Exploitation of the Herpes simplex virus translocating protein VP22 to carry influenza virus proteins into cells for studies of apoptosis: direct confirmation that neuraminidase induces apoptosis and indications that other proteins may have a role
Identifieur interne : 001776 ( Main/Exploration ); précédent : 001775; suivant : 001777Exploitation of the Herpes simplex virus translocating protein VP22 to carry influenza virus proteins into cells for studies of apoptosis: direct confirmation that neuraminidase induces apoptosis and indications that other proteins may have a role
Auteurs : S. J. Morris [Royaume-Uni] ; H. Smith [Royaume-Uni] ; C. Sweet [Royaume-Uni]Source :
- Archives of Virology [ 0304-8608 ] ; 2002-05-01.
Abstract
Summary: Previously, we have shown that apoptosis induced by influenza virus was inhibited by an anti-neuraminidase compound [4-guanidino-2, 3-dehydro-N-acetylneuraminic acid (GG167; Relenza; Zanamivir)], which does not enter cells, and acts at the attachment/entry phase of virus replication. Furthermore, a virulent virus, clone 7a, induced greater levels of apoptosis than the attenuated A/Fiji and had greater neuraminidase (NA) activity. To confirm more directly that NA induces apoptosis, the NA of clone 7a and A/Fiji was expressed fused to the Herpes simplex virus tegument coat protein VP22, transfected into HeLa cells and the level of apoptosis determined. VP22 translocates between cells via the medium thus allowing expressed proteins to transfer to a larger number of cells than those originally transfected. Clone 7a NA fused to VP22 induced a significant level of apoptosis whereas A/Fiji NA/VP22 did not, confirming that NA activity is an important determinant of apoptosis acting during fusion protein translocation between cells. Furthermore, the induction of apoptosis was abrogated by antibody to transforming growth factor-β, which is activated by NA. This approach also showed that VP22/NS1 proteins of both clone 7a and A/Fiji induced apoptosis when expressed alone but inhibited double stranded RNA-induced apoptosis suggesting that this protein may have a dual mode of action. Also, the M1 and M2 proteins of both viruses induced apoptosis but their NP proteins did not.
Url:
DOI: 10.1007/s00705-001-0779-x
Affiliations:
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Exploitation of the Herpes simplex virus translocating protein VP22 to carry influenza virus proteins into cells for studies of apoptosis: direct confirmation that neuraminidase induces apoptosis and indications that other proteins may have a role</title><author><name sortKey="Morris, S J" sort="Morris, S J" uniqKey="Morris S" first="S. J." last="Morris">S. J. Morris</name></author><author><name sortKey="Smith, H" sort="Smith, H" uniqKey="Smith H" first="H." last="Smith">H. Smith</name></author><author><name sortKey="Sweet, C" sort="Sweet, C" uniqKey="Sweet C" first="C." last="Sweet">C. 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J." last="Morris">S. J. Morris</name><affiliation wicri:level="4"><orgName type="university">Université de Birmingham</orgName><country>Royaume-Uni</country><placeName><settlement type="city">Birmingham</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Midlands de l'Ouest</region></placeName></affiliation></author><author><name sortKey="Smith, H" sort="Smith, H" uniqKey="Smith H" first="H." last="Smith">H. Smith</name><affiliation wicri:level="4"><orgName type="university">Université de Birmingham</orgName><country>Royaume-Uni</country><placeName><settlement type="city">Birmingham</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Midlands de l'Ouest</region></placeName></affiliation></author><author><name sortKey="Sweet, C" sort="Sweet, C" uniqKey="Sweet C" first="C." last="Sweet">C. Sweet</name><affiliation wicri:level="4"><orgName type="university">Université de Birmingham</orgName><country>Royaume-Uni</country><placeName><settlement type="city">Birmingham</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Midlands de l'Ouest</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Archives of Virology</title><title level="j" type="abbrev">Arch. Virol.</title><idno type="ISSN">0304-8608</idno><idno type="eISSN">1432-8798</idno><imprint><publisher>Springer-Verlag</publisher><pubPlace>Vienna</pubPlace><date type="published" when="2002-05-01">2002-05-01</date><biblScope unit="volume">147</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="961">961</biblScope><biblScope unit="page" to="979">979</biblScope></imprint><idno type="ISSN">0304-8608</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0304-8608</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Summary: Previously, we have shown that apoptosis induced by influenza virus was inhibited by an anti-neuraminidase compound [4-guanidino-2, 3-dehydro-N-acetylneuraminic acid (GG167; Relenza; Zanamivir)], which does not enter cells, and acts at the attachment/entry phase of virus replication. Furthermore, a virulent virus, clone 7a, induced greater levels of apoptosis than the attenuated A/Fiji and had greater neuraminidase (NA) activity. To confirm more directly that NA induces apoptosis, the NA of clone 7a and A/Fiji was expressed fused to the Herpes simplex virus tegument coat protein VP22, transfected into HeLa cells and the level of apoptosis determined. VP22 translocates between cells via the medium thus allowing expressed proteins to transfer to a larger number of cells than those originally transfected. Clone 7a NA fused to VP22 induced a significant level of apoptosis whereas A/Fiji NA/VP22 did not, confirming that NA activity is an important determinant of apoptosis acting during fusion protein translocation between cells. Furthermore, the induction of apoptosis was abrogated by antibody to transforming growth factor-β, which is activated by NA. This approach also showed that VP22/NS1 proteins of both clone 7a and A/Fiji induced apoptosis when expressed alone but inhibited double stranded RNA-induced apoptosis suggesting that this protein may have a dual mode of action. Also, the M1 and M2 proteins of both viruses induced apoptosis but their NP proteins did not.</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Midlands de l'Ouest</li></region><settlement><li>Birmingham</li></settlement><orgName><li>Université de Birmingham</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Morris, S J" sort="Morris, S J" uniqKey="Morris S" first="S. J." last="Morris">S. J. Morris</name></region><name sortKey="Smith, H" sort="Smith, H" uniqKey="Smith H" first="H." last="Smith">H. Smith</name><name sortKey="Sweet, C" sort="Sweet, C" uniqKey="Sweet C" first="C." last="Sweet">C. 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