The role of NSP6 in the biogenesis of the SARS-CoV-2 replication organelle
by Simona Ricciardi et al.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.
Field validation of the performance of paper-based tests for the detection of the Zika and chikungunya viruses in serum samples
by Margot Karlikow et al.In low-resource settings, resilience to infectious disease outbreaks can be hindered by limited access to diagnostic tests. Here we report the results of double-blinded studies of the performance of paper-based diagnostic tests for the Zika and chikungunya viruses in a field setting in Latin America. The tests involved a cell-free expression system relying on isothermal amplification and toehold-switch reactions, a purpose-built portable reader and onboard software for computer vision-enabled image analysis. In patients suspected of infection, the accuracies and sensitivities of the tests for the Zika and chikungunya viruses were, respectively, 98.5% (95% confidence interval, 96.2–99.6%, 268 serum samples) and 98.5% (95% confidence interval, 91.7–100%, 65 serum samples) and approximately 2 aM and 5 fM (both concentrations are within clinically relevant ranges). The analytical specificities and sensitivities of the tests for cultured samples of the viruses were equivalent to those of the real-time quantitative PCR. Cell-free synthetic biology tools and companion hardware can provide de-centralized, high-capacity and low-cost diagnostics for use in low-resource settings.
Lying in wait: the resurgence of dengue virus after the Zika epidemic in Brazil
by Anderson Fernandes Brito et al.After the Zika virus (ZIKV) epidemic in the Americas in 2016, both Zika and dengue incidence declined to record lows in many countries in 2017–2018, but in 2019 dengue resurged in Brazil, causing ~2.1 million cases. In this study we use epidemiological, climatological and genomic data to investigate dengue dynamics in recent years in Brazil. First, we estimate dengue virus force of infection (FOI) and model mosquito-borne transmission suitability since the early 2000s. Our estimates reveal that DENV transmission was low in 2017–2018, despite conditions being suitable for viral spread.
Você conhece os impactos do vírus Zika sobre as famílias?
by Márcia Pinto et al.*Portuguese content* Com objetivo de avaliar como as famílias dessas crianças foram impactadas, a pesquisa Impactos econômicos e sociais do vírus Zika foi realizada no IFF-Fiocruz, hospital público federal situado no Rio de Janeiro, que atua em ensino, pesquisa e atendimento a mulheres, crianças e adolescentes.
COVID-19 en América Latina y Caribe: Determinación de prioridades en investigación y llamado a la acción
by Nicole Feune de Colombi et al.The Global Health Network (www.tghn.org) established in January 2020 a community of practice to address research on COVID-19 in low/middle-income countries.
Epidemiological and clinical characteristics of the first 557 successive patients with COVID-19 in Pernambuco state, Northeast Brazil
by Jurandy Júnior Ferraz deMagalhães et al.Follow-up household serosurvey in Northeast Brazil for Zika virus: sexual contacts of index patients have the highest risk for seropositivity
by Tereza Magalhaes et al.The Relative Risk (RR) of sexual partners being ZIKV seropositive when living with a ZIKV-seropositive index participant was significantly higher, while this was not observed among non-sexual partners of the index. For CHIKV, both sexual and non-sexual partner household members living with a CHIKV-seropositive index had a significantly higher risk of being seropositive.
PRE-PRINT: Non-permissive SARS-CoV-2 infection of neural cells in the developing human brain and neurospheres
by Carolina da S. G. Pedrosa et al.Coronavirus disease 2019 (COVID-19) was initially described as a viral infection of the respiratory tract. It is now known, however, that many other biological systems are affected, including the central nervous system (CNS). Neurological manifestations such as stroke, encephalitis, and psychiatric conditions have been reported in COVID-19 patients, but its neurotropic potential is still debated. Here, we investigate the presence of SARS-CoV-2 in the brain from an infant patient deceased from COVID-19. FULL TEXT
Zika epidemic and microcephaly in Brazil: Challenges for access to health care and promotion in three epidemic areas
by Paulo Cesar Peiter, Rafael dos Santos Pereira, Martha Cristina Nunes Moreira, Marcos Nascimento, Maria de Fatima Lobato Tavares, Vivian da Cruz Franco, José Joaquin Carvajal Cortês, Daniel de Souza Campos, Christovam BarcellosSince 2015 Brazil has experienced the social repercussions of the Zika virus epidemic, thus raising a debate about: difficulties of diagnosis; healthcare access for children with Zika Congenital Syndrome (ZCS); the search for benefits by affected families; social and gender inequalities; and a discussion on reproductive rights, among others. The objective of this article is to analyse access to specialized health services for the care of children born with ZCS in three North-eastern states of Brazil.
Psycho-Neuroendocrine-Immune Interactions in COVID-19: Potential Impacts on Mental Health
by Ícaro Raony, Camila Saggioro de Figueiredo, Pablo Pandolfo, Elizabeth Giestal-de-Araujo, Priscilla Oliveira-Silva Bomfim, Wilson SavinoCoronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The impacts of the disease may be beyond the respiratory system, also affecting mental health. Several factors may be involved in the association between COVID-19 and psychiatric outcomes, such as fear inherent in the pandemic, adverse effects of treatments, as well as financial stress, and social isolation.