae.
- Animaux, Cellules cancéreuses en culture, Clonage moléculaire, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Souris, Séquence nucléotidique, Tests de neutralisation, Variation génétique.
English descriptors
- KwdEn :
- Animals, Antibodies, Monoclonal (immunology), Base Sequence, Central Nervous System Diseases (microbiology), Cloning, Molecular, Coronaviridae (genetics), Coronaviridae (pathogenicity), Coronaviridae Infections (microbiology), Genetic Variation, Membrane Glycoproteins, Mice, Neutralization Tests, Spike Glycoprotein, Coronavirus, Tumor Cells, Cultured, Viral Envelope Proteins (genetics), Viral Envelope Proteins (immunology).
- MESH :
- chemical , genetics : Viral Envelope Proteins.
- chemical , immunology : Antibodies, Monoclonal, Viral Envelope Proteins.
- genetics : Coronaviridae.
- microbiology : Central Nervous System Diseases, Coronaviridae Infections.
- pathogenicity : Coronaviridae.
- Animals, Base Sequence, Cloning, Molecular, Genetic Variation, Membrane Glycoproteins, Mice, Neutralization Tests, Spike Glycoprotein, Coronavirus, Tumor Cells, Cultured.
Abstract
Mouse hepatitis virus (MHV), a coronavirus, causes encephalitis and demyelination in susceptible rodents. Previous investigations have shown that the MHV spike (S) protein is a critical determinant of viral tropism and pathogenicity in mice and rats. To understand the molecular basis of MHV neuropathogenesis, we studied the spike protein gene sequences of several neutralization-resistant variants of the JHM strain of MHV, which were selected with monoclonal antibodies (MAbs) specific for the S protein. We found that variant 2.2-V-1, which was selected with MAb J.2.2 and primarily caused demyelination, had a single point mutation at nucleotide (NT) 3340, as compared to the parental JHM virus, which predominantly caused encephalitis. This site was in the S2 subunit of the S protein. In contrast, variant 7.2-V-1, which was selected with MAb J.7.2 and primarily caused encephalitis, had two point mutations at NT 1766 and 1950, which were in the S1 subunit. Finally, the double mutant 2.2/7.2-V-2, which was selected with both MAbs J.2.2 and J.7.2, and was attenuated with respect to both virulence and the ability to cause demyelination, had a deletion spanning from NT 1523 to 1624 in the S1 and a point mutation at NT 3340 in the S2. We conclude that at least two regions of the S protein contribute to neuropathogenicity of MHV. We have also isolated a partial revertant of 2.2-V-1, which was partially resistant to MAb J.2.2 but retained the same neuropathogenicity as the variant 2.2-V-1. This revertant retained the mutation at NT 3340, but had a second-site mutation at NT 1994, further confirming that NT 3340 contributed to the pathogenic phenotype of MHV. By comparing these results with MHV variants isolated in other laboratories, which had mutations in other sites on the S gene and yet retained the demyelinating ability, we suggest that the ability of JHM viruses to induce demyelination is determined by the interaction of multiple sites on the S gene, rather than the characteristics of a single, unique site. Our study also revealed the possible presence of microheterogeneity of S gene sequence, particularly in the S1 region, in these viruses. The sequence microheterogeneity may also contribute to the differences in their biological properties.
DOI: 10.1016/0042-6822(92)90041-m
PubMed: 1310195
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: Pour aller vers cette notice dans l'étape Curation :003554
- to stream PubMed, to step Curation: Pour aller vers cette notice dans l'étape Curation :003554
- to stream PubMed, to step Checkpoint: Pour aller vers cette notice dans l'étape Curation :003440
- to stream Ncbi, to step Merge: Pour aller vers cette notice dans l'étape Curation :000340
Links to Exploration step
pubmed:1310195Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Sequence analysis of the spike protein gene of murine coronavirus variants: study of genetic sites affecting neuropathogenicity.</title>
<author><name sortKey="Wang, F I" sort="Wang, F I" uniqKey="Wang F" first="F I" last="Wang">F I Wang</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Neurology, School of Medicine, University of Southern California, Los Angeles 90033.</nlm:affiliation>
<orgName type="university">Université de Californie du Sud</orgName>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Fleming, J O" sort="Fleming, J O" uniqKey="Fleming J" first="J O" last="Fleming">J O Fleming</name>
</author>
<author><name sortKey="Lai, M M" sort="Lai, M M" uniqKey="Lai M" first="M M" last="Lai">M M Lai</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="1992">1992</date>
<idno type="RBID">pubmed:1310195</idno>
<idno type="pmid">1310195</idno>
<idno type="doi">10.1016/0042-6822(92)90041-m</idno>
<idno type="wicri:Area/PubMed/Corpus">003554</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">003554</idno>
<idno type="wicri:Area/PubMed/Curation">003554</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">003554</idno>
<idno type="wicri:Area/PubMed/Checkpoint">003440</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">003440</idno>
<idno type="wicri:Area/Ncbi/Merge">000340</idno>
<idno type="wicri:Area/Ncbi/Curation">000340</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Sequence analysis of the spike protein gene of murine coronavirus variants: study of genetic sites affecting neuropathogenicity.</title>
<author><name sortKey="Wang, F I" sort="Wang, F I" uniqKey="Wang F" first="F I" last="Wang">F I Wang</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Neurology, School of Medicine, University of Southern California, Los Angeles 90033.</nlm:affiliation>
<orgName type="university">Université de Californie du Sud</orgName>
<country>États-Unis</country>
<placeName><settlement type="city">Los Angeles</settlement>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Fleming, J O" sort="Fleming, J O" uniqKey="Fleming J" first="J O" last="Fleming">J O Fleming</name>
</author>
<author><name sortKey="Lai, M M" sort="Lai, M M" uniqKey="Lai M" first="M M" last="Lai">M M Lai</name>
</author>
</analytic>
<series><title level="j">Virology</title>
<idno type="ISSN">0042-6822</idno>
<imprint><date when="1992" type="published">1992</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Antibodies, Monoclonal (immunology)</term>
<term>Base Sequence</term>
<term>Central Nervous System Diseases (microbiology)</term>
<term>Cloning, Molecular</term>
<term>Coronaviridae (genetics)</term>
<term>Coronaviridae (pathogenicity)</term>
<term>Coronaviridae Infections (microbiology)</term>
<term>Genetic Variation</term>
<term>Membrane Glycoproteins</term>
<term>Mice</term>
<term>Neutralization Tests</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Tumor Cells, Cultured</term>
<term>Viral Envelope Proteins (genetics)</term>
<term>Viral Envelope Proteins (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Anticorps monoclonaux (immunologie)</term>
<term>Cellules cancéreuses en culture</term>
<term>Clonage moléculaire</term>
<term>Coronaviridae (génétique)</term>
<term>Coronaviridae (pathogénicité)</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires</term>
<term>Infections à Coronaviridae (microbiologie)</term>
<term>Maladie du système nerveux central (microbiologie)</term>
<term>Protéines de l'enveloppe virale (génétique)</term>
<term>Protéines de l'enveloppe virale (immunologie)</term>
<term>Souris</term>
<term>Séquence nucléotidique</term>
<term>Tests de neutralisation</term>
<term>Variation génétique</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Monoclonal</term>
<term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Coronaviridae</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Coronaviridae</term>
<term>Protéines de l'enveloppe virale</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps monoclonaux</term>
<term>Protéines de l'enveloppe virale</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr"><term>Infections à Coronaviridae</term>
<term>Maladie du système nerveux central</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Central Nervous System Diseases</term>
<term>Coronaviridae Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Coronaviridae</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Coronaviridae</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Base Sequence</term>
<term>Cloning, Molecular</term>
<term>Genetic Variation</term>
<term>Membrane Glycoproteins</term>
<term>Mice</term>
<term>Neutralization Tests</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Tumor Cells, Cultured</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cellules cancéreuses en culture</term>
<term>Clonage moléculaire</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires</term>
<term>Souris</term>
<term>Séquence nucléotidique</term>
<term>Tests de neutralisation</term>
<term>Variation génétique</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Mouse hepatitis virus (MHV), a coronavirus, causes encephalitis and demyelination in susceptible rodents. Previous investigations have shown that the MHV spike (S) protein is a critical determinant of viral tropism and pathogenicity in mice and rats. To understand the molecular basis of MHV neuropathogenesis, we studied the spike protein gene sequences of several neutralization-resistant variants of the JHM strain of MHV, which were selected with monoclonal antibodies (MAbs) specific for the S protein. We found that variant 2.2-V-1, which was selected with MAb J.2.2 and primarily caused demyelination, had a single point mutation at nucleotide (NT) 3340, as compared to the parental JHM virus, which predominantly caused encephalitis. This site was in the S2 subunit of the S protein. In contrast, variant 7.2-V-1, which was selected with MAb J.7.2 and primarily caused encephalitis, had two point mutations at NT 1766 and 1950, which were in the S1 subunit. Finally, the double mutant 2.2/7.2-V-2, which was selected with both MAbs J.2.2 and J.7.2, and was attenuated with respect to both virulence and the ability to cause demyelination, had a deletion spanning from NT 1523 to 1624 in the S1 and a point mutation at NT 3340 in the S2. We conclude that at least two regions of the S protein contribute to neuropathogenicity of MHV. We have also isolated a partial revertant of 2.2-V-1, which was partially resistant to MAb J.2.2 but retained the same neuropathogenicity as the variant 2.2-V-1. This revertant retained the mutation at NT 3340, but had a second-site mutation at NT 1994, further confirming that NT 3340 contributed to the pathogenic phenotype of MHV. By comparing these results with MHV variants isolated in other laboratories, which had mutations in other sites on the S gene and yet retained the demyelinating ability, we suggest that the ability of JHM viruses to induce demyelination is determined by the interaction of multiple sites on the S gene, rather than the characteristics of a single, unique site. Our study also revealed the possible presence of microheterogeneity of S gene sequence, particularly in the S1 region, in these viruses. The sequence microheterogeneity may also contribute to the differences in their biological properties.</div>
</front>
</TEI>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Ncbi/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000340 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Curation/biblio.hfd -nk 000340 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= SrasV1 |flux= Ncbi |étape= Curation |type= RBID |clé= pubmed:1310195 |texte= Sequence analysis of the spike protein gene of murine coronavirus variants: study of genetic sites affecting neuropathogenicity. }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Curation/RBID.i -Sk "pubmed:1310195" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Curation/biblio.hfd \ | NlmPubMed2Wicri -a SrasV1
![]() | This area was generated with Dilib version V0.6.33. | ![]() |