Association Between Zika Virus Microcephaly in Newborns With the rs3775291 Variant in Toll-Like Receptor 3 and rs1799964 Variant at Tumor Necrosis Factor-α Gene

Santos, Camilla Natália Oliveira; Ribeiro, Danielle Rodrigues; Alves, Juliana Cardoso; Cazzaniga, Rodrigo Anselmo; Magalhães, Lucas Sousa; Souza, Mércia Simone Feitosa de; Fonseca, Adriana B L; Bispo, Ana Jovina Barreto; Porto, Roseane Lima Santos; Santos, Cliomar Alves dos; Silva, Ângela M. Da; Teixeira, Mauro Martins; Almeida, Roque Pacheco de; Jesus, Amélia Ribeiro de

doi:10.1093/infdis/jiz392

Cited by 31 publications

(42 citation statements)

References 12 publications

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“…Mild or moderate microcephaly was defined if the head circumference was between 2 and 3 standard deviation (SD) below the mean for sex and age, and severe if it was 3 or more SD below the mean [19]. Children with 2SD of microcephaly were compared to children with 3SD of microcephaly for the frequency of two variables already reported in the literature as related to these phenotypes-trimester of ZIKV infection and TNF gene [20,21]. The results of such analysis are presented in Table 5.…”

Section: Genetic Susceptibility To Czs and Severe Microcephalymentioning

confidence: 99%

Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly

Gomes

Sgarioni

Boquett

et al. 2021

Viruses

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Zika virus (ZIKV) causes Congenital Zika Syndrome (CZS) in individuals exposed prenatally. Here, we investigated polymorphisms in VEGFA, PTGS2, NOS3, TNF, and NOS2 genes as risk factors to CZS. Forty children with CZS and forty-eight children who were in utero exposed to ZIKV infection, but born without congenital anomalies, were evaluated. Children with CZS were predominantly infected by ZIKV in the first trimester (p < 0.001) and had mothers with lower educational level (p < 0.001) and family income (p < 0.001). We found higher risk of CZS due the allele rs2297518[A] of NOS2 (OR = 2.28, CI 95% 1.17–4.50, p = 0.015). T allele and TT/CT genotypes of the TNF rs1799724 and haplotypes associated with higher expression of TNF were more prevalent in children with CZS and severe microcephaly (p = 0.029, p = 0.041 and p = 0.030, respectively). Our findings showed higher risk of CZS due ZIKV infection in the first trimester and suggested that polymorphisms in NOS2 and TNF genes affect the risk of CZS and severe microcephaly.

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Section: Genetic Susceptibility To Czs and Severe Microcephalymentioning

confidence: 99%

Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly

Gomes

Sgarioni

Boquett

et al. 2021

Viruses

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Section: The Advent Of Induced Pluripotent Stem Cells and The Associamentioning

confidence: 96%

“…A case-control study of a Brazilian cohort identified a statistically significant association of maternal adenylate cyclase genes with the development of CZS [85]. Comparable to the identification of the TLR2 2258 G>A SNP, the T allele in SNP rs3775291 of the TLR3 gene is associated with a risk of CZS [86]. Furthermore, a link between the T allele in SNP rs1799964 at tumor necrosis factor α and the severity of ZIKV-induced microcephaly was identified [86].…”

Section: The Advent Of Induced Pluripotent Stem Cells and The Associamentioning

confidence: 99%

“…Comparable to the identification of the TLR2 2258 G>A SNP, the T allele in SNP rs3775291 of the TLR3 gene is associated with a risk of CZS [86]. Furthermore, a link between the T allele in SNP rs1799964 at tumor necrosis factor α and the severity of ZIKV-induced microcephaly was identified [86]. The potential these case-control studies hold for hiPSC-based models was revealed by the analysis of possible host genetic variants in NPCs derived from hiPSC generated from erythroblasts from a healthy control group and from the following pairs of Brazilian twins that were exposed to ZIKV during pregnancy: monozygotic twins Figure 1A.…”

Section: The Advent Of Induced Pluripotent Stem Cells and The Associamentioning

confidence: 99%

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Pluripotent Stem Cell-Based Models: A Peephole into Virus Infections during Early Pregnancy

Claus

Jung

Hübschen

2020

Cells

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The rubella virus (RV) was the first virus shown to be teratogenic in humans. The wealth of data on the clinical symptoms associated with congenital rubella syndrome is in stark contrast to an incomplete understanding of the forces leading to the teratogenic alterations in humans. This applies not only to RV, but also to congenital viral infections in general and includes (1) the mode of vertical transmission, even at early gestation, (2) the possible involvement of inflammation as a consequence of an activated innate immune response, and (3) the underlying molecular and cellular alterations. With the progress made in the development of pluripotent stem cell-based models including organoids and embryoids, it is now possible to assess congenital virus infections on a mechanistic level. Moreover, antiviral treatment options can be validated, and newly emerging viruses with a potential impact on human embryonal development, such as that recently reflected by the Zika virus (ZIKV), can be characterized. Here, we discuss human cytomegalovirus (HCMV) and ZIKV in comparison to RV as viruses with well-known congenital pathologies and highlight their analysis on current models for the early phase of human development. This includes the implications of their genetic variability and, as such, virus strain-specific properties for their use as archetype models for congenital virus infections. In this review, we will discuss the use of induced pluripotent stem cells (iPSC) and derived organoid systems for the study of congenital virus infections with a focus on their prominent aetiologies, HCMV, ZIKV, and RV. Their assessment on these models will provide valuable information on how human development is impaired by virus infections; it will also add new insights into the normal progression of human development through the analysis of developmental pathways in the context of virus-induced alterations. These are exciting perspectives for both developmental biology and congenital virology.

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“…The human subpopulations most vulnerable to influenza virus infections are children, pregnant women, and persons over 65 years old. [77,190,[193][194][195][196] Human (in vivo) Pathogenic Higher levels of IFN-β in severe vs. nonsevere dengue children [197] Human (in vivo) Pathogenic Higher levels of IFN-β in primary DHF patients compared to those with primary DF [198] ZIKV Human (in vivo) Protective SNP at TLR-3 that decreased IFN-I response has been associated with microcephaly in newborns [232] Human (in vitro) Protective [45][46][47]. Once activated, RIG-I and MDA5 interact with the mitochondrial antiviral-signaling protein (MAVS), leading the activation of NF-κB and IRF-3 to stimulate IFN production (Figure 2).…”

Section: Human Ifn-i Responses To Viral Pathogensmentioning

confidence: 99%

Human Type I Interferon Antiviral Effects in Respiratory and Reemerging Viral Infections

Acosta

Byrne

Hijano

et al. 2020

Journal of Immunology Research

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Type I interferons (IFN-I) are a group of related proteins that help regulate the activity of the immune system and play a key role in host defense against viral infections. Upon infection, the IFN-I are rapidly secreted and induce a wide range of effects that not only act upon innate immune cells but also modulate the adaptive immune system. While IFN-I and many IFN stimulated genes are well-known for their protective antiviral role, recent studies have associated them with potential pathogenic functions. In this review, we summarize the current knowledge regarding the complex effects of human IFN-I responses in respiratory as well as reemerging flavivirus infections of public health significance and the molecular mechanisms by which viral proteins antagonize the establishment of an antiviral host defense. Antiviral effects and immune modulation of IFN-stimulated genes is discussed in resisting and controlling pathogens. Understanding the mechanisms of these processes will be crucial in determining how viral replication can be effectively controlled and in developing safe and effective vaccines and novel therapeutic strategies.

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Association Between Zika Virus Microcephaly in Newborns With the rs3775291 Variant in Toll-Like Receptor 3 and rs1799964 Variant at Tumor Necrosis Factor-α Gene

Cited by 31 publications

References 12 publications

Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly

Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly

Pluripotent Stem Cell-Based Models: A Peephole into Virus Infections during Early Pregnancy

Human Type I Interferon Antiviral Effects in Respiratory and Reemerging Viral Infections

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