Biology subjects

Jeronimo, S. M. B.

Publications and source records attributed to Jeronimo, S. M. B..

3 recordsLinked to original sources

bioRxiv2025

Maturation of the glymphatic system confers innate resistance of the brain to Zika virus infection

The maturation of the glymphatic system initiates fluid dynamics in the central nervous system (CNS). Here, we demonstrate that the initiating glymphatic function results in a steep reduction in the susceptibility of the CNS to Zika virus (ZIKV) infection. In mice, ZIKV injection before glymphatic system maturation leads to widespread infection, vascular deformation, and disruption of Aqp4+ astrocytic networks. After the glymphatic system formation, the same challenge fails to cause disease or persistent infection. Pharmacological inhibition of vasopressin receptor 1a, which reduces perivascular fluid dynamics, reopens the window of susceptibility to ZIKV-related disease. These findings reveal the glymphatic system as an innate protective barrier that limits viral spread in the brain parenchyma and suggest a possible explanation for why late-gestation human fetuses and newborns are less susceptible to ZIKV. Moreover, these data indicate that children with ZIKV-caused malformations can have continuous brain inflammation due to a defective glymphatic system.

neuroscience↗

bioRxiv2023

A novel approach to identify cross-identity peptides between Epstein-Barr virus and central nervous system proteins in Guillain-Barre syndrome and multiple sclerosis

BackgroundGuillain-Barre Syndrome (GBS) and multiple sclerosis are autoimmune diseases associated with an immune system attack response against peripheral and central nervous system autoantigens, respectively. Given the potential of Epstein-Barr virus (EBV) as a risk factor for both multiple sclerosis and GBS, the present study aimed to identify crucial residues among potential EBV CD4+ T lymphocyte epitopes and nervous system proteins. MethodsPublic databases (Allele Frequency Net Database, Immune Epitope Database, Genevestigator and Protein Atlas) were used to select proteins abundant in the nervous system, EBV immunogenic proteins, and HLA haplotypes. Computational tools were employed for predicting HLA-binding peptides and immunogenicity. For this, we developed immuno-cross, a Python tool (https://github.com/evoMOL-Lab/immuno-cross) to compare residue identity among nonamers. ResultsWe found ten proteins from the nervous system and 28 from EBV, which were used for predicting the binding peptides of 21 common HLAs in the world population. A total of 1411 haplotypes were distributed among 51 pairs of HLAs. Simulations were performed to determine whether nonamers from the EBV and nervous system proteins targeted TCR-contact residues. Then, three selection criteria were used, based on the relevance of each contact in the TCR-peptide-MHC interaction. The primary contact has to be located at position P5, and the positions P2, P3, and P8 were weighed as secondary, and P4, P6, and P7 were considered tertiary. Nonamers of EBV proteins and myelin proteins were combined in pairs and compared based on predefined selection criteria. The Periaxin protein had the highest number of nonamers pairs among PNS proteins, with 35 pairs. Four nonamers pairs from APLP1, two from CNP, and two from MBP bind to alleles of the haplotype DR-15. ConclusionsThe new approach proposed herein revealed that peptides derived from nervous system and EBV proteins share identical residues at critical contact points, which supports molecular mimicry. These findings suggest cross-reactivity between them and that the nonamer pairs identified with this approach have the potential to be an autoantigen. Experimental studies are needed to validate these findings.

bioinformatics↗

bioRxiv2019

Novel Variants in COL4A3 and COL4A4 are Causes of Alport Syndrome in Rio Grande do Norte, Brazil

BackgroundAlport syndrome is a progressive and hereditary nephropathy, characterized by hematuria and proteinuria, and extrarenal manifestations as hearing loss and eye abnormalities. The disease can be expressed as autosomal recessive or dominant, caused by variants in COL4A3 and COL4A4 loci, respectively, or X-linked caused by variants in COL4A5 locus. MethodsTwo unrelated families with Alport Syndrome from northeast of Brazil were studied and whole exome sequencing were performed. DNA sequences were mapped against the human genome (GRCh38/hg38 build) to identify associated mutations. ResultsVariant analysis showed deleterious variants in COL4A3 and COL4A4 loci in chromosome 2. Two variants were detected with alternative alleles in a homozygous state in the probands. One novel premature stop codon at position 481 of COL4A3 protein is present in one family and one frameshift mutation leading to a premature stop codon at position 786 of COL4A4 protein in the other family. Both Alport cases presented their variants surrounded by a broad runs of homozygosity (ROH). ConclusionsThe autosome recessive inheritance coupled with the runs of homozygosity in both families suggest inbreeding.

genomics↗