Dataset Information

In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus.

ABSTRACT: Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.

SUBMITTER: Azevedo RSS

PROVIDER: S-EPMC5758755 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus.

Azevedo Raimunda S S RSS de Sousa Jorge R JR Araujo Marialva T F MTF Martins Filho Arnaldo J AJ de Alcantara Bianca N BN Araujo Fernanda M C FMC Queiroz Maria G L MGL Cruz Ana C R ACR Vasconcelos Beatriz H Baldez BHB Chiang Jannifer O JO Martins Lívia C LC Casseb Livia M N LMN da Silva Eliana V EV Carvalho Valéria L VL Vasconcelos Barbara C Baldez BCB Rodrigues Sueli G SG Oliveira Consuelo S CS Quaresma Juarez A S JAS Vasconcelos Pedro F C PFC

Scientific reports 20180108 1

Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with ...[more]

PMID: 29311619

Similar Datasets

Project description:BACKGROUND:Zika virus (ZIKV) is an emerging human pathogen. Since its arrival in the Western hemisphere, from Africa via Asia, it has become a serious threat to pregnant women, causing microcephaly and other neuropathies in developing fetuses. The mechanisms behind these teratogenic effects are unknown, although epidemiological evidence suggests that microcephaly is not associated with the original, African lineage of ZIKV. The sequences of 196 published ZIKV genomes were used to assess whether recently proposed mechanistic explanations for microcephaly are supported by molecular level changes that may have increased its virulence since the virus left Africa. For this we performed phylogenetic, recombination, adaptive evolution and tetramer frequency analyses, and compared protein sequences for the presence of protease cleavage sites, Pfam domains, glycosylation sites, signal peptides, trans-membrane protein domains, and phosphorylation sites. RESULTS:Recombination events within or between Asian and Brazilian lineages were not observed, and likewise there were no differences in protease cleavage, glycosylation sites, signal peptides or trans-membrane domains between African and Brazilian strains. The frequency of Retinoic Acid Response Element (RARE) sequences was increased in Brazilian strains. Genetic adaptation was also apparent by tetramer signatures that had undergone major changes in the past but has stabilized in the Brazilian lineage despite subsequent geographic spread, suggesting the viral population presently propagates in the same host species in various regions. Evidence for selection pressure was recognized for several amino acid sites in the Brazilian lineage compared to the African lineage, mainly in nonstructural proteins, especially protein NS4B. A number of these positively selected mutations resulted in an increased potential to be phosphorylated in the Brazilian lineage compared to the African linage, which may have increased their potential to interfere with neural fetal development. CONCLUSIONS:ZIKV seems to have adapted to a limited number of hosts, including humans, during which its virulence increased. Its protein NS4B, together with NS4A, has recently been shown to inhibit Akt-mTOR signaling in human fetal neural stem cells, a key pathway for brain development. We hypothesize that positive selection of novel phosphorylation sites in the protein NS4B of the Brazilian lineage could interfere with phosphorylation of Akt and mTOR, impairing Akt-mTOR signaling and this may result in an increased risk for developmental neuropathies.

Dataset Information

In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus.

Publications

In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets