{"doi":"10.3390/v12060608","title":"Reduced-Beclin1-Expressing Mice Infected with Zika-R103451 and Viral-Associated Pathology during Pregnancy","abstract":"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 (Becn1+/−) and wild-type (Becn1+/+) 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 Becn1+/− 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 Becn1+/− and Becn1+/+ pups, showed greater infectivity in glia derived from the Becn1+/− 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 Becn1 as a susceptibility gene of ZIKV congenital syndrome.","journal":"Viruses","year":2020,"id":106372,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":513363,"name":"Chet Raj Ojha","orcid":"0000-0002-6816-8892","position":1,"is_corresponding":false},{"id":2415,"name":"Myosotys Rodriguez","orcid":"0000-0002-3925-9023","position":2,"is_corresponding":false},{"id":513364,"name":"Jessica Lapierre","orcid":"0000-0002-0606-9792","position":3,"is_corresponding":false},{"id":441735,"name":"M. Javad Aman","orcid":"0000-0001-6977-4707","position":4,"is_corresponding":false},{"id":396948,"name":"Fatah Kashanchi","orcid":"0000-0001-9681-2780","position":5,"is_corresponding":false},{"id":254218,"name":"Michał Toborek","orcid":"0000-0003-4475-2119","position":6,"is_corresponding":false},{"id":254216,"name":"Madhavan Nair","orcid":"0009-0009-9110-5337","position":7,"is_corresponding":false},{"id":364232,"name":"Nazira El‐Hage","orcid":"0000-0002-8154-6763","position":8,"is_corresponding":false},{"id":506266,"name":"Mohan Kumar Muthu Karuppan","orcid":"0000-0002-2795-5689","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-18T23:12:27.124515Z","pmid":"32498399","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}