Pós-pandemia ou a “endemização do (extra)ordinário”? Uma análise comparativa entre as experiências com a fome, Zika vírus e Covid-19 no Brasil

Lis Furlani Blanco; Jonatan Sacramento

doi:10.1590/s0104-71832021000100010

Pós-pandemia ou a “endemização do (extra)ordinário”? Uma análise comparativa entre as experiências com a fome, Zika vírus e Covid-19 no Brasil

Horizontes Antropológicos ◽

10.1590/s0104-71832021000100010 ◽

2021 ◽

Vol 27 (59) ◽

pp. 183-206

Author(s):

Lis Furlani Blanco ◽

Jonatan Sacramento

Keyword(s):

Zika Virus ◽

De Novo

Resumo Passado um ano da “chegada” do novo coronavírus no Brasil, apesar dos números de infecção não apresentarem declínio, iniciou-se um processo de retomada das atividades e adaptação ao “novo normal”. É o objetivo deste artigo mostrar como uma epidemia é construída enquanto uma emergência sanitária, quais os marcadores de sua temporalidade e, principalmente, como ela se produz em um processo de obliteração e externalização de fatores que muitas vezes são inerentes aos seus efeitos. Para tanto, recuperamos a trajetória de duas experiências “epidêmicas” anteriores, vivenciadas em território brasileiro, a fome e o Zika vírus. Mostraremos, a partir dessa comparação, que a epidemia de Covid-19 deve ser entendida levando em consideração que sua trajetória é produzida conjuntamente com outras experiências de saúde e doença. Se os significados do “novo normal” estão sendo disputados, é importante trazer à luz os processos que reproduzem cotidianamente o “normal de novo”.

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Zika virus found in brain tissue of a multiple sclerosis patient undergoing an acute disseminated encephalomyelitis-like episode

Multiple Sclerosis Journal ◽

10.1177/1352458518781992 ◽

2018 ◽

Vol 25 (3) ◽

pp. 427-430 ◽

Cited By ~ 3

Author(s):

Soniza Vieira Alves-Leon ◽

Monique da Rocha Lima ◽

Priscila Conrado Guerra Nunes ◽

Leila Maria Cardão Chimelli ◽

Kíssila Rabelo ◽

...

Keyword(s):

Multiple Sclerosis ◽

Monoclonal Antibody ◽

Brain Tissue ◽

Zika Virus ◽

De Novo ◽

Present Report ◽

Acute Disseminated Encephalomyelitis ◽

Molecular Diagnostic ◽

Histopathological Analysis ◽

Zikv Infection

Background: A range of different neurological manifestations has been reported in fetuses and adults after Zika virus (ZIKV) infection. Objective: We describe a detection of the ZIKV in the brain tissue from a multiple sclerosis (MS) patient with acute disseminated encephalomyelitis (ADEM)-like event in Rio de Janeiro, Brazil. Methods: Biological samples collected during the hospitalization were tested by serology and molecular diagnostic for various infectious agents. Histopathological analysis was performed using the anti-flavivirus group 4G2 monoclonal antibody, anti-ZIKV non-structural 1 (NS1) monoclonal antibody, and anti-CD4, CD8, and CD11b antibodies. Results: Anti-ZIKV IgM and IgG antibodies were positive in the serum and urine. A brain biopsy showed ZIKV protein in brain cells and T CD8 infiltration in brain tissue. Conclusion: Our data describe the coexistence of a recent central nervous system (CNS) ZIKV infection accompanied by a severe ADEM-like syndrome outcome in a patient with clinical history of MS. A de novo immune response concomitant with ZIKV infection might be involved in the mechanism of the ADEM-like syndrome and response to immunotherapy. The present report reinforces the importance of providing the differential diagnosis of acute episodes of MS exacerbation in an environment prone to ZIKV expression.

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Zika virus activates de novo and cross-reactive memory B cell responses in dengue-experienced donors

Science Immunology ◽

10.1126/sciimmunol.aan6809 ◽

2017 ◽

Vol 2 (14) ◽

pp. eaan6809 ◽

Cited By ~ 55

Author(s):

Thomas F. Rogers ◽

Eileen C. Goodwin ◽

Bryan Briney ◽

Devin Sok ◽

Nathan Beutler ◽

...

Keyword(s):

B Cell ◽

Zika Virus ◽

De Novo ◽

Memory B Cell ◽

Cell Responses ◽

B Cell Responses

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Mechanism of action of methotrexate against Zika virus

10.1101/481440 ◽

2018 ◽

Author(s):

Sungjun Beck ◽

Jean A. Bernatchez ◽

Zhe Zhu ◽

Michelli F. Oliveira ◽

Davey M. Smith ◽

...

Keyword(s):

Mechanism Of Action ◽

Zika Virus ◽

High Throughput Screening ◽

De Novo ◽

Virus Titer ◽

Antiviral Effect ◽

Human Neural Stem Cells ◽

Anti Cancer ◽

Infected Cells

AbstractZika virus (ZIKV), which is associated with microcephaly in infants and Guillain-Barré syndrome, reemerged as a serious public health threat in Latin America in recent years. Previous high-throughput screening (HTS) campaigns have revealed several potential hit molecules against ZIKV, including methotrexate (MTX), which is clinically used as an anti-cancer chemotherapy and anti-rheumatoid agent. We studied the mechanism of action of MTX against ZIKV in relation to its inhibition of dihydrofolate reductase (DHFR) in vitro using Vero and human neural stem cells (hNSCs). As expected, an antiviral effect for MTX against ZIKV was observed, showing up to ten-fold decrease in virus titer during MTX treatment. We also observed that addition of leucovorin (a downstream metabolite of DHFR pathway) rescued the ZIKV replication impaired by MTX treatment in ZIKV-infected cells, explaining the antiviral effect of MTX through inhibition of DHFR. We also found that addition of adenosine to ZIKV-infected cells was able to rescue ZIKV replication inhibited by MTX, suggesting that restriction of de novo synthesis adenosine triphosphate (ATP) pools suppresses viral replication. These results confirm that the DFHR pathway can be targeted to inhibit replication of ZIKV, similar to other published results showing this effect in related flaviviruses.

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Modeling Human Peripheral Myelin Fully from Pluripotent Stem Cells and Immune-mediated Neuropathy In Vitro using ZIKA Virus

10.1101/2020.05.23.112748 ◽

2020 ◽

Author(s):

Fahimeh Mirakhori ◽

Cheng-Feng Qin ◽

Zhiheng Xu

Keyword(s):

Stem Cells ◽

Pluripotent Stem Cells ◽

Zika Virus ◽

De Novo ◽

Underlying Mechanism ◽

Suitable Model ◽

Zikv Infection ◽

Compound Screening

SummaryThe generation of in vitro model of human peripheral myelin development and associated disease from human pluripotent stem cells (hPSCs) has been a challenge so far. In addition, the underlying mechanism for ZIKA virus (ZIKV) infection incurred Guillain-Barré syndrome (GBS) remains unexplored due to the lack of a suitable model. Here, we report the de novo generation of a human peripheral myelination model with competent Schwann cells (SCs). Those human SCs generated from hPSCs via compound screening were capable of forming compact myelin both in vitro and in vivo. We found ZIKV infection caused GBS-like events in vitro including myelin sheath degeneration, as well as dysregulated transcriptional profile including the activated cell death pathways and cytokine production. These effects could be partially reversed by several pharmacological inhibitors. Our model therefore provides a new and robust tool for studying the pathogenic mechanisms and developing of therapeutic strategies for related neuropathies.

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Zika Virus Dissemination from the Midgut of Aedes aegypti is Facilitated by Bloodmeal-Mediated Structural Modification of the Midgut Basal Lamina

Viruses ◽

10.3390/v11111056 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1056 ◽

Cited By ~ 7

Author(s):

Yingjun Cui ◽

DeAna G. Grant ◽

Jingyi Lin ◽

Xiudao Yu ◽

Alexander W. E. Franz

Keyword(s):

Aedes Aegypti ◽

Basal Lamina ◽

Zika Virus ◽

De Novo ◽

Mosquito Species ◽

Infected Mosquito ◽

Pathogenic Virus ◽

Complete Digestion ◽

Meal Ingestion ◽

Post Infectious

The arboviral disease cycle requires that key tissues in the arthropod vector become persistently infected with the virus. The midgut is the first organ in the mosquito that needs to be productively infected with an orally acquired virus. Following midgut infection, the virus then disseminates to secondary tissues including the salivary glands. Once these are productively infected, the mosquito is able to transmit the virus to a vertebrate host. Recently, we described the midgut dissemination pattern for chikungunya virus in Aedes aegypti. Here we assess the dissemination pattern in the same mosquito species for Zika virus (ZIKV), a human pathogenic virus belonging to the Flaviviridae. ZIKV infection of secondary tissues, indicative of dissemination from the midgut, was not observed before 72 h post infectious bloodmeal (pibm). Virion accumulation at the midgut basal lamina (BL) was only sporadic, although at 96–120 h pibm, virions were frequently observed between strands of the BL indicative of their dissemination. Our data suggest that ZIKV dissemination from the mosquito midgut occurs after digestion of the bloodmeal. Using gold-nanoparticles of 5 nm and 50 nm size, we show that meal ingestion leads to severe midgut tissue distention, causing the mesh width of the BL to remain enlarged after complete digestion of the meal. This could explain how ZIKV can exit the midgut via the BL after bloodmeal digestion. Ingestion of a subsequent, non-infectious bloodmeal five days after acquisition of an initial, dengue 4 virus containing bloodmeal resulted in an increased number of virions present in the midgut epithelium adjacent to the BL. Thus, subsequent bloodmeal ingestion by an infected mosquito may primarily stimulate de novo synthesis of virions leading to increased viral titers in the vector.

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Mechanism of Action of Methotrexate Against Zika Virus

Viruses ◽

10.3390/v11040338 ◽

2019 ◽

Vol 11 (4) ◽

pp. 338 ◽

Cited By ~ 12

Author(s):

Sungjun Beck ◽

Zhe Zhu ◽

Michelli F. Oliveira ◽

Davey M. Smith ◽

Jeremy N. Rich ◽

...

Keyword(s):

Mechanism Of Action ◽

Zika Virus ◽

High Throughput Screening ◽

De Novo ◽

Virus Titer ◽

Antiviral Effect ◽

Human Neural Stem Cells ◽

Anti Cancer ◽

Infected Cells

Zika virus (ZIKV), which is associated with microcephaly in infants and Guillain-Barré syndrome, reemerged as a serious public health threat in Latin America in recent years. Previous high-throughput screening (HTS) campaigns have revealed several potential hit molecules against ZIKV, including methotrexate (MTX), which is clinically used as an anti-cancer chemotherapy and anti-rheumatoid agent. We studied the mechanism of action of MTX against ZIKV in relation to its inhibition of dihydrofolate reductase (DHFR) in vitro using Vero and human neural stem cells (hNSCs). As expected, an antiviral effect for MTX against ZIKV was observed, showing up to 10-fold decrease in virus titer during MTX treatment. We also observed that addition of leucovorin (a downstream metabolite of DHFR pathway) rescued the ZIKV replication impaired by MTX treatment in ZIKV-infected cells, explaining the antiviral effect of MTX through inhibition of DHFR. We also found that addition of adenosine to ZIKV-infected cells was able to rescue ZIKV replication inhibited by MTX, suggesting that restriction of de novo synthesis adenosine triphosphate (ATP) pools suppresses viral replication. These results confirm that the DHFR pathway can be targeted to inhibit replication of ZIKV, similar to other published results showing this effect in related flaviviruses.

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De Novo Generation and Characterization of New Zika Virus Isolate Using Sequence Data from a Microcephaly Case

mSphere ◽

10.1128/mspheredirect.00190-17 ◽

2017 ◽

Vol 2 (3) ◽

Cited By ~ 24

Author(s):

Yin Xiang Setoh ◽

Natalie A. Prow ◽

Nias Peng ◽

Leon E. Hugo ◽

Gregor Devine ◽

...

Keyword(s):

Deep Sequencing ◽

Zika Virus ◽

De Novo ◽

Sequence Data ◽

Fetal Brain ◽

Congenital Defects ◽

Cdna Clones ◽

Adaptive Mutations ◽

Positive Strand Rna ◽

Viral Isolates

ABSTRACT Zika virus (ZIKV) has recently emerged and is the etiological agent of congenital Zika syndrome (CZS), a spectrum of congenital abnormalities arising from neural tissue infections in utero. Herein, we describe the de novo generation of a new ZIKV isolate, ZIKVNatal, using a modified circular polymerase extension reaction protocol and sequence data obtained from a ZIKV-infected fetus with microcephaly. ZIKVNatal thus has no laboratory passage history and is unequivocally associated with CZS. ZIKVNatal could be used to establish a fetal brain infection model in IFNAR−/− mice (including intrauterine growth restriction) without causing symptomatic infections in dams. ZIKVNatal was also able to be transmitted by Aedes aegypti mosquitoes. ZIKVNatal thus retains key aspects of circulating pathogenic ZIKVs and illustrates a novel methodology for obtaining an authentic functional viral isolate by using data from deep sequencing of infected tissues. IMPORTANCE The major complications of an ongoing Zika virus outbreak in the Americas and Asia are congenital defects caused by the virus’s ability to cross the placenta and infect the fetal brain. The ability to generate molecular tools to analyze viral isolates from the current outbreak is essential for furthering our understanding of how these viruses cause congenital defects. The majority of existing viral isolates and infectious cDNA clones generated from them have undergone various numbers of passages in cell culture and/or suckling mice, which is likely to result in the accumulation of adaptive mutations that may affect viral properties. The approach described herein allows rapid generation of new, fully functional Zika virus isolates directly from deep sequencing data from virus-infected tissues without the need for prior virus passaging and for the generation and propagation of full-length cDNA clones. The approach should be applicable to other medically important flaviviruses and perhaps other positive-strand RNA viruses.

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Passive immunisation of convalescent human anti-Zika plasma protects against challenge with New World Zika virus in cynomolgus macaques

npj Vaccines ◽

10.1038/s41541-020-00234-y ◽

2020 ◽

Vol 5 (1) ◽

Author(s):

Neil Berry ◽

Sarah Kempster ◽

Claire Ham ◽

Adrian Jenkins ◽

Jo Hall ◽

...

Keyword(s):

Zika Virus ◽

Vaccine Development ◽

De Novo ◽

Protective Efficacy ◽

Lymphoid Tissues ◽

Passive Immunisation ◽

Post Challenge ◽

Virus Challenge ◽

Immune Correlates ◽

Cynomolgus Macaques

Abstract Zika virus (ZIKV) causes neurological complications in susceptible individuals, highlighted in the recent South American epidemic. Natural ZIKV infection elicits host responses capable of preventing subsequent re-infection, raising expectations for effective vaccination. Defining protective immune correlates will inform viral intervention strategies, particularly vaccine development. Non-human primate (NHP) species are susceptible to ZIKV and represent models for vaccine development. The protective efficacy of a human anti-ZIKV convalescent plasma pool (16/320-14) developed as a candidate reference material for a WHO International Standard was evaluated in macaques. Convalescent plasma administered to four cynomolgus macaques (Macaca fascicularis) intra-peritoneally 24 hrs prior to sub-cutaneous challenge with 103 pfu ZIKVPRVABC59 protected against detectable infection, with absence of detectable ZIKV RNA in blood and lymphoid tissues. Passively immunised anti-ZIKV immunoglobulin administered prior to time of challenge remained present only at very low levels 42 days post-challenge. Absence of de novo antibody responses in passively immunised macaques indicate sterilising immunity compared with naïve challenge controls that exhibited active ZIKV-specific IgM and IgG responses post-challenge. Demonstration that the presence of convalescent anti-ZIKV at levels of 400 IU/mL neutralising antibody protects against virus challenge provides a scientific framework for development of anti-ZIKV vaccines and facilitates regulatory approval.

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Microcefalia e Zika Vírus: características e associações

Revista Brasileira de Medicina de Família e Comunidade ◽

10.5712/rbmfc11(38)1297 ◽

2016 ◽

Vol 11 (38) ◽

pp. 1-10

Author(s):

Cynthia Molina Bastos ◽

Otávio Pereira D'Avila ◽

Roberto Nunes Umpierre ◽

Lavínia Schuler Faccini ◽

Marcelo Rodrigues Gonçalves ◽

...

Keyword(s):

Aedes Aegypti ◽

Aedes Albopictus ◽

Zika Virus ◽

De Novo ◽

Culex Sp

Objetivo: Discutir a associação entre microcefalia e a infecção materna por Zika Vírus. A microcefalia é o tamanho da cabeça menor do que o esperado em comparação com bebês do mesmo sexo e idade. Entre as causas conhecidas, estão as infecções congênitas. O aumento de casos entre outubro e novembro de 2015 no nordeste brasileiro, que coincidiu com a presença da circulação de novo vírus no país, em maio do mesmo ano, criou a hipótese de associação entre a microcefalia e a infecção materna durante a gravidez. O Zika Vírus é um arbovírus similar ao da Febre Amarela e da Dengue, transmitido principalmente através da picada do Aedes aegypti. A provável transmissão por relação sexual e transfusão de sangue, além de outros vetores como o Aedes albopictus e possivelmente até o pernilongo (Culex sp) aumentam a necessidade de cuidados preventivos em relação à infecção. O exame para detecção viral idealmente é realizado até o quinto dia após o início dos sintomas. Sorologias ainda não são amplamente disponíveis no Brasil. Métodos: Revisão narrativa da literatura. Conclusão: A associação entre casos de microcefalia e o Zika Vírus é embasada nos relatos de relação têmporo-espacial, padrão de alterações neurológicas associado a malformações congênitas, presença do RNA viral no líquido amniótico e nos tecidos de fetos. As respostas definitivas de causalidade serão possíveis após pesquisas e disponibilidade de exames laboratoriais. As evidências até agora apoiam fortemente esta hipótese e todas as medidas preventivas devem ser estimuladas.

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