Dataset Information

Zika virus infection accelerates Alzheimer's disease phenotypes in brain organoids.

ABSTRACT: Alzheimer's disease (AD) is one of the progressive neurodegenerative diseases characterized by β-amyloid (Aβ) production and Phosphorylated-Tau (p-Tau) protein in the cerebral cortex. The precise mechanisms of the cause, responsible for disease pathology and progression, are not well understood because there are multiple risk factors associated with the disease. Viral infection is one of the risk factors for AD, and we demonstrated that Zika virus (ZIKV) infection in brain organoids could trigger AD pathological features, including Aβ and p-Tau expression. AD-related phenotypes in brain organoids were upregulated via endoplasmic reticulum (ER) stress and unfolded protein response (UPR) after ZIKV infection in brain organoids. Under persistent ER stress, activated-double stranded RNA-dependent protein kinase-like ER-resident (PERK) triggered the phosphorylation of Eukaryotic initiation factor 2 (eIF2α) and then BACE, and GSK3α/β related to AD. Furthermore, we demonstrated that pharmacological inhibitors of PERK attenuated Aβ and p-Tau in brain organoids after ZIKV infection.

SUBMITTER: Lee SE

PROVIDER: S-EPMC8976422 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Zika virus infection accelerates Alzheimer's disease phenotypes in brain organoids.

Lee Seung-Eun SE Choi Hanul H Shin Nari N Kong Dasom D Kim Nam Gyo NG Kim Hee-Yeong HY Kim Min-Ji MJ Choi Soon Won SW Kim Young Bong YB Kang Kyung-Sun KS

Cell death discovery 20220402 1

Alzheimer's disease (AD) is one of the progressive neurodegenerative diseases characterized by β-amyloid (Aβ) production and Phosphorylated-Tau (p-Tau) protein in the cerebral cortex. The precise mechanisms of the cause, responsible for disease pathology and progression, are not well understood because there are multiple risk factors associated with the disease. Viral infection is one of the risk factors for AD, and we demonstrated that Zika virus (ZIKV) infection in brain organoids could trigge ...[more]

PMID: 35368019

Similar Datasets

Project description:Increasing the number of CpG dinucleotides in RNA viral genomes, while preserving the original amino acid composition, leads to impaired infection which does not cause disease. Beneficially, impaired infection evokes antiviral host immune responses providing a cutting-edge vaccine approach. For example, we previously showed that CpG-enriched Zika virus variants cause attenuated infection phenotypes and protect against lethal challenge in mice. While CpG recoding is an emerging and promising vaccine approach, little is known about infection phenotypes caused by recoded viruses in vivo, particularly in non-rodent species. Here, we used well-established mouse and porcine models to study infection phenotypes of the CpG-enriched neurotropic and congenital virus-Zika virus, directly in the target tissues-the brain and placenta. Specifically, we used the uttermost challenge and directly injected mice intracerebrally to compare infection phenotypes caused by wild-type and two CpG-recoded Zika variants and model the scenario where vaccine strains breach the blood-brain barrier. Also, we directly injected porcine fetuses to compare in utero infection phenotypes and model the scenario where recoded vaccine strains breach the placental barrier. While overall infection kinetics were comparable between wild-type and recoded virus variants, we found convergent phenotypical differences characterized by reduced pathology in the mouse brain and reduced replication of CpG-enriched variants in fetal lymph nodes. Next, using next-generation sequencing for the whole virus genome, we compared the stability of de novo introduced CpG dinucleotides during prolonged virus infection in the brain and placenta. Most de novo introduced CpG dinucleotides were preserved in sequences of recoded Zika viruses showing the stability of vaccine variants. Altogether, our study emphasized further directions to fine-tune the CpG recoding vaccine approach for better safety and can inform future immunization strategies.

Dataset Information

Zika virus infection accelerates Alzheimer's disease phenotypes in brain organoids.

Publications

Zika virus infection accelerates Alzheimer's disease phenotypes in brain organoids.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets