Author | Ricciardi, Simona | |
Author | Guarino, Andrea Maria | |
Author | Giaquinto, Laura | |
Author | Polishchuk, Elena V. | |
Author | Santoro, Michele | |
Author | Di Tulio, Giuseppe | |
Author | Wilson, Cathal | |
Author | Panariello, Francesco | |
Author | Soares, Vinicius C. | |
Author | Dias, Suelen S. G. | |
Author | Santos, Julia C. | |
Author | Souza, Thiago Moreno L. | |
Author | Fusco, Giovanna | |
Author | Viscardi, Maurizio | |
Author | Brandi, Sergio | |
Author | Bozza, Patrícia Torres | |
Author | Polishchuk, Roman S. | |
Author | Venditti, Rossella | |
Author | Matteis, Maria Antonieta De | |
Access date | 2022-06-09T18:48:25Z | |
Available date | 2022-06-09T18:48:25Z | |
Document date | 2022 | |
Citation | RICCIARDI, Simona et al. The role of NSP6 in the biogenesis of the SARS-CoV-2 replication organelle. Nature, p. 1-42, May 2022. | pt_BR |
ISSN | 1476-4687 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/53156 | |
Description | This is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply. | pt_BR |
Language | eng | pt_BR |
Publisher | Nature | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Biogênese | pt_BR |
Subject in Portuguese | Papel da NSP6 | pt_BR |
Subject in Portuguese | Organella | pt_BR |
Subject in Portuguese | Replicação do SARS-cOV2 | pt_BR |
Title | The role of NSP6 in the biogenesis of the SARS-CoV-2 replication organelle | pt_BR |
Type | Preprint | pt_BR |
DOI | 10.1038/s41586-022-04835-6 | pt_BR |
Abstract | SARS-CoV-2, like other coronaviruses, builds a membrane-bound replication organelle (RO) to enable RNA replication1 23 . The SARS-CoV-2 RO is composed of double membrane 24 vesicles (DMVs) tethered to the endoplasmic reticulum (ER) by thin membrane connectors2 25 , but the viral proteins and the host factors involved are currently unknown. 26 Here we identify the viral non-structural proteins (NSPs) that generate the SARS-CoV-2 27 RO. NSP3 and NSP4 generate the DMVs while NSP6, through oligomerization and an 28 amphipathic helix, zippers ER membranes and establishes the connectors. The 29 NSP6ΔSGF mutant, which arose independently in the α, β, γ, η, ι, and λ variants of SARS30 CoV-2, behaves as a gain-of-function mutant with a higher ER-zippering activity. We 31 identified three main roles for NSP6: to act as a filter in RO-ER communication allowing 32 lipid flow but restricting access of ER luminal proteins to the DMVs, to position and 33 organize DMV clusters, and to mediate contact with lipid droplets (LDs) via the LD34 tethering complex DFCP1-Rab18. NSP6 thus acts as an organizer of DMV clusters and can 35 provide a selective track to refurbish them with LD-derived lipids. Importantly, both 36 properly formed NSP6 connectors and LDs are required for SARS-CoV-2 replication. Our 37 findings, uncovering the biological activity of NSP6 of SARS-CoV-2 and of other 38 coronaviruses, have the potential to fuel the search for broad antiviral agents. | pt_BR |
Affilliation | Telethon Institute of Genetics and Medicine, TIGEM, Pozzuoli (Naples) Italy / Dept. Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Italy. | pt_BR |
Affilliation | Telethon Institute of Genetics and Medicine, TIGEM, Pozzuoli (Naples) Italy. | pt_BR |
Affilliation | Telethon Institute of Genetics and Medicine, TIGEM, Pozzuoli (Naples) Italy. | pt_BR |
Affilliation | Telethon Institute of Genetics and Medicine, TIGEM, Pozzuoli (Naples) Italy. | pt_BR |
Affilliation | Telethon Institute of Genetics and Medicine, TIGEM, Pozzuoli (Naples) Italy. | pt_BR |
Affilliation | Telethon Institute of Genetics and Medicine, TIGEM, Pozzuoli (Naples) Italy. | pt_BR |
Affilliation | Telethon Institute of Genetics and Medicine, TIGEM, Pozzuoli (Naples) Italy. | pt_BR |
Affilliation | Telethon Institute of Genetics and Medicine, TIGEM, Pozzuoli (Naples) Italy. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Programa de Imunologia e Inflamação. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnologico em Saúde. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Inovação em Doenças de Populações Negligenciadas. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Istituto Zooprofilattico Sperimentale del Mezzogiorno. 80055 Portici (Naples). Italy. | pt_BR |
Affilliation | Istituto Zooprofilattico Sperimentale del Mezzogiorno. 80055 Portici (Naples). Italy. | pt_BR |
Affilliation | Istituto Zooprofilattico Sperimentale del Mezzogiorno. 80055 Portici (Naples). Italy. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Telethon Institute of Genetics and Medicine, TIGEM, Pozzuoli (Naples) Italy. | pt_BR |
Affilliation | Telethon Institute of Genetics and Medicine, TIGEM, Pozzuoli (Naples) Italy / Dept. Molecular Medicine and Medical Biotechnology, University of Naples Federico II. Italy. | pt_BR |
Affilliation | Telethon Institute of Genetics and Medicine, TIGEM, Pozzuoli (Naples) Italy / Dept. Molecular Medicine and Medical Biotechnology, University of Naples Federico II. Italy. | pt_BR |
Subject | Role of NSP6 | pt_BR |
Subject | Biogenesis | pt_BR |
Subject | Replication organelle | pt_BR |
Subject | SARS-CoV-2 | pt_BR |