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Article: Structure of Crimean-Congo hemorrhagic fever virus nucleoprotein: superhelical homo-oligomers and the role of caspase-3 cleavage

TitleStructure of Crimean-Congo hemorrhagic fever virus nucleoprotein: superhelical homo-oligomers and the role of caspase-3 cleavage
Authors
Issue Date2012
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
Citation
Journal of Virology, 2012, v. 86 n. 22, p. 12294-12303 How to Cite?
AbstractCrimean-Congo hemorrhagic fever, a severe hemorrhagic disease found throughout Africa, Europe, and Asia, is caused by the tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV). CCHFV is a negative-sense single-stranded RNA (ssRNA) virus belonging to the Nairovirus genus of the Bunyaviridae family. Its genome of three single-stranded RNA segments is encapsidated by the nucleocapsid protein (CCHFV N) to form the ribonucleoprotein complex. This ribonucleoprotein complex is required during replication and transcription of the viral genomic RNA. Here, we present the crystal structures of the CCHFV N in two distinct forms, an oligomeric form comprised of double antiparallel superhelices and a monomeric form. The head-to-tail interaction of the stalk region of one CCHFV N subunit with the base of the globular body of the adjacent subunit stabilizes the helical organization of the oligomeric form of CCHFV N. It also masks the conserved caspase-3 cleavage site present at the tip of the stalk region from host cell caspase-3 interaction and cleavage. By incubation with primer-length ssRNAs, we also obtained the crystal structure of CCHFV N in its monomeric form, which is similar to a recently published structure. The conformational change of CCHFV N upon deoligomerization results in the exposure of the caspase-3 cleavage site and subjects CCHFV N to caspase-3 cleavage. Mutations of this cleavage site inhibit cleavage by caspase-3 and result in enhanced viral polymerase activity. Thus, cleavage of CCHFV N by host cell caspase-3 appears to be crucial for controlling viral RNA synthesis and represents an important host defense mechanism against CCHFV infection.
Persistent Identifierhttp://hdl.handle.net/10722/164529
ISSN
2015 Impact Factor: 4.606
2015 SCImago Journal Rankings: 3.347
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, Yen_US
dc.contributor.authorDutta, Sen_US
dc.contributor.authorKarlberg, Hen_US
dc.contributor.authorDevignot, Sen_US
dc.contributor.authorWeber, Fen_US
dc.contributor.authorHao, Qen_US
dc.contributor.authorTan, YJen_US
dc.contributor.authorMirazimi, Aen_US
dc.contributor.authorKotaka, Men_US
dc.date.accessioned2012-09-20T08:05:20Z-
dc.date.available2012-09-20T08:05:20Z-
dc.date.issued2012en_US
dc.identifier.citationJournal of Virology, 2012, v. 86 n. 22, p. 12294-12303en_US
dc.identifier.issn0022-538X-
dc.identifier.urihttp://hdl.handle.net/10722/164529-
dc.description.abstractCrimean-Congo hemorrhagic fever, a severe hemorrhagic disease found throughout Africa, Europe, and Asia, is caused by the tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV). CCHFV is a negative-sense single-stranded RNA (ssRNA) virus belonging to the Nairovirus genus of the Bunyaviridae family. Its genome of three single-stranded RNA segments is encapsidated by the nucleocapsid protein (CCHFV N) to form the ribonucleoprotein complex. This ribonucleoprotein complex is required during replication and transcription of the viral genomic RNA. Here, we present the crystal structures of the CCHFV N in two distinct forms, an oligomeric form comprised of double antiparallel superhelices and a monomeric form. The head-to-tail interaction of the stalk region of one CCHFV N subunit with the base of the globular body of the adjacent subunit stabilizes the helical organization of the oligomeric form of CCHFV N. It also masks the conserved caspase-3 cleavage site present at the tip of the stalk region from host cell caspase-3 interaction and cleavage. By incubation with primer-length ssRNAs, we also obtained the crystal structure of CCHFV N in its monomeric form, which is similar to a recently published structure. The conformational change of CCHFV N upon deoligomerization results in the exposure of the caspase-3 cleavage site and subjects CCHFV N to caspase-3 cleavage. Mutations of this cleavage site inhibit cleavage by caspase-3 and result in enhanced viral polymerase activity. Thus, cleavage of CCHFV N by host cell caspase-3 appears to be crucial for controlling viral RNA synthesis and represents an important host defense mechanism against CCHFV infection.-
dc.languageengen_US
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/-
dc.relation.ispartofJournal of Virologyen_US
dc.rightsJournal of Virology. Copyright © American Society for Microbiology.-
dc.rightsCopyright © American Society for Microbiology, [Journal of Virology, 2012, v. 86 n. 22, p. 12294-12303]-
dc.titleStructure of Crimean-Congo hemorrhagic fever virus nucleoprotein: superhelical homo-oligomers and the role of caspase-3 cleavageen_US
dc.typeArticleen_US
dc.identifier.emailHao, Q: qhao@hku.hken_US
dc.identifier.emailMirazimi, A: ali.mirazimi@smi.seen_US
dc.identifier.emailKotaka, M: masayo@hku.hk-
dc.identifier.authorityHao, Q=rp01332en_US
dc.identifier.authorityKotaka, M=rp00293en_US
dc.identifier.doi10.1128/JVI.01627-12-
dc.identifier.pmid22951837-
dc.identifier.pmcidPMC3486442-
dc.identifier.scopuseid_2-s2.0-84869134254-
dc.identifier.hkuros209502en_US
dc.identifier.volume86en_US
dc.identifier.issue22-
dc.identifier.spage12294-
dc.identifier.epage12303-
dc.identifier.isiWOS:000310356400030-
dc.publisher.placeUnited States-

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