Anti- #ganglioside #antibodies in patients with #Zika virus #infection-associated #GBS in #Brazil (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Anti-ganglioside antibodies in patients with Zika virus infection-associated Guillain-Barré Syndrome in Brazil

Juan Rivera-Correa, Isadora Cristina de Siqueira, Sabrina Mota, Mateus Santana do Rosário, Pedro Antônio Pereira de Jesus, Luiz Carlos Junior Alcantara, Joel D. Ernst, Ana Rodriguez

Published: September 17, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007695 / This is an uncorrected proof.

 

Abstract

Zika virus infection is associated with the development of Guillain-Barré syndrome (GBS), a neurological autoimmune disorder caused by immune recognition of gangliosides and other components at nerve membranes. Using a high-throughput ELISA, we have analyzed the anti-glycolipid antibody profile, including gangliosides, of plasma samples from patients with Zika infections associated or not with GBS in Salvador, Brazil. We have observed that Zika patients that develop GBS present higher levels of anti-ganglioside antibodies when compared to Zika patients without GBS. We also observed that a broad repertoire of gangliosides was targeted by both IgM and IgG anti-self antibodies in these patients. Since Zika virus infects neurons, which contain membrane gangliosides, antigen presentation of these infected cells may trigger the observed autoimmune anti-ganglioside antibodies suggesting direct infection-induced autoantibodies as a cause leading to GBS development. Collectively, our results establish a link between anti-ganglioside antibodies and Zika-associated GBS in patients.

 

Author summary

Zika virus infection can trigger the development of Guillain Barré syndrome (GBS), a neurological autoimmune disorder mediated by antibodies recognizing gangliosides in nerve membranes. Mechanisms such as molecular mimicry have been identified as a cause for GBS development in certain infections, such as Campylobacter jejuni, but the broad self reactivity observed during GBS suggests a role for alternative mechanisms. Our finding that Zika patients with GBS present higher levels of anti-ganglioside antibodies compared to uncomplicated Zika patients in Brazil points to these auto-antibodies as a trigger for GBS in these patients. These findings further support infection-induced autoantibodies as a factor contributing to GBS development, adding novel mechanisms for GBS development beyond molecular mimicry.

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Citation: Rivera-Correa J, de Siqueira IC, Mota S, do Rosário MS, Pereira de Jesus PA, Alcantara LCJ, et al. (2019) Anti-ganglioside antibodies in patients with Zika virus infection-associated Guillain-Barré Syndrome in Brazil. PLoS Negl Trop Dis 13(9): e0007695. https://doi.org/10.1371/journal.pntd.0007695

Editor: Rebecca C. Christofferson, Louisiana State University, UNITED STATES

Received: March 18, 2019; Accepted: August 7, 2019; Published: September 17, 2019

Copyright: © 2019 Rivera-Correa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files

Funding: AR and JRC received funding for this project from New York University School of Medicine Internal Funds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Zika Virus; Immunopathology; GBS; Neurology; Brazil.

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#Transgenic #Aedes aegypti #Mosquitoes Transfer #Genes into a Natural #Population (Sci Rep., abstract)

[Source: Scientific Reports, full page: (LINK). Abstract, edited.]

Transgenic Aedes aegypti Mosquitoes Transfer Genes into a Natural Population

Benjamin R. Evans, Panayiota Kotsakiozi, Andre Luis Costa-da-Silva, Rafaella Sayuri Ioshino, Luiza Garziera, Michele C. Pedrosa, Aldo Malavasi, Jair F. Virginio, Margareth L. Capurro & Jeffrey R. Powell

Scientific Reports, volume 9, Article number: 13047 (2019)

 

Abstract

In an attempt to control the mosquito-borne diseases yellow fever, dengue, chikungunya, and Zika fevers, a strain of transgenically modified Aedes aegypti mosquitoes containing a dominant lethal gene has been developed by a commercial company, Oxitec Ltd. If lethality is complete, releasing this strain should only reduce population size and not affect the genetics of the target populations. Approximately 450 thousand males of this strain were released each week for 27 months in Jacobina, Bahia, Brazil. We genotyped the release strain and the target Jacobina population before releases began for >21,000 single nucleotide polymorphisms (SNPs). Genetic sampling from the target population six, 12, and 27–30 months after releases commenced provides clear evidence that portions of the transgenic strain genome have been incorporated into the target population. Evidently, rare viable hybrid offspring between the release strain and the Jacobina population are sufficiently robust to be able to reproduce in nature. The release strain was developed using a strain originally from Cuba, then outcrossed to a Mexican population. Thus, Jacobina Ae. aegypti are now a mix of three populations. It is unclear how this may affect disease transmission or affect other efforts to control these dangerous vectors. These results highlight the importance of having in place a genetic monitoring program during such releases to detect un-anticipated outcomes.

Keywords: Genetics; Aedes aegypti; Brazil; GMOs.

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#Zika Virus #Infection and #Microcephaly: A Case-Control Study in #Brazil (Ann Glob Health, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Ann Glob Health. 2019 Aug 28;85(1). pii: 116. doi: 10.5334/aogh.2394.

Zika Virus Infection and Microcephaly: A Case-Control Study in Brazil.

Rocha SGMO1, Correia LL1, Da Cunha AJLA2, Rocha HAL1,3, Leite ÁJM1, Campos JS3, Bandeira TJPG3, Do Nascimento LS1, E Silva AC3.

Author information: 1 Federal University of Ceará, Community Health Department, Fortaleza, Ceará, BR. 2 Federal University of Rio de Janeiro, Rio de Janeiro, BR. 3 Christus University Center (Unichristus), Fortaleza, Ceará, BR.

 

Abstract

BACKGROUND:

Brazil presented an alarming number of newborns with microcephaly in the years 2015 and 2016. The investigation of the cases raised the suspicion of the association of these cases with maternal infections by the zika virus. Also, in 2015, there was an epidemic of zika virus infection in Brazil, reinforcing this hypothesis.

OBJECTIVE:

The objective of this study was to identify factors associated with the diagnosis of microcephaly in newborns, including zika virus infection.

METHODS:

We conducted a case-control study. The cases were defined as children who received clinical and imaging diagnosis of microcephaly, born after October 2015 in Ceará, Brazil, which recorded the highest number of microcephaly cases in Brazil during the outbreak. The cases were identified in medical records of public and private maternity hospitals and in child development stimulation clinics tracked until June 2017. Epidemiological, clinical, and socioeconomic variables were collected, visiting their homes and confirming data from their medical records. Controls were children without microcephaly identified in the vicinity of the residence of each case. Logistic regression models were used to control confounding.

FINDINGS:

We evaluated 58 cases and 116 controls. The odds of having a baby with microcephaly was 14 times higher among mothers who had zika virus infection (p < 0.001), after multivariate analysis. Arboviruses infections symptoms, as fever (p = 0.220), skin change (p < 0.001), and joint pain (p = 0.002) also demonstrated an association with microcephaly.

CONCLUSIONS:

Maternal infection zika virus was associated with a diagnosis of microcephaly. Our study contributes to the investigation of the epidemiological factors associated with the diagnosis of microcephaly.

© 2019 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0/.

PMID: 31468955 DOI: 10.5334/aogh.2394

Keywords: Zika Virus; Zika Congenital Syndrome; Microcephaly; Brazil.

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Insights into the #ZIKV NS1 #Virology from Different #Strains through a Fine Analysis of #Physicochemical Properties (ACS Omega, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

ACS Omega. 2018 Nov 29;3(11):16212-16229. doi: 10.1021/acsomega.8b02081. eCollection 2018 Nov 30.

Insights into the ZIKV NS1 Virology from Different Strains through a Fine Analysis of Physicochemical Properties.

Poveda-Cuevas SA1,2,3, Etchebest C4,5,6,3, Barroso da Silva FL1,2,3,7.

Author information: 1 Programa Interunidades em Bioinformática, Universidade de São Paulo, São Paulo 05508-090, Brazil. 2 Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo 14040-903, Brazil. 3 University of São Paulo and Université Sorbonne Paris Cité Joint International Laboratory in Structural Bioinformatics. 4 Institut National de la Transfusion Sanguine, Paris 75015, France. 5 Biologie Intégrée du Globule Rouge, Equipe 2, Dynamique des Structures et des Interactions Moléculaires, Institut National de la Santé et de la Recherche Médicale, UMR_S 1134, Paris 75015, France. 6 Université Sorbonne Paris Cité and Université Paris Diderot, 75013 Paris, France. 7 Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina 27606, United States.

 

Abstract

The flavivirus genus has several organisms responsible for generating various diseases in humans. Recently, especially in tropical regions, Zika virus (ZIKV) has raised great health concerns due to the high number of cases affecting the area during the last years that has been accompanied by a rise in the cases of the Guillain-Barré syndrome and fetal and neonatal microcephaly. Diagnosis is still difficult since the clinical symptoms between ZIKV and other flaviviruses (e.g., dengue and yellow fever) are highly similar. The understanding of their common physicochemical properties that are pH-dependent and biomolecular interaction features and their differences sheds light on the relation strain-virulence and might suggest alternative strategies toward differential serological diagnostics and therapeutic intervention. Due to their immunogenicity, the primary focus of this study was on the ZIKV nonstructural proteins 1 (NS1). By means of computational studies and semiquantitative theoretical analyses, we calculated the main physicochemical properties of this protein from different strains that are directly responsible for the biomolecular interactions and, therefore, can be related to the differential infectivity of the strains. We also mapped the electrostatic differences at both the sequence and structural levels for the strains from Uganda to Brazil, which could suggest possible molecular mechanisms for the increase of the virulence of ZIKV in Brazil. Exploring the interfaces used by NS1 to self-associate in some different oligomeric states and interact with membranes and the antibody, we could map the strategy used by the ZIKV during its evolutionary process. This indicates possible molecular mechanisms that can be correlated with the different immunological responses. By comparing with the known antibody structure available for the West Nile virus, we demonstrated that this antibody would have difficulties to neutralize the NS1 from the Brazilian strain. The present study also opens up perspectives to computationally design high-specificity antibodies.

PMID: 31458257 PMCID: PMC6643396 DOI: 10.1021/acsomega.8b02081

Keywords: Flavivirus; Zika Virus; Brazil.

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Early Gross #Motor #Development Among Brazilian #Children with #Microcephaly Born Right After #Zika Virus #Infection #Outbreak (J Dev Behav Pediatr., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Dev Behav Pediatr. 2019 Aug 22. doi: 10.1097/DBP.0000000000000722. [Epub ahead of print]

Early Gross Motor Development Among Brazilian Children with Microcephaly Born Right After Zika Virus Infection Outbreak.

A Ventura P1,2, C Lage ML1, L de Carvalho A2, S Fernandes A2, B Taguchi T2, Nascimento-Carvalho CM1,3.

Author information: 1 Post-graduation Program in Health Sciences, Federal University of Bahia School of Medicine, Salvador, Brazil. 2 SARAH Network of Rehabilitation Hospital, Salvador, Brazil. 3 Department of Paediatrics, Federal University of Bahia School of Medicine, Salvador, Brazil.

 

Abstract

OBJECTIVE:

To assess the gross motor development of children with presumed congenital Zika virus (ZIKV) infection over the first 2 years of their lives.

METHODS:

Seventy-seven children were assessed at the median ages of 11, 18, and 24 months, using the evaluative instrument Gross Motor Function Measure (GMFM-66). At the third assessment, the children with diagnoses of cerebral palsy (CP) were classified by severity through the Gross Motor Function Classification System (GMFCS) and stratified by topography indicating the predominantly affected limbs. With these instruments in combination and using the motor development curves as reference, the rate of development and functional ability were estimated.

RESULTS:

At 2 years of age, all children had the diagnosis of CP. Seventy-four (96.1%) presented gross motor skills similar to those of children aged 4 months or younger, according to the World Health Organization’s standard. The GMFM-66 median score among the 73 (94.8%) children with quadriplegia and GMFCS level V showed significant change between 11 and 18 months (p < 0.001) and between 11 and 24 months (p < 0.001). No significant difference (p = 0.076) was found between 18 and 24 months.

CONCLUSION:

Despite showing some gross motor progress during the initial 18 months of life, these children with presumed congenital ZIKV infection and CP experienced severe motor impairment by 2 years of age. According to the motor development curves, these children with quadriplegia have probably already reached about 90% of their motor development potential.

PMID: 31453893 DOI: 10.1097/DBP.0000000000000722

Keywords: Zika Virus; Zika Congenital Syndrome; Neurology; Pediatrics; Brazil.

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#Epidemiological profile of #Zika, #Dengue and #Chikungunya virus #infections identified by medical and molecular evaluations in #Rondonia, #Brazil (Rev Inst Med Trop Sao Paulo, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Rev Inst Med Trop Sao Paulo. 2019 Aug 19;61:e40. doi: 10.1590/S1678-9946201961040.

Epidemiological profile of Zika, Dengue and Chikungunya virus infections identified by medical and molecular evaluations in Rondonia, Brazil.

Vieira DS1,2,3, Zambenedetti MR4, Requião L4, Borghetti IA4,5, Luna LKS4, Santos AOD1,3, Taborda RLM3, Pereira DB3, Krieger MA4,6, Salcedo JMV1,3, Rampazzo RCP4.

Author information: 1 Fundação Oswaldo Cruz Rondônia, Porto Velho, Rondônia, Brazil. 2 Universidade Federal de Rondônia, Programa de Pós-Graduação em Biologia Experimental, Porto Velho, Rondônia, Brazil. 3 Centro de Pesquisa em Medicina Tropical, Porto Velho, Rondônia, Brazil. 4 Instituto de Biologia Molecular do Paraná, Curitiba, Paraná, Brazil. 5 Universidade Federal do Paraná, Departamento de Engenharia de Bioprocessos e Biotecnologia, Curitiba, Paraná, Brazil. 6 Instituto Carlos Chagas, Curitiba, Paraná, Brazil.

 

Abstract

Several arboviruses have emerged and/or re-emerged in North, Central and South-American countries. Viruses from some regions of Africa and Asia, such as the Zika and Chikungunya virus have been introduced in new continents causing major public health problems. The aim of this study was to investigate the presence of RNA from Zika, Dengue and Chikungunya viruses in symptomatic patients from Rondonia, where the epidemiological profile is still little known, by one-step real-time RT-PCR. The main clinical signs and symtoms were fever (51.2%), headache (78%), chills (6.1%), pruritus (12.2%), exanthema (20.1%), arthralgia (35.3%), myalgia (26.8%) and retro-orbital pain (19.5%). Serum from 164 symptomatic patients were collected and tested for RNA of Zika, Dengue types 1 to 4 and Chikungunya viruses, in addition to antibodies against Dengue NS1 antigen. Direct microscopy for Malaria was also performed. Only ZIKV RNA was detected in 4.3% of the patients, and in the remaining 95.7% of the patients RNA for Zika, Dengue and Chikungunya viruses were not detected. This finding is intriguing as the region has been endemic for Dengue for a long time and more recently for Chikungunya virus as well. The results indicated that medical and molecular parameters obtained were suitable to describe the first report of symptomatic Zika infections in this region. Furthermore, the low rate of detection, compared to clinical signs and symptoms as the solely diagnosis criteria, suggests that molecular assays for detection of viruses or other pathogens that cause similar symptoms should be used and the corresponding diseases could be included in the compulsory notification list.

PMID: 31432989 DOI: 10.1590/S1678-9946201961040

Keywords: Zika Virus; Dengue fever; Chikungunya fever; Seroprevalence; Brazil.

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#Genetic and biological characterisation of #Zika virus isolates from different #Brazilian #regions (Mem Inst Oswaldo Cruz, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Mem Inst Oswaldo Cruz. 2019;114:e190150. doi: 10.1590/0074-02760190150. Epub 2019 Aug 19.

Genetic and biological characterisation of Zika virus isolates from different Brazilian regions.

Strottmann DM1, Zanluca C1, Mosimann ALP1, Koishi AC1, Auwerter NC1, Faoro H2, Cataneo AHD1, Kuczera D1, Wowk PF1, Bordignon J1, Duarte Dos Santos CN1.

Author information: 1 Fundação Oswaldo Cruz-Fiocruz, Instituto Carlos Chagas, Laboratório de Virologia Molecular, Curitiba, PR, Brasil. 2 Fundação Oswaldo Cruz-Fiocruz, Instituto Carlos Chagas, Laboratório de Regulação da Expressão Gênica, Curitiba, PR, Brasil.

 

Abstract

BACKGROUND:

Zika virus (ZIKV) infections reported in recent epidemics have been linked to clinical complications that had never been associated with ZIKV before. Adaptive mutations could have contributed to the successful emergence of ZIKV as a global health threat to a nonimmune population. However, the causal relationships between the ZIKV genetic determinants, the pathogenesis and the rapid spread in Latin America and in the Caribbean remain widely unknown.

OBJECTIVES:

The aim of this study was to characterise three ZIKV isolates obtained from patient samples during the 2015/2016 Brazilian epidemics.

METHODS:

The ZIKV genomes of these strains were completely sequenced and in vitro infection kinetics experiments were carried out in cell lines and human primary cells.

FINDINGS:

Eight nonsynonymous substitutions throughout the viral genome of the three Brazilian isolates were identified. Infection kinetics experiments were carried out with mammalian cell lines A549, Huh7.5, Vero E6 and human monocyte-derived dendritic cells (mdDCs) and insect cells (Aag2, C6/36 and AP61) and suggest that some of these mutations might be associated with distinct viral fitness. The clinical isolates also presented differences in their infectivity rates when compared to the well-established ZIKV strains (MR766 and PE243), especially in their abilities to infect mammalian cells.

MAIN CONCLUSIONS:

Genomic analysis of three recent ZIKV isolates revealed some nonsynonymous substitutions, which could have an impact on the viral fitness in mammalian and insect cells.

PMID: 31432892 DOI: 10.1590/0074-02760190150

Keywords: Zika Virus; Brazil.

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