Cells Expressing the RING Finger Z Protein Are Resistant to Arenavirus Infection
Identifieur interne : 000214 ( Pmc/Curation ); précédent : 000213; suivant : 000215Cells Expressing the RING Finger Z Protein Are Resistant to Arenavirus Infection
Auteurs : Tatjana I. Cornu ; Heinz Feldmann ; Juan Carlos De La TorreSource :
- Journal of Virology [ 0022-538X ] ; 2004.
Abstract
Arenaviruses include Lassa fever virus (LFV) and the South American hemorrhagic fever viruses. These viruses cause severe human disease, and they pose a threat as agents of bioterrorism. Arenaviruses are enveloped viruses with a bisegmented negative-strand RNA genome whose proteomic capability is limited to four polypeptides: nucleoprotein (NP); surface glycoprotein (GP), which is proteolytically processed into GP1 and GP2; polymerase (L); and a small (11-kDa) RING finger protein (Z). Our investigators have previously shown that Z has a strong inhibitory activity on RNA synthesis mediated by the polymerase of the prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV). In this report we show that cells transduced with a replication-deficient recombinant adenovirus expressing Z (rAd-Z) are resistant to LCMV and LFV infection. Virus cell entry mediated by LCMV or LFV GP was not affected in rAd-Z-transduced cells, but both virus transcription and replication were strongly and specifically inhibited, which resulted in a dramatic reduction in production of infectious virus. These findings open new avenues for developing antiviral strategies to combat the highly pathogenic human arenaviruses, including LFV.
Url:
DOI: 10.1128/JVI.78.6.2979-2983.2004
PubMed: 14990716
PubMed Central: 353761
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<series><title level="j">Journal of Virology</title>
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<front><div type="abstract" xml:lang="en"><p>Arenaviruses include Lassa fever virus (LFV) and the South American hemorrhagic fever viruses. These viruses cause severe human disease, and they pose a threat as agents of bioterrorism. Arenaviruses are enveloped viruses with a bisegmented negative-strand RNA genome whose proteomic capability is limited to four polypeptides: nucleoprotein (NP); surface glycoprotein (GP), which is proteolytically processed into GP1 and GP2; polymerase (L); and a small (11-kDa) RING finger protein (Z). Our investigators have previously shown that Z has a strong inhibitory activity on RNA synthesis mediated by the polymerase of the prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV). In this report we show that cells transduced with a replication-deficient recombinant adenovirus expressing Z (rAd-Z) are resistant to LCMV and LFV infection. Virus cell entry mediated by LCMV or LFV GP was not affected in rAd-Z-transduced cells, but both virus transcription and replication were strongly and specifically inhibited, which resulted in a dramatic reduction in production of infectious virus. These findings open new avenues for developing antiviral strategies to combat the highly pathogenic human arenaviruses, including LFV.</p>
</div>
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<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Virol</journal-id>
<journal-id journal-id-type="publisher-id">jvi</journal-id>
<journal-title>Journal of Virology</journal-title>
<issn pub-type="ppub">0022-538X</issn>
<issn pub-type="epub">1098-5514</issn>
<publisher><publisher-name>American Society for Microbiology</publisher-name>
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<article-id pub-id-type="publisher-id">1939</article-id>
<article-id pub-id-type="doi">10.1128/JVI.78.6.2979-2983.2004</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Virus-Cell Interactions</subject>
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<title-group><article-title>Cells Expressing the RING Finger Z Protein Are Resistant to Arenavirus Infection</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Cornu</surname>
<given-names>Tatjana I.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
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<contrib contrib-type="author"><name><surname>Feldmann</surname>
<given-names>Heinz</given-names>
</name>
<xref ref-type="aff" rid="aff1">2</xref>
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<contrib contrib-type="author"><name><surname>de la Torre</surname>
<given-names>Juan Carlos</given-names>
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<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
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<aff id="aff1">Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037,<label>1</label>
Special Pathogens Program, National Microbiology Laboratory, Health Canada, Winnipeg, Manitoba, Canada R3E 3R2<label>2</label>
</aff>
<author-notes><fn id="cor1"><label>*</label>
<p>Corresponding author. Mailing address: Dept. of Neuropharmacology, The Scripps Research Institute, IMM-6, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-9462. Fax: (858) 784-9981. E-mail: <email>juanct@scripps.edu</email>
.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>3</month>
<year>2004</year>
</pub-date>
<volume>78</volume>
<issue>6</issue>
<fpage>2979</fpage>
<lpage>2983</lpage>
<history><date date-type="received"><day>12</day>
<month>9</month>
<year>2003</year>
</date>
<date date-type="accepted"><day>18</day>
<month>11</month>
<year>2003</year>
</date>
</history>
<copyright-statement>Copyright © 2004, American Society for Microbiology</copyright-statement>
<copyright-year>2004</copyright-year>
<abstract><p>Arenaviruses include Lassa fever virus (LFV) and the South American hemorrhagic fever viruses. These viruses cause severe human disease, and they pose a threat as agents of bioterrorism. Arenaviruses are enveloped viruses with a bisegmented negative-strand RNA genome whose proteomic capability is limited to four polypeptides: nucleoprotein (NP); surface glycoprotein (GP), which is proteolytically processed into GP1 and GP2; polymerase (L); and a small (11-kDa) RING finger protein (Z). Our investigators have previously shown that Z has a strong inhibitory activity on RNA synthesis mediated by the polymerase of the prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV). In this report we show that cells transduced with a replication-deficient recombinant adenovirus expressing Z (rAd-Z) are resistant to LCMV and LFV infection. Virus cell entry mediated by LCMV or LFV GP was not affected in rAd-Z-transduced cells, but both virus transcription and replication were strongly and specifically inhibited, which resulted in a dramatic reduction in production of infectious virus. These findings open new avenues for developing antiviral strategies to combat the highly pathogenic human arenaviruses, including LFV.</p>
</abstract>
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