RT Journal Article
T1 Role of severe acute respiratory syndrome Coronavirus Viroporins E, 3a, and 8a in replication and pathogenesis
A1 Castaño-Rodriguez, Carlos
A1 Honrubia, José M.
A1 Gutiérrez-Álvarez, Javier
A1 DeDiego, Marta L.
A1 Nieto-Torres, Jose Luis
A1 Jimenez-Guardeño, Jose Manuel
A1 Regla-Nava, Jose Angel
A1 Fernandez-Delgado, Raul
A1 Verdiá-Báguena, Carmina
A1 Queralt-Martín, María
A1 Kochan, Grazyna
A1 Perlman, Stanley
A1 Aguilella, Vicente M
A1 Sola, Isabel
A1 Enjuanes, Luis
K1 Virus - Reproducción
K1 Infecciones por coronavirus
K1 Microorganismos patógenos
AB 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.
PB American Society for Microbiology
YR 2018
FD 2018
LK https://hdl.handle.net/10630/36916
UL https://hdl.handle.net/10630/36916
LA eng
NO 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 MKochan 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 9:10.1128/mbio.02325-17. https://doi.org/10.1128/mbio.02325-17
NO his work was supported by grants from the Government of Spain (BIO2013-42869-R and BIO2016-75549-R AEI/FEDER, UE), the European Zoonotic Anticipation and Preparedness Initiative (ZAPI) (IMI_JU_115760), and the U.S. National Institutes of Health (NIH) (0258-3413/HHSN266200700010C awarded to L.E., 2P01AI060699 awarded to L.E. and S.P., and R01 AI129269 awarded to S.P.). V.M.A. and M.Q.M. are grateful for the support of the Government of Spain (FIS2013-40473-P and FIS2016-75257-P AEI/FEDER, UE) and Universitat Jaume I (P1.1B2015-28). C.C.R. received a contract from Fundación La Caixa.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026