{"doi":"10.1101/2021.09.02.458765","title":"Neurodevelopmental processes in the prefrontal cortex derailed by chronic HIV-1 viral protein exposure","abstract":"Abstract Due to the widespread access to, and implementation of, combination antiretroviral therapy, individuals perinatally infected with human immunodeficiency virus type 1 (HIV-1) are living into adolescence and adulthood. Perinatally infected adolescents living with HIV-1 (pALHIV) are plagued by progressive, chronic neurocognitive impairments; the pathophysiological mechanisms underlying these deficits, however, remains understudied. A longitudinal experimental design from postnatal day (PD) 30 to PD 180 was utilized to establish the development of pyramidal neurons, and associated dendritic spines, from layers II-III of the medial prefrontal cortex (mPFC). Three putative neuroinflammatory markers (i.e., IL-1β, IL-6, and TNF-α) were evaluated early in development (i.e., PD 30) as a potential mechanism underlying synaptic dysfunction in the mPFC. Constitutive expression of HIV-1 viral proteins induced prominent neurodevelopmental alterations, independent of biological sex, in pyramidal neurons from layers II-III of the mPFC. Specifically, HIV-1 transgenic rats exhibited prominent deficits in dendritic and synaptic pruning, a developmental decrease in synaptic connectivity, and an age-related decline in synaptic efficacy. Examination of dendritic spine morphology revealed an age-related population shift towards a more immature dendritic spine phenotype in HIV-1 transgenic animals. There was no compelling evidence for neuroinflammation in the mPFC during early development. Understanding the neural mechanisms underlying chronic neurocognitive impairments in pALHIV may afford a key target for innovative therapeutics and cure strategies; an urgent need given the growing population of pALHIV.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":219261,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":310823,"name":"Hailong Li","orcid":"0000-0002-5267-2875","position":1,"is_corresponding":false},{"id":576867,"name":"Rosemarie M. Booze","orcid":"0000-0003-3908-8313","position":2,"is_corresponding":false},{"id":576866,"name":"Charles F. Mactutus","orcid":"0000-0002-6508-1329","position":3,"is_corresponding":false},{"id":576864,"name":"Kristen A. McLaurin","orcid":"0000-0001-7816-1806","position":0,"is_corresponding":true}],"reference_count":126,"raw_metadata":null,"created_at":"2026-07-18T23:53:38.409982Z","pmid":null,"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":[]}