The role of NSP6 in the biogenesis of the SARS-CoV-2 replication organelle

SARS-CoV-2, like other coronaviruses, builds a membrane-bound replication organelle (RO) to enable RNA replication1. The SARS-CoV-2 RO is composed of double membrane vesicles (DMVs) tethered to the endoplasmic reticulum (ER) by thin membrane connectors2, but the viral proteins and the host factors involved are currently unknown. Here we identify the viral non-structural proteins (NSPs) that generate the SARS-CoV-2 RO. NSP3 and NSP4 generate the DMVs while NSP6, through oligomerization and an amphipathic helix, zippers ER membranes and establishes the connectors. The NSP6ΔSGF mutant, which arose independently in the α, β, γ, η, ι, and λ variants of SARS-CoV-2, behaves as a gain-of-function mutant with a higher ER-zippering activity. We identified three main roles for NSP6: to act as a filter in RO-ER communication allowing lipid flow but restricting access of ER luminal proteins to the DMVs, to position and organize DMV clusters, and to mediate contact with lipid droplets (LDs) via the LD-tethering complex DFCP1-Rab18. NSP6 thus acts as an organizer of DMV clusters and can provide a selective track to refurbish them with LD-derived lipids. Importantly, both properly formed NSP6 connectors and LDs are required for SARS-CoV-2 replication. Our findings, uncovering the biological activity of NSP6 of SARS-CoV-2 and of other coronaviruses, have the potential to fuel the search for broad antiviral agents.

The invasive Asian bush mosquito Aedes japonicus found in the Netherlands can experimentally transmit Zika virus and Usutu virus

Given that Ae. japonicus can experimentally transmit arthropod-borne viruses (arboviruses) like ZIKV and USUV and is currently expanding its territories, we should consider this mosquito as a potential vector for arboviral diseases in Europe.

A literary history of Zika: Following Brazilian state responses through documents of emergency

Book chapter in Locating Zika Social Change and Governance in an Age of Mosquito Pandemics; Edited by Kevin Bardosh  

Assessing the Potential Interactions between Cellular miRNA and Arboviral Genomic RNA in the Yellow Fever Mosquito, Aedes aegypti

This study shows a broad picture of possible interactions between mosquito cellular miRNAs and the viral RNA of different genotypes/lineages of arboviruses, providing a list of mosquito cellular miRNAs candidates for experimental validations in future studies.

SuPReMe: a rapid reverse genetics method to generate clonal populations of recombinant RNA viruses

According to the authors, SuPReMe, therefore, represents an effective and promising option for the rapid generation of clonal recombinant populations of single-stranded positive-sense RNA viruses.

Structural and Functional Basis of the Fidelity of Nucleotide Selection by Flavivirus RNA-Dependent RNA Polymerases

In this article, the authors review current knowledge on motifs A-G, defined as the conserved amino-acid sequence strings shared by enzymes, and their role on the structural and mechanistic basis of the fidelity of nucleotide selection and RNA synthesis by Flavivirus RdRps.

Characterization of the Zika virus induced small RNA response in Aedes aegypti cells

Results from this study suggest that ZIKV has mechanisms to evade mosquito innate immunity and it is therefore important to understand virus-vector interactions and the implications they have on transmission.