Details
- Autor(en) / Beteiligte
- Titel
- Reduced-Beclin1-Expressing Mice Infected with Zika-R103451 and Viral-Associated Pathology during Pregnancy
- Ist Teil von
- Viruses, 2020-06, Vol.12 (6), p.608
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- EZB Electronic Journals Library
- Beschreibungen/Notizen
- Here, we used a mouse model with defective autophagy to further decipher the role of Beclin1 in the infection and disease of Zika virus (ZIKV)-R103451. Hemizygous ( ) and wild-type ( ) pregnant mice were transiently immunocompromised using the anti-interferon alpha/beta receptor subunit 1 monoclonal antibody MAR1-5A3. Despite a low mortality rate among the infected dams, 25% of offspring were smaller in size and had smaller, underdeveloped brains. This phenotype became apparent after 2-to 3-weeks post-birth. Furthermore, the smaller-sized pups showed a decrease in the mRNA expression levels of insulin-like growth factor (IGF)-1 and the expression levels of several microcephaly associated genes, when compared to their typical-sized siblings. Neuronal loss was also noticeable in brain tissues that were removed postmortem. Further analysis with murine mixed glia, derived from ZIKV-infected and pups, showed greater infectivity in glia derived from the genotype, along with a significant increase in pro-inflammatory molecules. In the present study, we identified a link by which defective autophagy is causally related to increased inflammatory molecules, reduced growth factor, decreased expression of microcephaly-associated genes, and increased neuronal loss. Specifically, we showed that a reduced expression of Beclin1 aggravated the consequences of ZIKV infection on brain development and qualifies as a susceptibility gene of ZIKV congenital syndrome.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1999-4915eISSN: 1999-4915DOI: 10.3390/v12060608Titel-ID: cdi_doaj_primary_oai_doaj_org_article_2538561aa7ca415eb0db38cebcccbc75
- Format
- –
- Schlagworte
- Animals, Autophagy, autophagy-defective mouse-model, Autopsy, Beclin-1 - genetics, Beclin-1 - metabolism, Beclin1, Brain, Brain - growth & development, Brain - metabolism, Brain - virology, Cell culture, Cell cycle, Cell division, Disease Models, Animal, Experiments, Female, Gene expression, Gene Knockdown Techniques, Genes, Genotypes, growth factor, Hemizygote, Humans, Infections, Infectivity, Inflammation, inflammatory molecules, Insulin, Insulin-Like Growth Factor I, Insulin-like growth factors, Interferon, Juveniles, Kinases, Laboratory animals, Male, Mice, Mice, Inbred C57BL, Microcephaly, Microencephaly, Monoclonal antibodies, Phagocytosis, Phenotypes, Pregnancy, Pregnancy Complications, Infectious - genetics, Pregnancy Complications, Infectious - metabolism, Pregnancy Complications, Infectious - pathology, Pregnancy Complications, Infectious - virology, Proteins, Tumor necrosis factor-TNF, Zika virus, Zika Virus - genetics, Zika Virus - physiology, Zika Virus Infection - genetics, Zika Virus Infection - metabolism, Zika Virus Infection - pathology, Zika Virus Infection - virology