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1.
Methods Mol Biol ; 2568: 147-163, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36227567

RESUMO

Small angle X-ray scattering (SAXS) has been widely applied as an enabling integrative technique for comprehensive analysis of the structure of biomacromolecules by multiple, complementary techniques in solution. SAXS in combination with computational modeling can be a powerful strategy bridging the secondary and 3D structural analysis of large RNAs, including the long noncoding RNAs (lncRNA). Here, we outline the major procedures and techniques in the combined use of SAXS and computational modeling for 3D structural characterization of a lncRNA, the subgenomic flaviviral RNA from Zika virus. lncRNA production and purification, RNA buffer and sample preparation for SAXS experiments, SAXS data collection and analysis, SAXS-aided RNA 3D structure prediction, and computational modeling are described.


Assuntos
RNA Longo não Codificante , Infecção por Zika virus , Zika virus , Simulação por Computador , Humanos , Modelos Moleculares , Conformação de Ácido Nucleico , Espalhamento a Baixo Ângulo , Difração de Raios X , Raios X , Zika virus/genética
2.
Braz. j. biol ; 83: e240118, 2023. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1278559

RESUMO

Abstract For many centuries human populations have been suffering and trying to fight with disease-bearing mosquitoes. Emerging and reemerging diseases such as Dengue, Zika, and Chikungunya affect billions of people around the world and recently has been appealing to control with chemical pesticides. Malathion (MT) is one of the main pesticides used against mosquitoes, the vectors of these diseases. This study aimed to assess cytotoxicity and mutagenicity of the malathion for the bioindicator Allium cepa L. using a multivariate and integrative approach. Moreover, an appendix table was compiled with all available literature of insecticides assessed by the Allium cepa system to support our discussion. Exposures during 48h to 0.5 mg mL-1 and 1.0 mg mL-1 MT were compared to the negative control (distilled water) and positive control (MMS solution at 10 mg L-1). The presence of chromosomal aberrations, micronuclei frequency, and mitotic index abnormalities was evaluated. Anaphase bridges were the alterations with higher incidence and presented a significantly elevated rate in the concentration of 0.5 mg mL-1, including when compared to the positive control. The integrative discriminant analysis summarizes that MT in assessed concentrations presented effects like the positive control, corroborating its potential of toxicity to DNA. Therefore, it is concluded that MT in its pure composition and in realistic concentrations used, has genotoxic potential in the biological assessment of A. cepa cells. The multivariate integrative analysis was fundamental to show a whole response of all data, providing a global view of the effect of MT on DNA.


Resumo Por muitos séculos, as populações humanas sofrem e tentam combater os mosquitos transmissores de doenças. Doenças emergentes e reemergentes como Dengue, Zika e Chikungunya afetam bilhões de pessoas em todo o mundo e, recentemente, vem apelando ao controle com pesticidas químicos. O Malation (MT) é um dos principais pesticidas usados ​​contra mosquitos, vetores dessas doenças. O objetivo deste estudo foi avaliar a citotoxicidade e a mutagenicidade do MT para o bioindicador Allium cepa L. usando uma abordagem multivariada e integrativa. Além disso, uma tabela suplementar foi compilada com toda a literatura disponível de inseticidas avaliada pelo sistema Allium cepa para apoiar nossa discussão. Exposições ao MT durante 48h a 0,5 mg mL-1 e 1,0 mg mL-1 foram comparadas a um controle negativo (água destilada) e um controle positivo (10 mg L-1 de MMS). Foram avaliadas a presença de aberrações cromossômicas, frequência de micronúcleos e anormalidades no índice mitótico. As pontes anafásicas foram as alterações com maior incidência e apresentaram uma taxa significativamente elevada na concentração de 0,5 mg mL-1, inclusive quando comparadas ao controle positivo. A análise discriminante integrativa resume que o MT nas concentrações avaliadas apresentou efeitos semelhantes ao controle positivo, corroborando seu potencial de toxicidade para o DNA. Portanto, conclui-se que o MT, em sua composição pura e nas concentrações realistas utilizadas, possui potencial genotóxico na avaliação biológica de células de A. cepa. A análise integrativa multivariada foi fundamental para mostrar uma resposta completa de todos os dados, fornecendo uma visão global do efeito da MT no DNA.


Assuntos
Humanos , Animais , Zika virus , Infecção por Zika virus , Inseticidas/toxicidade , Dano ao DNA , Aberrações Cromossômicas , Raízes de Plantas , Cebolas , Mosquitos Vetores , Malation/toxicidade , Índice Mitótico
3.
Methods Mol Biol ; 2575: 305-321, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36301483

RESUMO

Infectious agents often challenge therapeutics, from antibiotics resistance to antigenic variability affecting inoculation measures. Over the last decades, genome sequencing arose as an important ally to address such challenges. In bacterial infection, whole-genome-sequencing (WGS) supports tracking pathogenic alterations affecting the human microbiome. In viral infection, the analysis of the relevant sequence of nucleotides helps with determining historical variants of a virus and elucidates details about infection clusters and their distribution. Additionally, genome sequencing is now an important step in inoculation protocols, isolating target genes to design more robust immunisation assays. Ultimately, genetic engineering has empowered repurposing at scale, allowing long-lasting repeating clinical trials to be automated within a much shorter time-frame, by adjusting existing protocols. This is particularly important during sanitary emergencies as the ones caused by the 2014 West African Ebola outbreak, the Zika virus rapid spread in both South and North America in 2015, followed by Asia in 2016, and the pandemic caused by the SARS-CoV-2, which has infected more than 187 million people and caused more than 4 million deaths, worldwide, as per July 2021 statistics. In this scenery, this chapter presents a novel fully automated strategy to handle antigenic variability in immunisation protocols. The methodology comprises of two major steps (1) nanopore sequencing of infectious agent variants - the focus is on the SARS-CoV-2 and its variants; followed by (2) mRNA vector design for immunotherapy. This chapter presents the nanopore sequencing step and Chapter 17 introduces a protocol for mRNA vector design.


Assuntos
COVID-19 , Sequenciamento por Nanoporos , Infecção por Zika virus , Zika virus , Humanos , SARS-CoV-2/genética , COVID-19/prevenção & controle , Imunização , Variação Antigênica , RNA Mensageiro , Zika virus/genética
4.
Med Educ Online ; 28(1): 2139657, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36331873

RESUMO

INTRODUCTION: Over the past two years, coronavirus disease (COVID-19) has greatly altered medical student education as well as daily life. Medical schools across the world were disrupted and had to immediately adapt the educational experience to the online environment in order to continue the delivery of quality medical education. However, COVID-19 was not the only recent pandemic. This posed the question, were similar disruptions and adaptations also seen in recent past pandemics such as Severe Acute Respiratory Syndrome (SARS) or Middle East Respiratory Syndrome (MERS) that could have prepared medical educators for COVID-19? This scoping review investigated the educational and personal impact of recent pandemics on medical students. METHODS: This review followed the PRISMA-ScR guidelines for scoping reviews. Nine databases including PubMed, ERIC, and EMBASE were systematically searched using keywords and subject headings related to medical students and SARS, H1N1, MERS, Ebola, Zika, and COVID-19. Studies were limited to research studies published between 2000 and 2020 and in English. Based on exclusion and inclusion criteria, all studies were independently screened by two reviewers first by the title/abstract and then via full text. Data were extracted from the included studies and analyzed qualitatively using thematic analysis. RESULTS: A total of 174 studies fit the criteria. Seven major themes emerged from those studies: educational adaptations and online modifications, knowledge and attitudes of students, mental wellness of students, student involvement and use of telehealth, student vaccination, physical wellness of students, and stigma. CONCLUSION: This review provided insights into how medical students were affected by recent pandemics and their perceptions of pivoting to online education, mental health, and knowledge of the diseases. Additionally, this review showcases the various educational adaptations that emerged uniquely during the COVID-19 pandemic, such as telehealth services or video conferencing tools, that can be utilized in a post-pandemic environment.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , Estudantes de Medicina , Infecção por Zika virus , Zika virus , Humanos , COVID-19/epidemiologia , Pandemias , SARS-CoV-2
5.
Acta Trop ; 237: 106724, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36270381

RESUMO

The risk of autochthonous transmission of Zika virus (ZIKV) in Europe greatly depends on the capacity of Aedes albopictus to transmit ZIKV. Experimental studies of the vector competence of European populations of this invasive mosquito species provided contrasting results, that may suggest differences between mosquito populations in ZIKV competence and/or differences in the methodological procedures used on the experimental studies. We systematically reviewed published studies of experimental mosquito infections and show that differences detected in the infection and transmission rates of Ae. albopictus are mostly due to differences between studies in the temperature, the viral load used to inoculate mosquitoes, and the number of days post-exposure (dpe) to the virus at which mosquitoes were analysed. In particular, the proportion of infected mosquitoes was affected by the viral load inoculated and the dpe, whereas the transmission rate was influenced by the viral load and temperature. Thus, the methodological differences used in these studies greatly affect the conclusions obtained regarding the role of Ae. albopictus in Europe as a competent vector for ZIKV and its epidemiological relevance.


Assuntos
Aedes , Infecção por Zika virus , Zika virus , Animais , Mosquitos Vetores , Saliva
6.
Acta Trop ; 237: 106736, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36374844

RESUMO

Genetic and phylogenetic studies indicated that Zika virus (ZIKV) has evolved into 2 major lineages, the African and Asian. However, ZIKV has been described as a single serotype. This study aimed at assessing the cross-neutralization between ZIKV African and Asian lineages strains. Sixthy-five samples collected in 2007 and 30 samples collected from the same subjects in 2011/2012 in West Africa and positive to neutralizing antibody against ZIKV MR-766 strain (African lineage) were tested against ZIKV H/PF/2013 strain (Asian lineage) by microneutralization assay. All samples showing neutralizing antibodies against MR-766 strain showed also neutralizing activity against H/PF/2013 strain, although with lower titers. This is consistent with about 120 amino acid differences between the two strains. Despite differences in the magnitude of neutralizing activity against different ZIKV strains, all samples showed neutralizing antibody titers considered to be protective.


Assuntos
Infecção por Zika virus , Zika virus , Humanos , Zika virus/genética , Soros Imunes , Filogenia , Anticorpos Antivirais , Anticorpos Neutralizantes
7.
J Virol Methods ; 311: 114638, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36328081

RESUMO

The genus Flavivirus in the Flaviridae contains arthropod born viruses associated with high public health burdens like Zika, Dengue or Yellow fever. Saboya virus (SABV) is an understudied flavivirus grouping in the same genetic sub-group as Yellow Fever Virus (YFV) together with Sepik virus (SEPV) and Wesselbron virus (WSLV). Flavivirus infections are characterized by non-specific clinical presentations resulting in a high risk of misdiagnosis. SABV virus has been shown to circulate in the Sahelian zone and in central Africa. To study this virus we a qRT-PCR system based on TaqMan chemistry was developed to allow rapid and specific detection of SABV. The SABV assay was evaluated on available SABV isolates and others flaviviruses (DENV, ZIKV, YFV, WNV, KEDV). The system reliably detected all used SABV strains without cross amplification of other flaviviruses. In term of sensitivity the SABV assay detect up to 40.25 copies of SABV standard DNA molecule per ul. This system can be easily added to the available panel of arboviruses detection assays as a reliable tool to study virus prevalence in human, vertebrate and insect-vector samples.


Assuntos
Vírus da Dengue , Flavivirus , Febre Amarela , Infecção por Zika virus , Zika virus , Humanos , Flavivirus/genética , Febre Amarela/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real , Vírus da Febre Amarela/genética
8.
Colloids Surf B Biointerfaces ; 221: 112984, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36371925

RESUMO

We report the development of a new nanostructured electrochemical immunosensing platform for the detection of the Zika virus envelope protein (EP-ZIKV). For this, quantum dots (QDs) were explored in combination with screen-printed carbon electrodes (SPCEs) functionalized with a conductor polymeric film, formed from 2-(1H-pyrrol-1-yl)ethanamine (Pyam), and anti-EP DIII ZIKV antibodies. Carboxylated CdTe QDs were synthesized, characterized by optical and structural techniques, and covalently immobilized onto the SPCE/PPyam surface. Then, anti-EP ZIKV antibodies were also covalently conjugated to QDs. All stages of platform assembly were evaluated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The detection of EP-ZIKV was performed by differential pulse voltammetry (DPV). Results indicated that QDs were efficiently immobilized, and did not show oxidation, under the conditions evaluated, for at least 7 months. Anti-EP ZIKV antibodies were effectively immobilized on the PPyam/QDs surface, even after 2 months of electrode storage. The platform enabled the detection of EP-ZIKV with high sensitivity using minimal sample volumes (LOD = 0.1 ng mL-1 and LOQ = 0.4 ng mL-1). The platform was also able to detect EP-ZIKV in spiked serum samples. Moreover, the platform showed specificity, not detecting the EP-DENV 3 nor a mixture of four DENV serotypes antigens. Thus, the proposed combination favored the development of a sensitive immunosensing platform, promising for the detection of Zika in the viremic phase, which also holds potential for transposition to other arboviruses.


Assuntos
Técnicas Biossensoriais , Compostos de Cádmio , Pontos Quânticos , Infecção por Zika virus , Zika virus , Humanos , Pontos Quânticos/química , Zika virus/metabolismo , Infecção por Zika virus/diagnóstico , Compostos de Cádmio/química , Telúrio/química , Técnicas Biossensoriais/métodos , Biomarcadores/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-36411078

RESUMO

BACKGROUND AND OBJECTIVES: Recent outbreaks of Zika virus (ZIKV) in South and Central America have highlighted significant neurologic side effects. Concurrence with the inflammatory neuropathy Guillain-Barré syndrome (GBS) is observed in 1:4,000 ZIKV cases. Whether the neurologic symptoms of ZIKV infection are immune mediated is unclear. We used rodent and human live cellular models to screen for anti-peripheral nerve reactive IgG and IgM autoantibodies in the sera of patients with ZIKV with and without GBS. METHODS: In this study, 52 patients with ZIKV-GBS were compared with 134 ZIKV-infected patients without GBS and 91 non-ZIKV controls. Positive sera were taken forward for target identification by immunoprecipitation and mass spectrometry, and candidate antigens were validated by ELISA and cell-based assays. Autoantibody reactions against glycolipid antigens were also screened on an array. RESULTS: Overall, IgG antibody reactivities to rat Schwann cells (SCs) (6.5%) and myelinated cocultures (9.6%) were significantly higher, albeit infrequent, in the ZIKV-GBS group compared with all controls. IgM antibody immunoreactivity to dorsal root ganglia neurones (32.3%) and SCs (19.4%) was more frequently observed in the ZIKV-GBS group compared with other controls, whereas IgM reactivity to cocultures was as common in ZIKV and non-ZIKV sera. Strong axonal-binding ZIKV-GBS serum IgG antibodies from 1 patient were confirmed to react with neurofascin 155 and 186. Serum from a ZIKV-infected patient without GBS displayed strong myelin-binding and putative antilipid antigen reaction characteristics. There was, however, no significant association of ZIKV-GBS with any known antiglycolipid antibodies. DISCUSSION: Autoantibody responses in ZIKV-GBS target heterogeneous peripheral nerve antigens suggesting heterogeneity of the humoral immune response despite a common prodromal infection.


Assuntos
Síndrome de Guillain-Barré , Infecção por Zika virus , Zika virus , Humanos , Animais , Ratos , Infecção por Zika virus/complicações , Infecção por Zika virus/epidemiologia , Síndrome de Guillain-Barré/diagnóstico , Imunoglobulina M , Imunoglobulina G , Autoanticorpos
10.
Bioorg Chem ; 130: 106265, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36417826

RESUMO

Zika virus (ZIKV) infection could cause severe neurological complications such as neonatal microcephaly, Guillain-Barré syndrome, and myelitis in adults. No vaccine or therapeutic drug is available for prevention and control of ZIKV infection yet. Based on previously reported anti-ZIKV hit compound 1, a series of novel N-benzoyl or phenylsulfonyl substituted 2-(piperazin-1-yl)methyl-benzonitrile (PMBN) derivatives was designed, synthesized, and investigated for the antiviral activity against ZIKV replication in different cell-based phenotypic assays. The results indicated that N-phenylsulfonyl-PMBN derivative 24 displayed the comparable antiviral activity and higher oral availability than hit compound 1. Meanwhile, mechanism of action study confirmed that compound 24 acts on the early entry stage of ZIKV life cycle. The identification of this new ZIKV entry inhibitor chemotype provided a promising lead for further optimization to develop new drug for ZIKV infection.


Assuntos
Inibidores da Fusão de HIV , Infecção por Zika virus , Zika virus , Humanos , Infecção por Zika virus/tratamento farmacológico , Internalização do Vírus , Antivirais/farmacologia , Antivirais/uso terapêutico , Piperazina/uso terapêutico
11.
Adv Neurobiol ; 29: 449-477, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36255684

RESUMO

A number of viruses that have caused wide spread concern e.g. Ebola, Zika, and SARS-CoV2 (severe acute respiratory syndrome coronavirus 2 also known as COVID 19) have at various times, become newsworthy as a result of being newly discovered, mutations enabling them to more efficiently infect humans or modern modes of transportation moving them to areas with naive, susceptible populations. As more is learned about the mechanisms whereby these pathogens enter human cells it has become increasingly evident that carbohydrates expressed on the surface of either target cells or the pathogens themselves are essential. Variability in carbohydrate structures as well as the presence of carbohydrate binding receptors (lectins) provides a plethora of potential binding interactions by which infection of cells can occur. Identification of specific lipid- or protein-associated carbohydrates essential for infection provides support for research being done to develop carbohydrate related inhibitors of those interactions. This chapter (1) discusses scenarios for how carbohydrates affect the ability of specific infectious agents to interact with neural cells, (2) gives examples of problems that may result from development of antibodies to carbohydrate antigens found on pathogens that are similar to epitopes expressed on mammalian cells, and (3) provides examples of approaches either in use or under consideration for translational uses of this information.


Assuntos
COVID-19 , Infecção por Zika virus , Zika virus , Animais , Humanos , SARS-CoV-2 , RNA Viral , Carboidratos/química , Sítios de Ligação , Epitopos , Lectinas , Lipídeos , Infecção por Zika virus/tratamento farmacológico , Mamíferos
12.
Gigascience ; 112022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329618

RESUMO

Vector-borne diseases are responsible for more than 17% of human cases of infectious diseases. In most situations, effective control of debilitating and deadly vector-bone diseases (VBDs), such as malaria, dengue, chikungunya, yellow fever, Zika and Chagas requires up-to-date, robust and comprehensive information on the presence, diversity, ecology, bionomics and geographic spread of the organisms that carry and transmit the infectious agents. Huge gaps exist in the information related to these vectors, creating an essential need for campaigns to mobilise and share data. The publication of data papers is an effective tool for overcoming this challenge. These peer-reviewed articles provide scholarly credit for researchers whose vital work of assembling and publishing well-described, properly-formatted datasets often fails to receive appropriate recognition. To address this, GigaScience's sister journal GigaByte partnered with the Global Biodiversity Information Facility (GBIF) to publish a series of data papers, with support from the Special Programme for Research and Training in Tropical Diseases (TDR), hosted by the World Health Organisation (WHO). Here we outline the initial results of this targeted approach to sharing data and describe its importance for controlling VBDs and improving public health.


Assuntos
Doenças Transmissíveis , Infecção por Zika virus , Zika virus , Animais , Humanos , Vetores de Doenças , Editoração
13.
Front Public Health ; 10: 919780, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36419988

RESUMO

Personality is known to affect compliance with health-protective behaviors and it has been shown that effective public health messaging can be informed by an understanding of that relationship. Thus, we aimed to evaluate the role personality might play in implementing personal protective measures (PPMs) that can prevent mosquito-borne diseases. This is the first mosquito-related knowledge, attitudes, and practices (KAP) study to incorporate a measure of personality using the Big Five: openness, conscientiousness, extraversion, agreeableness, and neuroticism. KAP studies in Gulf-coast and Mexican border-states in the U.S. are few. Ours is only the second KAP study to take place in Texas despite known local transmission and established mosquito populations capable of transmitting dengue, zika, chikungunya, and West Nile viruses. The KAP survey was administered in three neighborhoods in San Antonio, a large, Hispanic-majority, urban city that is segregated economically and ecologically. We found that openness, agreeableness, and extraversion predicted certain attitudes and PPMs, and that KAP and personality measures did not differ along ethnic or neighborhood lines. Perceptions toward the city's role in mosquito control and education was an important factor in predicting PPMs, suggesting that city culture (attitudes common throughout the city as opposed to attitudes differing by ethnicity and neighborhood) may be most salient in developing public health messaging in San Antonio.


Assuntos
Culicidae , Doenças Transmitidas por Vetores , Infecção por Zika virus , Zika virus , Animais , Texas , Controle de Mosquitos , Personalidade , Infecção por Zika virus/prevenção & controle
14.
Genes (Basel) ; 13(11)2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36360187

RESUMO

Aedes albopictus is an indigenous primary vector of dengue and Zika viruses in China. Understanding the population spatial genetic structure, migration, and gene flow of vector species is critical to effectively preventing and controlling vector-borne diseases. The genetic variation and population structure of Ae. albopictus populations collected from 22 cities along the Yangtze River Basin were investigated with nine microsatellite loci and the mitochondrial CoxI gene. The polymorphic information content (PIC) values ranged from 0.534 to 0.871. The observed number of alleles (Na) values ranged from 5.455 to 11.455, and the effective number of alleles (Ne) values ranged from 3.106 to 4.041. The Shannon Index (I) ranged from 1.209 to 1.639. The observed heterozygosity (Ho) values ranged from 0.487 to 0.545. The FIS value ranged from 0.047 to 0.212. All Ae. albopictus populations were adequately allocated to three clades with significant genetic differences. Haplotype 2 is the most primitive molecular type and forms 26 other haplotypes after one or more site mutations. The rapid expansion of high-speed rail, aircraft routes and highways along the Yangtze River Basin have accelerated the dispersal and communication of mosquitoes, which appears to have contributed to inhibited population differentiation and promoted genetic diversity among Ae. albopictus populations.


Assuntos
Aedes , Infecção por Zika virus , Zika virus , Animais , Aedes/genética , Mosquitos Vetores/genética , Rios , Variação Genética/genética , Repetições de Microssatélites/genética , China , Genética Populacional , Zika virus/genética , Infecção por Zika virus/genética
15.
Front Immunol ; 13: 1008084, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389816

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global pandemic, resulting in great fatalities around the world. Although the antiviral roles of RNA interference (RNAi) have been well studied in plants, nematodes and insects, the antiviral roles of RNAi in mammalians are still debating as RNAi effect is suspected to be suppressed by interferon (IFN) signaling pathways in most cell types. To determine the role of RNAi in mammalian resistance to SARS-CoV-2, we studied the profiling of host small RNAs and SARS-CoV-2 virus-derived small RNAs (vsRNAs) in the early infection stages of Vero cells, an IFN-deficient cell line. We found that host microRNAs (miRNAs) were dysregulated upon SARS-CoV-2 infection, resulting in downregulation of microRNAs playing antiviral functions and upregulation of microRNAs facilitating viral proliferations. Moreover, vsRNA peaked at 22 nt at negative strand but not the positive strand of SARS-CoV-2 and formed successive Dicer-spliced pattern at both strands. Similar characteristics of vsRNAs were observed in IFN-deficient cell lines infected with Sindbis and Zika viruses. Together, these findings indicate that host cell may deploy RNAi pathway to combat SARS-CoV-2 infection in IFN-deficient cells, informing the alternative antiviral strategies to be developed for patients or tissues with IFN deficiency.


Assuntos
COVID-19 , MicroRNAs , Infecção por Zika virus , Zika virus , Chlorocebus aethiops , Animais , Humanos , Células Vero , SARS-CoV-2/genética , RNA Viral/genética , COVID-19/genética , MicroRNAs/genética , Antivirais , Mamíferos
16.
BMC Pediatr ; 22(1): 669, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36404307

RESUMO

BACKGROUND: The outbreak and ongoing transmission of Zika virus provided an opportunity to strengthen essential newborn care and early childhood development systems through collaboration with the US Agency for International Development Applying Science to Strengthen and Improve Systems (USAID ASSIST). The objective was to create a system of sustainable training dissemination which improves newborn care-related quality indicators in the context of Zika. METHODS: From 2018-19, USAID ASSIST supported a series of technical assistance visits by the American Academy of Pediatrics (AAP) in four Caribbean countries to strengthen the clinical capacity in care of children potentially affected by Zika through dissemination of Essential Care for Every Baby (ECEB), teaching QI methodology, coaching visits, and development of clinical care guidelines. ECEB was adapted to emphasize physical exam findings related to Zika. The first series of workshops were facilitated by AAP technical advisors and the second series were facilitated by the newly trained local champions. Quality of care was monitored with performance indicators at 134 health facilities. RESULTS: A repeated measures (pre-post) ANOVA was conducted, revealing significant pre-post knowledge gains [F(1) = 197.9, p < 0.001] on knowledge check scores. Certain performance indicators related to ECEB practices demonstrated significant changes and midline shift on the run chart in four countries. CONCLUSION: ECEB can be adapted to incorporate important local practices, causes of neonatal morbidity and mortality, and differing healthcare system structures, which, as one part of a larger technical assistance package, leads to improved performance of health systems.


Assuntos
Infecção por Zika virus , Zika virus , Pré-Escolar , Recém-Nascido , Lactente , Humanos , Criança , Infecção por Zika virus/prevenção & controle
17.
Epidemiol Infect ; 150: e181, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36384981

RESUMO

The Guillain-Barré syndrome (GBS) has been previously associated with Zika virus infection. We analysed the data from all the patients with GBS diagnosis that were admitted to a referral hospital, in Tapachula City during the period from January 2013 to August 2016, comparing the incidence of GBS according to the temporality of the Zika outbreak in Southern Mexico. Additionally, we described the clinical and epidemiological characteristics of the GBS patients admitted before or after the Zika outbreak. We observed a sharp increase in the number of patients hospitalised due to GBS from the time the first confirmed Zika cases appeared in Mexico. Clinically we observed GBS cases before zika outbreak had more frequently history of respiratory/gastrointestinal symptoms and GBS during zika outbreak had significantly more frequently recent history of rash/conjunctivitis. Although we cannot affirm that the increased cases of GBS have a specific aetiologic association with Zika, our results suggest that this observed outbreak of in Tapachula, might have been associated to the emerging Zika epidemic, locally and suggests that rare complications associated with acute infections (such as GBS) might be useful in the surveillance systems for emerging infections.


Assuntos
Síndrome de Guillain-Barré , Infecção por Zika virus , Zika virus , Humanos , México/epidemiologia , Síndrome de Guillain-Barré/epidemiologia , Síndrome de Guillain-Barré/complicações , Infecção por Zika virus/complicações , Infecção por Zika virus/epidemiologia , Surtos de Doenças
18.
Front Cell Infect Microbiol ; 12: 1042735, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389173

RESUMO

Infection by flaviviruses leads to dramatic remodeling of the endoplasmic reticulum (ER). Viral replication occurs within virus-induced vesicular invaginations in the ER membrane. A hallmark of flavivirus infection is expansion of the ER membrane which can be observed at specific time points post infection. However, this process has not been effectively visualized in living cells throughout the course of infection at the single cell resolution. In this study, we developed a plasmid-based reporter system to monitor flavivirus infection and simultaneous virus-induced manipulation of single cells throughout the course of infection in real-time. This system requires viral protease cleavage to release an ER-anchored fluorescent protein infection reporter that is fused to a nuclear localization signal (NLS). This proteolytic cleavage allows for the translocation of the infection reporter signal to the nucleus while an ER-specific fluorescent marker remains localized in the lumen. Thus, the construct allows for the visualization of virus-dependent changes to the ER throughout the course of infection. In this study, we show that our reporter was efficiently cleaved upon the expression of multiple flavivirus proteases, including dengue virus (DENV), Zika virus (ZIKV), and yellow fever virus (YFV). We also found that the DENV protease-dependent cleavage of our ER-anchored reporter exhibited more stringent cleavage sequence specificity than what has previously been shown with biochemical assays. Using this system for long term time-lapse imaging of living cells infected with DENV, we observed nuclear translocation of the reporter signal beginning approximately 8 hours post-infection, which continued to increase throughout the time course. Interestingly, we found that increased reporter signal translocation correlated with increased ER signal intensity, suggesting a positive association between DENV infection and ER expansion in a time-dependent manner. Overall, this report demonstrates that the FlavER platform provides a useful tool for monitoring flavivirus infection and simultaneously observing virus-dependent changes to the host cell ER, allowing for study of the temporal nature of virus-host interactions.


Assuntos
Vírus da Dengue , Infecções por Flavivirus , Flavivirus , Infecção por Zika virus , Zika virus , Humanos , Vírus da Dengue/genética , Retículo Endoplasmático
19.
PLoS One ; 17(11): e0277612, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36395285

RESUMO

Mayaro virus (MAYV, Togaviridae) and Oropouche orthobunyavirus (OROV, Peribunyaviridae) are emerging enzootic arboviruses in Latin America. Outbreaks of febrile illness associated with MAYV and OROV have been reported among humans mainly in the northern region of Brazil since the 1980s, and recent data suggest these viruses have circulated also in more populated areas of western Brazil. MAYV shares mosquito vectors with yellow fever virus and it has been historically detected during yellow fever epidemics. Aiming to investigate the transmission of OROV and MAYV at the human-animal interface during a yellow fever, chikungunya and Zika outbreaks in Brazil, we conducted a retrospective molecular investigation in 810 wild and domestic animals, 106 febrile patients, and 22.931 vectors collected from 2016 to 2018 in Cuiaba and Campo Grande metropolitan regions, western Brazil. All samples tested negative for OROV and MAYV RNA by RT-qPCR. Findings presented here suggest no active circulation of MAYV and OROV in the sampled hosts. Active surveillance and retrospective investigations are instrumental approaches for the detection of cryptic and subclinical activity of enzootic arboviruses and together serve as a warning system to implement appropriate actions to prevent outbreaks.


Assuntos
Arbovírus , Orthobunyavirus , Febre Amarela , Infecção por Zika virus , Zika virus , Animais , Humanos , Brasil/epidemiologia , Estudos Retrospectivos , Orthobunyavirus/genética , Arbovírus/genética
20.
Molecules ; 27(21)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36364188

RESUMO

Mayaro virus (MAYV) is an emerging arbovirus with an increasing circulation across the Americas. In the present study, we evaluated the potential antiviral activity of the following natural compounds against MAYV and other arboviruses: Sanguinarine, (R)-Shikonin, Fisetin, Honokiol, Tanshinone IIA, and α-Mangostin. Sanguinarine and Shikonin showed significant cytotoxicity, whereas Fisetin, Honokiol, Tanshinone IIA, and α-Mangostin were well tolerated in all the cell lines tested. Honokiol and α-Mangostin treatment protected Vero-E6 cells against MAYV-induced damage and resulted in a dose-dependent reduction in viral progeny yields for each of the MAYV strains and human cell lines assessed. These compounds also reduced MAYV viral RNA replication in HeLa cells. In addition, Honokiol and α-Mangostin disrupted MAYV infection at different stages of the virus life cycle. Moreover, Honokiol and α-Mangostin decreased Una, Chikungunya, and Zika viral titers and downmodulated the expression of E1 and nsP1 viral proteins from MAYV, Una, and Chikungunya. Finally, in Honokiol- and α-Mangostin-treated HeLa cells, we observed an upregulation in the expression of type I interferon and specific interferon-stimulated genes, including IFNα, IFNß, MxA, ISG15, OAS2, MDA-5, TNFα, and IL-1ß, which may promote an antiviral cellular state. Our results indicate that Honokiol and α-Mangostin present potential broad-spectrum activity against different arboviruses through different mechanisms.


Assuntos
Alphavirus , Arbovírus , Febre de Chikungunya , Infecção por Zika virus , Zika virus , Humanos , Células HeLa , Alphavirus/genética , Replicação Viral , Antivirais/farmacologia
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