Role of Severe Acute Respiratory Syndrome Coronavirus Viroporins E, 3a, and 8a in Replication and Pathogenesis
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Otros documentos de la autoría: Castaño Rodríguez, Carlos; Honrubia, José M.; Gutiérrez-Álvarez, Javier; De Diego, Marta L.; Nieto Torres, José L.; Jiménez Guardeño, José M.; Regla Nava, José A.; Fernández Delgado, Raúl; Verdiá Báguena, Carmen; Queralt-Martín, María; Kochan, Grazyna; Perlman, Stanley; Aguilella, Vicente; Sola, Isabel; Enjuanes, Luis
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INVESTIGACIONMetadatos
Título
Role of Severe Acute Respiratory Syndrome Coronavirus Viroporins E, 3a, and 8a in Replication and PathogenesisAutoría
Fecha de publicación
2018Editor
American Society for MicrobiologyISSN
2150-7511Cita bibliográfica
Castaño-Rodriguez C, Honrubia JM, Gutiérrez-Álvarez J, DeDiego ML, Nieto-Torres JL, Jimenez-Guardeño JM, Regla-Nava JA, Fernandez-Delgado R, Verdia-Báguena C, Queralt-Martín M, Kochan G, Perlman S, Aguilella VM, Sola I, Enjuanes L. 2018. Role of severe acute respiratory syndrome coronavirus viroporins E, 3a, and 8a in replication and pathogenesis. mBio 9:e02325-17. https://doi .org/10.1128/mBio.02325-17.Tipo de documento
info:eu-repo/semantics/articleVersión de la editorial
https://mbio.asm.org/content/9/3/e02325-17Versión
info:eu-repo/semantics/publishedVersionPalabras clave / Materias
Resumen
Viroporins are viral proteins with ion channel (IC) activity that play an
important role in several processes, including virus replication and pathogenesis.
While many coronaviruses (CoVs) encode two viroporins, ... [+]
Viroporins are viral proteins with ion channel (IC) activity that play an
important role in several processes, including virus replication and pathogenesis.
While many coronaviruses (CoVs) encode two viroporins, severe acute respiratory
syndrome CoV (SARS-CoV) encodes three: proteins 3a, E, and 8a. Additionally, proteins 3a and E have a PDZ-binding motif (PBM), which can potentially bind over 400
cellular proteins which contain a PDZ domain, making them potentially important
for the control of cell function. In the present work, a comparative study of the
functional motifs included within the SARS-CoV viroporins was performed, mostly focusing on the roles of the IC and PBM of E and 3a proteins. Our results showed that
the full-length E and 3a proteins were required for maximal SARS-CoV replication
and virulence, whereas viroporin 8a had only a minor impact on these activities. A
virus missing both the E and 3a proteins was not viable, whereas the presence of either protein with a functional PBM restored virus viability. E protein IC activity and
the presence of its PBM were necessary for virulence in mice. In contrast, the presence or absence of the homologous motifs in protein 3a did not influence virus
pathogenicity. Therefore, dominance of the IC and PBM of protein E over those of
protein 3a was demonstrated in the induction of pathogenesis in mice.
IMPORTANCE Collectively, these results demonstrate key roles for the ion channel
and PBM domains in optimal virus replication and pathogenesis and suggest that
the viral viroporins and PBMs are suitable targets for antiviral therapy and for mutation in attenuated SARS-CoV vaccines. [-]
Publicado en
mBio May/June 2018 Volume 9 Issue 3 e02325-17Proyecto de investigación
(BIO2013-42869-R and BIO2016-75549-R AEI/FEDER, UE ; IMI_JU_115760 ; 0258-3413/HHSN266200700010C ; 2P01AI060699 ; R01 AI129269 ; FIS2013-40473-P and FIS2016-75257-P AEI/FEDER, UE ; (P1.1B2015-28Derechos de acceso
info:eu-repo/semantics/openAccess
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