The Transcriptional and Protein Profile From #Human Infected #Neuroprogenitor Cells Is Strongly Correlated to #Zika Virus #Microcephaly #Cytokines Phenotype Evidencing a Persistent Inflammation in the #CNS (Front Immunol., abstract)

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

Front Immunol. 2019 Aug 16;10:1928. doi: 10.3389/fimmu.2019.01928. eCollection 2019.

The Transcriptional and Protein Profile From Human Infected Neuroprogenitor Cells Is Strongly Correlated to Zika Virus Microcephaly Cytokines Phenotype Evidencing a Persistent Inflammation in the CNS.

Lima MC1, de Mendonça LR1, Rezende AM1, Carrera RM2, Aníbal-Silva CE1, Demers M3, D’Aiuto L3, Wood J3, Chowdari KV3, Griffiths M2, Lucena-Araujo AR4, Barral-Netto M5, Azevedo EAN1, Alves RW1, Farias PCS1, Marques ETA1,6, Castanha PMS6, Donald CL7, Kohl A7, Nimgaonkar VL3,8, Franca RFO1.

Author information: 1 Oswaldo Cruz Foundation/Fiocruz, Institute Aggeu Magalhães, Recife, Brazil. 2 Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom. 3 Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States. 4 Federal University of Pernambuco/UFPE, Recife, Brazil. 5 Oswaldo Cruz Foundation/Fiocruz, Institute Gonçalo Moniz, Salvador, Brazil. 6 Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, United States. 7 MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom. 8 Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States.



Zika virus (ZIKV) infection during pregnancy is associated with microcephaly, a congenital malformation resulting from neuroinflammation and direct effects of virus replication on the developing central nervous system (CNS). However, the exact changes in the affected CNS remain unknown. Here, we show by transcriptome analysis (at 48 h post-infection) and multiplex immune profiling that human induced-neuroprogenitor stem cells (hiNPCs) respond to ZIKV infection with a strong induction of type-I interferons (IFNs) and several type-I IFNs stimulated genes (ISGs), notably cytokines and the pro-apoptotic chemokines CXCL9 and CXCL10. By comparing the inflammatory profile induced by a ZIKV Brazilian strain with an ancestral strain isolated from Cambodia in 2010, we observed that the response magnitude differs among them. Compared to ZIKV/Cambodia, the experimental infection of hiNPCs with ZIKV/Brazil resulted in a diminished induction of ISGs and lower induction of several cytokines (IFN-α, IL-1α/β, IL-6, IL-8, and IL-15), consequently favoring virus replication. From ZIKV-confirmed infant microcephaly cases, we detected a similar profile characterized by the presence of IFN-α, CXCL10, and CXCL9 in cerebrospinal fluid (CSF) samples collected after birth, evidencing a sustained CNS inflammation. Altogether, our data suggest that the CNS may be directly affected due to an unbalanced and chronic local inflammatory response, elicited by ZIKV infection, which contributes to damage to the fetal brain.

KEYWORDS: Zika congenital syndrome and cytokines; Zika virus; central nervous system; inflammation; interferonopathy; microcephaly; type-I interferon

PMID: 31474994 PMCID: PMC6707094 DOI: 10.3389/fimmu.2019.01928

Keywords: Zika Virus; Microcephaly; Zika Congenital Syndrome.



#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.




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.


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


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.


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.


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

PMID: 31468955 DOI: 10.5334/aogh.2394

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


#Host and viral #mechanisms of #congenital #Zika #syndrome (Virulence, abstract)

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

Virulence. 2019 Dec;10(1):768-775. doi: 10.1080/21505594.2019.1656503.

Host and viral mechanisms of congenital Zika syndrome.

Liang B1, Guida JP2, Costa Do Nascimento ML2, Mysorekar IU1,3,4.

Author information: 1 Department of Obstetrics and Gynecology, Washington University School of Medicine , St. Louis , MO , USA. 2 Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas , Campinas , Brazil. 3 Department of Pathology and Immunology, Washington University School of Medicine , St. Louis , MO , USA. 4 Center for Reproductive Health Sciences, Washington University School of Medicine , St. Louis , MO , USA.



In 2015-2016, in the Americas, and especially in northeast Brazil, a significant number of cases of microcephaly and other congenital brain abnormalities were linked with an outbreak of Zika virus (ZIKV) infection in pregnant women. While maternal symptoms of ZIKV are generally mild and self-limiting, clinical presentation in fetuses and newborns infected is extensive and includes microcephaly, decreased cortical development, atrophy and hypoplasia of the cerebellum and cerebellar vermis, arthrogryposis, and polyhydramnios. The term congenital ZIKV syndrome (CZS) was introduced to describe the range of findings associated with maternal-fetal ZIKV transmission. ZIKV is primarily transmitted by Aedes aegypti mosquitoes, however non-vector-dependent routes are also possible. Mechanisms of maternal-fetal transmission remain unknown, and the trans-placental route has been extensively studied in animal models and in human samples. The aim of this review was to summarize recent studies that helped to elucidate the mechanism of CZS in animal models and observational studies. There are still challenges in the diagnosis and prevention of CZS in humans, due to the large gap that remains in translating ZIKV research to clinical practice. Translational research linking governments, local health workers, scientists and industry is fundamental to improve care for mothers and children.

KEYWORDS: Placenta; autophagy; hydroxychloroquine; interferon lambda; trophoblast; type I interferon

PMID: 31451049 DOI: 10.1080/21505594.2019.1656503

Keywords: Zika Virus; Zika Congenital Syndrome; Pregnancy.


#Risk of #Zika #microcephaly correlates with features of #maternal #antibodies (J Exp Med., abstract)

[Source: Journal of Experimental Medicine, full page: (LINK). Abstract, edited.]

Risk of Zika microcephaly correlates with features of maternal antibodies

Davide F. Robbiani, Priscilla C. Olsen, Federico Costa,Qiao Wang, Thiago Y. Oliveira, Nivison Nery, Adeolu Aromolaran, Mateus S. do Rosário, Gielson A. Sacramento, Jaqueline S. Cruz, Ricardo Khouri, Elsio A. Wunder, Adriana Mattos, Bruno de Paula Freitas, Manoel Sarno, Gracinda Archanjo, Dina Daltro, Gustavo B.S. Carvalho, Kleber Pimentel, Isadora C. de Siqueira, João R.M. de Almeida, Daniele F. Henriques, Juliana A. Lima, Pedro F.C. Vasconcelos, Dennis Schaefer-Babajew, Stephanie A. Azzopardi, Leonia Bozzacco, Anna Gazumyan, Rubens Belfort, Ana P. Alcântara, Gustavo Carvalho, Licia Moreira, Katiaci Araujo, Mitermayer G. Reis, Rebekah I. Keesler, Lark L. Coffey, Jennifer Tisoncik-Go, Michael Gale, Lakshmi Rajagopal, Kristina M. Adams Waldorf, Dawn M. Dudley, Heather A. Simmons, Andres Mejia, David H. O’Connor, Rosemary J. Steinbach, Nicole Haese, Jessica Smith, Anne Lewis, Lois Colgin, Victoria Roberts, Antonio Frias, Meredith Kelleher, Alec Hirsch, Daniel N. Streblow, Charles M. Rice, Margaret R. MacDonald, Antonio R.P. de Almeida, Koen K.A. Van Rompay, Albert I. Ko, Michel C. Nussenzweig

DOI: 10.1084/jem.20191061 | Published August 14, 2019



Zika virus (ZIKV) infection during pregnancy causes congenital abnormalities, including microcephaly. However, rates vary widely, and the contributing risk factors remain unclear. We examined the serum antibody response to ZIKV and other flaviviruses in Brazilian women giving birth during the 2015–2016 outbreak. Infected pregnancies with intermediate or higher ZIKV antibody enhancement titers were at increased risk to give birth to microcephalic infants compared with those with lower titers (P < 0.0001). Similarly, analysis of ZIKV-infected pregnant macaques revealed that fetal brain damage was more frequent in mothers with higher enhancement titers. Thus, features of the maternal antibodies are associated with and may contribute to the genesis of ZIKV-associated microcephaly.

Keywords: Zika virus; Pregnancy; Immunopathology; Microcephaly.


#Association between #Zika virus #microcephaly in the #newborn with the rs3775291 variant in Toll-Like receptor 3 and rs1799964 variant at TNFα gene (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Association between Zika virus microcephaly in the newborn with the rs3775291 variant in Toll-Like receptor 3 and rs1799964 variant at TNFα gene

Camilla N O Santos, Danielle R Ribeiro, Juliana A Cardoso, Rodrigo A Cazzaniga, Lucas S Magalhães, Mércia S F de Souza, Adriana B L Fonseca, Ana J B Bispo,Roseane L S Porto, Cliomar Alves dos Santos, Ângela M da Silva, Mauro M Teixeira, Roque P de Almeida, Amélia R de Jesus

The Journal of Infectious Diseases, jiz392,

Published: 28 July 2019



Congenital Zika syndrome (CZS) is a cluster of malformation and the mechanisms that lead it are still unclear. Using hypothesis-driven candidate genes and their function in viral infections, Single Nucleotide Polymorphisms (SNP) were genotyped by qPCR in a sample population from Sergipe State, Brazil. This study shows that rs3775291 SNP at TLR3, that trigger to type I interferons antiviral responses, in mothers infected by Zika during pregnancy is associated with CZS occurrence (OR2.19, 95% CI1.158 – 4.148). Moreover, the rs1799964 SNP at TNFα gene in the CZS babies is associated with severe microcephaly (OR2.63, 95% CI 1.13 – 6.21).

Congenital Zika Syndrome, Microcephaly, Polymorphism, TLR3, TNFα

This content is only available as a PDF.


Author notes

These authors contributed equally to this article.

Scientists sponsored by CNPq.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail:

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (

Keywords: Zika Virus; Zika Congenital Syndrome; Pregnancy; Microcephaly; Genetics.


Descriptive study of suspected #congenital #Zika #syndrome cases during the 2015-2016 #epidemic in #Brazil (Rev Soc Bras Med Trop., abstract)

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

Rev Soc Bras Med Trop. 2019 Jul 18;52:e20190105. doi: 10.1590/0037-8682-0105-2019.

Descriptive study of suspected congenital Zika syndrome cases during the 2015-2016 epidemic in Brazil.

Roma JHF1,2, Alves RC1, Silva VSD1, Ferreira MJ1, Araújo C1, Pavoni JHC1.

Author information: 1 Curso de Graduação em Medicina, Instituto de Ciências Exatas e Naturais, Universidade Federal de Mato Grosso, Rondonópolis, MT, Brasil. 2 Programa de Pós-graduação em Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.




Clinical and epidemiological data on suspected congenital Zika syndrome (CZS) cases from southern Mato Grosso (MT) in Brazil during the Zika virus (ZIKV) outbreak in 2015-2016 were evaluated.


This is a descriptive case series study of newborns whose mothers were suspected cases of ZIKV infections during their pregnancies. The medical records of all the suspected CZS cases (mothers and newborns) treated by the specialized ambulatory service from June 2015 to August 2016 were analyzed.


Twenty suspected CZS cases were included in these analyses. They were categorized into four groups based on the clinical and laboratory findings: confirmed cases (n=1), highly probable cases (n=13), moderately probable cases (n=5), and somewhat probable cases (n=1). The mothers tested negative for STORCH (syphilis, toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex) and other important congenital infections; however, specific ZIKV tests were not performed during the study period. Microcephaly was observed in the majority of these newborns, and all the patients showed altered cranial computed tomography image findings. Extracranial abnormalities such as arthrogryposis, and otological and ophthalmological manifestations were also observed.


Although ZIKV was not confirmed to cause the congenital malformations, this study demonstrated that the clinical and epidemiological findings associated with a STORCH exclusion strengthened the CZS diagnosis. The suspected cases in MT occurred simultaneously with the first CZS cases reported in Brazil, suggesting ZIKV circulation in the study region during the same period.

PMID: 31340371 DOI: 10.1590/0037-8682-0105-2019

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


Underreporting of #Fatal #Congenital #Zika #Syndrome, #Mexico, 2016–2017 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 8—August 2019 / Dispatch

Underreporting of Fatal Congenital Zika Syndrome, Mexico, 2016–2017

Victor M. Cardenas  , Angel Jose Paternina-Caicedo, and Ernesto Benito Salvatierra

Author affiliations: University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA (V.M. Cardenas); Universidad Nacional de Colombia, Bogota, Colombia (A.J. Paternina-Caicedo); Unidad San Cristóbal, Chiapas, Mexico (E.B. Salvatierra)



To determine completeness of fatal congenital Zika syndrome reporting in Mexico, we examined data from the Mexican National Institute of Statistics and Geography. We found that an estimated 50% more infants died from microcephaly attributable to congenital Zika syndrome during 2016–2017 than were reported by the existing surveillance system.

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