{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T13:57:49Z","timestamp":1768831069647,"version":"3.49.0"},"reference-count":55,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T00:00:00Z","timestamp":1694649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DA057884"],"award-info":[{"award-number":["DA057884"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["MH118985"],"award-info":[{"award-number":["MH118985"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DA057145"],"award-info":[{"award-number":["DA057145"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The protein Beclin1 (BECN1, a mammalian homologue of ATG6 in yeast) plays an important role in the initiation and the normal process of autophagy in cells. Moreover, we and others have shown that Beclin1 plays an important role in viral replication and the innate immune signaling pathways. We previously used the cationic polymer polyethyleneimine (PEI) conjugated to mannose (Man) as a non-viral tool for the delivery of a small interfering (si) Beclin1-PEI-Man nanoplex, which specifically targets mannose receptor-expressing glia (microglia and astrocytes) in the brain when administered intranasally to conventional mice. To expand our previous reports, first we used C57BL\/6J mice infected with EcoHIV and exposed them to combined antiretroviral therapy (cART). We show that EcoHIV enters the mouse brain, while intranasal delivery of the nanocomplex significantly reduces the secretion of HIV-induced inflammatory molecules and downregulates the expression of the transcription factor nuclear factor (NF)-kB. Since a spectrum of neurocognitive and motor problems can develop in people living with HIV (PLWH) despite suppressive antiretroviral therapy, we subsequently measured the role of Beclin1 in locomotor activities using EcoHIV-infected BECN1 knockout mice exposed to cART. Viral replication and cytokine secretion were reduced in the postmortem brains recovered from EcoHIV-infected Becn1+\/\u2212 mice when compared to EcoHIV-infected Becn1+\/+ mice, although the impairment in locomotor activities based on muscle strength were comparable. This further highlights the importance of Beclin1 in the regulation of HIV replication and in viral-induced cytokine secretion but not in HIV-induced locomotor impairments. Moreover, the cause of HIV-induced locomotor impairments remains speculative, as we show that this may not be entirely due to viral load and\/or HIV-induced inflammatory cytokines.<\/jats:p>","DOI":"10.3390\/v15091923","type":"journal-article","created":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T03:50:10Z","timestamp":1694749810000},"page":"1923","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Implication of the Autophagy-Related Protein Beclin1 in the Regulation of EcoHIV Replication and Inflammatory Responses"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3925-9023","authenticated-orcid":false,"given":"Myosotys","family":"Rodriguez","sequence":"first","affiliation":[{"name":"Department of Immunology and Nanomedicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florida","family":"Owens","sequence":"additional","affiliation":[{"name":"Department of Immunology and Nanomedicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marissa","family":"Perry","sequence":"additional","affiliation":[{"name":"Department of Immunology and Nanomedicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Stone","sequence":"additional","affiliation":[{"name":"Department of Immunology and Nanomedicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yemmy","family":"Soler","sequence":"additional","affiliation":[{"name":"Department of Immunology and Nanomedicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rianna","family":"Almohtadi","sequence":"additional","affiliation":[{"name":"Department of Immunology and Nanomedicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuling","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9386-3790","authenticated-orcid":false,"given":"Elena V.","family":"Batrakova","sequence":"additional","affiliation":[{"name":"Center for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazira","family":"El-Hage","sequence":"additional","affiliation":[{"name":"Department of Immunology and Nanomedicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1212\/WNL.0b013e318200d727","article-title":"HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study","volume":"75","author":"Heaton","year":"2010","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1097\/QAD.0b013e3283354a7b","article-title":"Cognitive dysfunction in HIV patients despite long-standing suppression of viremia","volume":"24","author":"Simioni","year":"2010","journal-title":"AIDS"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1080\/13550280490521078","article-title":"Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus-infected\/acquired immunodeficiency syndrome (HIV\/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: A combined study of two cohorts","volume":"10","author":"Cysique","year":"2004","journal-title":"J. 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