RESUMO
Each year, the Brazilian Society for Virology promotes a national meeting during the second semester of the year. In October 2022, the 33rd meeting took place at Arraial da Ajuda, Porto Seguro, Bahia, in-person:.this was the first in-person meeting since 2019, as the 2020 and 2021 events occurred online due to the issues imposed by COVID-19. It was a great pleasure for the whole audience to return to an in-person event, which certainly improved the interactions between the attendees in all ways. As usual, the meeting involved massive participation of undergraduate, graduate, and postdoc students, and several noteworthy international researchers were present. During five afternoons and evenings, attendees could discuss and learn about the most recent data presented by distinguished scientists from Brazil and other countries. In addition, young virology researchers from all levels could present their latest results as oral presentations and posters. The meeting covered all virology areas, with conferences and roundtables about human, veterinary, fundamental, environmental, invertebrate, and plant virology. The costs associated with attending the in-person event caused a slight reduction in the number of attendees compared to the two online events. However, even with this issue, the attendance was impressive. The meeting successfully achieved its most important goals: inspiring young and senior scientists and discussing high-quality, up-to-date virology research.
Assuntos
COVID-19 , Humanos , Brasil , Sociedades Científicas , VirologiaRESUMO
Coronaviruses are the etiologic agents of several diseases. Coronaviruses of critical medical importance are characterized by highly inflammatory pathophysiology, involving severe pulmonary impairment and infection of multiple cell types within the body. Here, we discuss the interplay between coronaviruses and autophagy regarding virus life cycle, cell resistance, and inflammation, highlighting distinct mechanisms by which autophagy restrains inflammatory responses, especially those involved in coronavirus pathogenesis. We also address different autophagy modulators available and the rationale for drug repurposing as an attractive adjunctive therapy. We focused on pharmaceuticals being tested in clinical trials with distinct mechanisms but with autophagy as a common target. These autophagy modulators act in cell resistance to virus infection and immunomodulation, providing a double-strike to prevent or treat severe disease development and death from coronaviruses diseases.
Assuntos
Infecções por Coronavirus , Coronavirus , Autofagia/fisiologia , Coronavirus/fisiologia , Infecções por Coronavirus/patologia , Humanos , Inflamação , Carga Viral , Replicação Viral/fisiologiaRESUMO
The Brazilian Society of Virology has been organizing annual meetings for 32 years now. The 32nd annual meeting, which occurred in 2021, was once again an online meeting in consequence of the issues imposed by COVID-19, even with the vaccination advances. As in the 2020 meeting, the number of attendees was high, with considerable participation by undergraduate, graduate, and postdoc students. Distinguished scientists from different countries offered high-quality conferences, and oral presentation sessions were presented by young scientists showing their newest research results. For almost five hours a day during five days, attendees discussed high-quality science related to all areas of virology. Even with the difficulties imposed by another pandemic year, the 32nd SBV annual meeting achieved its most important goal-to inspire young scientists and discuss high-quality virology research.
Assuntos
COVID-19 , Brasil/epidemiologia , HumanosRESUMO
Current guidelines for patient isolation in COVID-19 cases recommend a symptom-based approach, averting the use of control real-time reverse transcription PCR (rRT-PCR) testing. However, we hypothesized that patients with persistently positive results by RT-PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be potentially infectious for a prolonged time, even if immunocompetent and asymptomatic, which would demand a longer social isolation period than presently recommended. To test this hypothesis, 72 samples from 51 mildly symptomatic immunocompetent patients with long-lasting positive rRT-PCR results for SARS-CoV-2 were tested for their infectiousness in cell culture. The serological response of samples from those patients and virus genomic integrity were also analyzed. Infectious viruses were successfully isolated from 34.38% (22/64) of nasopharynx samples obtained 14 days or longer after symptom onset. Indeed, we observed successful virus isolation up to 128 days. Complete SARS-COV-2 genome integrity was demonstrated, suggesting the presence of replication-competent viruses. No correlation was found between the isolation of infectious viruses and rRT-PCR cycle threshold values or the humoral immune response. These findings call attention to the need to review current isolation guidelines, particularly in scenarios involving high-risk individuals. IMPORTANCE In this study, we evaluated mildly symptomatic immunocompetent patients with long-lasting positive rRT-PCR results for SARS-CoV-2. Infectious viruses were successfully isolated in cell cultures from nasopharynx samples obtained 14 days or longer after symptom onset. Indeed, we observed successful virus isolation for up to 128 days. Moreover, SARS-CoV-2 genome integrity was demonstrated by sequencing, suggesting the presence of replication-competent viruses. These data point out the risk of continuous SARS-CoV-2 transmission from patients with prolonged detection of SARS-CoV-2 in the upper respiratory tract, which has important implications for current precaution guidelines, particularly in settings where vulnerable individuals may be exposed (e.g., nursing homes and hospitals).
Assuntos
Teste de Ácido Nucleico para COVID-19/métodos , COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Adulto , COVID-19/diagnóstico , Feminino , Genoma Viral , Genômica , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Isolamento de Pacientes , Carga Viral , Proteínas Virais/isolamento & purificação , Eliminação de Partículas ViraisRESUMO
The integral membrane protein ATG9A plays a key role in autophagy. It displays a broad intracellular distribution and is present in numerous compartments, including the plasma membrane (PM). The reasons for the distribution of ATG9A to the PM and its role at the PM are not understood. Here, we show that ATG9A organizes, in concert with IQGAP1, components of the ESCRT system and uncover cooperation between ATG9A, IQGAP1 and ESCRTs in protection from PM damage. ESCRTs and ATG9A phenocopied each other in protection against PM injury. ATG9A knockouts sensitized the PM to permeabilization by a broad spectrum of microbial and endogenous agents, including gasdermin, MLKL and the MLKL-like action of coronavirus ORF3a. Thus, ATG9A engages IQGAP1 and the ESCRT system to maintain PM integrity.
Assuntos
Proteínas Relacionadas à Autofagia/metabolismo , Membrana Celular/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Autofagossomos/metabolismo , Proteínas Relacionadas à Autofagia/genética , Células HEK293 , Células HeLa , Humanos , Immunoblotting , Imunoprecipitação , Proteínas de Membrana/genética , Microscopia Confocal , Transporte Proteico/fisiologia , Proteínas de Transporte Vesicular/genéticaRESUMO
Autophagy is a homeostatic process with multiple functions in mammalian cells. Here, we show that mammalian Atg8 proteins (mAtg8s) and the autophagy regulator IRGM control TFEB, a transcriptional activator of the lysosomal system. IRGM directly interacted with TFEB and promoted the nuclear translocation of TFEB. An mAtg8 partner of IRGM, GABARAP, interacted with TFEB. Deletion of all mAtg8s or GABARAPs affected the global transcriptional response to starvation and downregulated subsets of TFEB targets. IRGM and GABARAPs countered the action of mTOR as a negative regulator of TFEB. This was suppressed by constitutively active RagB, an activator of mTOR. Infection of macrophages with the membrane-permeabilizing microbe Mycobacterium tuberculosis or infection of target cells by HIV elicited TFEB activation in an IRGM-dependent manner. Thus, IRGM and its interactors mAtg8s close a loop between the autophagosomal pathway and the control of lysosomal biogenesis by TFEB, thus ensuring coordinated activation of the two systems that eventually merge during autophagy.
Assuntos
Família da Proteína 8 Relacionada à Autofagia/fisiologia , Autofagia/fisiologia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Proteínas de Ligação ao GTP/fisiologia , Serina-Treonina Quinases TOR/metabolismo , Calcineurina/metabolismo , Linhagem Celular , Núcleo Celular/metabolismo , Células HEK293 , Células HeLa , Humanos , Lisossomos/fisiologia , Transporte Proteico , Proteínas Qa-SNARE/metabolismoRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.