{"doi":"10.3390/v16050693","title":"EcoHIV Infection of Primary Murine Brain Cell Cultures to Model HIV Replication and Neuropathogenesis","abstract":"<jats:p>Background. EcoHIV is a chimeric HIV that replicates in mice in CD4+ T cells, macrophages, and microglia (but not in neurons), causing lasting neurocognitive impairment resembling neurocognitive disease in people living with HIV. The present study was designed to develop EcoHIV-susceptible primary mouse brain cultures to investigate the indirect effects of HIV infection on neuronal integrity. Results. We used two EcoHIV clones encoding EGFP and mouse bone marrow-derived macrophages (BMM), mixed mouse brain cells, or enriched mouse glial cells from two wild-type mouse strains to test EcoHIV replication efficiency, the identity of productively infected cells, and neuronal apoptosis and integrity. EcoHIV replicated efficiently in BMM. In mixed brain cell cultures, EcoHIV targeted microglia but did not cause neuronal apoptosis. Instead, the productive infection of the microglia activated them and impaired synaptophysin expression, dendritic density, and axonal structure in the neurons. EcoHIV replication in the microglia and neuronal structural changes during infection were prevented by culture with an antiretroviral. Conclusions. In murine brain cell cultures, EcoHIV replication in the microglia is largely responsible for the aspects of neuronal dysfunction relevant to cognitive disease in infected mice and people living with HIV. These cultures provide a tool for further study of HIV neuropathogenesis and its control.</jats:p>","journal":"Viruses","year":2024,"id":688438,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":461372,"name":"Wei Chao","orcid":"0000-0002-2505-1360","position":1,"is_corresponding":false},{"id":69438,"name":"Eran Hadas","orcid":"0000-0001-7966-8326","position":2,"is_corresponding":false},{"id":69433,"name":"Alejandra Borjabad","orcid":"0000-0001-5479-5644","position":3,"is_corresponding":false},{"id":419476,"name":"Mary Jane Potash","orcid":"0000-0002-4640-8269","position":4,"is_corresponding":false},{"id":69478,"name":"David J. Volsky","orcid":"0000-0001-6788-1752","position":5,"is_corresponding":false},{"id":901966,"name":"Boe‐Hyun Kim","orcid":"0000-0003-2821-0467","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"EcoHIV Infection of Primary Murine Brain Cell Cultures to Model HIV Replication and Neuropathogenesis","abstract":"<jats:p>Background. EcoHIV is a chimeric HIV that replicates in mice in CD4+ T cells, macrophages, and microglia (but not in neurons), causing lasting neurocognitive impairment resembling neurocognitive disease in people living with HIV. The present study was designed to develop EcoHIV-susceptible primary mouse brain cultures to investigate the indirect effects of HIV infection on neuronal integrity. Results. We used two EcoHIV clones encoding EGFP and mouse bone marrow-derived macrophages (BMM), mixed mouse brain cells, or enriched mouse glial cells from two wild-type mouse strains to test EcoHIV replication efficiency, the identity of productively infected cells, and neuronal apoptosis and integrity. EcoHIV replicated efficiently in BMM. In mixed brain cell cultures, EcoHIV targeted microglia but did not cause neuronal apoptosis. Instead, the productive infection of the microglia activated them and impaired synaptophysin expression, dendritic density, and axonal structure in the neurons. EcoHIV replication in the microglia and neuronal structural changes during infection were prevented by culture with an antiretroviral. Conclusions. In murine brain cell cultures, EcoHIV replication in the microglia is largely responsible for the aspects of neuronal dysfunction relevant to cognitive disease in infected mice and people living with HIV. These cultures provide a tool for further study of HIV neuropathogenesis and its control.</jats:p>","is_dataset_classified":null,"base_score":2.772588722239781,"endowment":2.772588722239781,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38793575","pmcid":null,"openalex_id":"https://openalex.org/W4396585473","authors":[],"funders":[{"funder_name":"PHS","grant_id":"R01DA037611","title":null},{"funder_name":"PHS","grant_id":"R01NS117458","title":null},{"funder_name":"PHS","grant_id":"RF1R01NS119438","title":null},{"funder_name":"PHS","grant_id":"R01DA052844","title":null},{"funder_name":"PHS","grant_id":"U01DA053629","title":null},{"funder_name":"PHS","grant_id":"U01DA056003","title":null},{"funder_name":"PHS","grant_id":"NS129460","title":null},{"funder_name":"National Institutes of Health","grant_id":"5U01DA056003-02","title":"Single cell transcriptomic and epigenomic changes during chronic HIV infection and cocaine self-administration"},{"funder_name":"National Institutes of Health","grant_id":"4R01NS119438-02","title":"Routes to Enhanced HIV Neuropathogenesis Through Expression of Subclinical Levels of Endogenous Amyloid-Beta"},{"funder_name":"National Institutes of Health","grant_id":"1R01NS117458-01","title":"Host Glycomic Modulation of HIV-associated Neuro-inflammation During Viral Suppression"},{"funder_name":"National Institutes of Health","grant_id":"1R21NS129460-01","title":"Functional Cure of HIV Neurocognitive Disease by Induction of Innate Immunity"},{"funder_name":"National Institutes of Health","grant_id":"5U01DA053629-05","title":"Single cell brain transcriptome changes during chronic HIV infection and opiate use in conventional mice"},{"funder_name":"National Institutes of Health","grant_id":"5R01DA037611-05","title":"Threshold of Cognitive Impairment after HIV Infection: Effect of Morphine"},{"funder_name":"National Institutes of Health","grant_id":"5R01DA052844-03","title":"Mechanism of Cannabidiol Effects on HIV Expression, Neuroinflammation, and HIV Cognitive Disease in Chronically-infected Immunocompetent Mice"},{"funder_name":"NINDS NIH HHS","grant_id":"R21 129460","title":null}],"total_grants":15,"fwci":3.3927,"citation_percentile":0.92739922,"influential_citations":0,"citation_trend":[{"year":2024,"count":4},{"year":2025,"count":6},{"year":2026,"count":5}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.3390/v16050693","host_type":"journal"},{"url":"https://doi.org/10.3390/v16050693","host_type":"publisher"},{"url":"https://www.mdpi.com/1999-4915/16/5/693/pdf","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38793575","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11125688","host_type":"repository"},{"url":"https://doaj.org/article/42803026dcbb44a69cbf016bca261017","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11125688/pdf/viruses-16-00693.pdf","host_type":"repository"},{"url":"http://dx.doi.org/10.3390/v16050693","host_type":""},{"url":"https://dx.doi.org/10.3390/v16050693","host_type":""}],"fields_of_study":["HIV Research and Treatment","Neuroinflammation and Neurodegeneration Mechanisms","Tryptophan and brain disorders","0301 basic medicine","0303 health sciences","03 medical and health sciences","Animals","Mice","Virus Replication","Brain","Neurons","Microglia","Cells, Cultured","HIV Infections","Macrophages","Disease Models, Animal","Apoptosis","Humans","HIV-1","Primary Cell Culture","Mice, Inbred C57BL"],"mesh_terms":["Animals","Brain","Cells, Cultured","Disease Models, Animal","Humans","Macrophages","Mice, Inbred C57BL","Neurons","Virus Replication","HIV-1","HIV Infections","Apoptosis","Microglia","Mice","Primary Cell Culture"],"keywords":["Virology","Human immunodeficiency virus (HIV)","Replication (statistics)","Viral replication","Primary (astronomy)","Biology","Brain Cell","Immunology","Neuroscience","Virus","Physics","primary brain cell cultures","Neurons","Macrophages","Primary Cell Culture","Brain","HIV Infections","Apoptosis","HIV infection","Virus Replication","Microbiology","QR1-502","Article","Mice, Inbred C57BL","Mice","Disease Models, Animal","neuropathogenesis","HIV-1","Animals","Humans","Microglia","Cells, Cultured"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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