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It has been shown that hyperphosphorylated tau, a known AD pathological characteristic, is prematurely increased in the brains of HIV-infected individuals as early as in their 30s and that its levels increase with age. This suggests that HIV infection might lead to accelerated AD phenotypes. However, whether HIV infection causes AD to develop more quickly in the brain is not yet fully determined. Interestingly, we have previously revealed that the viral glycoproteins HIV gp120 and feline immunodeficiency virus (FIV) gp95 induce neuronal hyperexcitation via cGMP-dependent kinase II (cGKII; also known as PRKG2) activation in cultured hippocampal neurons. Here, we use cultured mouse cortical neurons to demonstrate that the presence of HIV gp120 and FIV gp95 are sufficient to increase cellular tau pathology, including intracellular tau hyperphosphorylation and tau release to the extracellular space. We further reveal that viral glycoprotein-induced cellular tau pathology requires cGKII activation. Taken together, HIV infection likely accelerates AD-related tau pathology via cGKII activation.<\/jats:p>","DOI":"10.1242\/jcs.259764","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T07:03:58Z","timestamp":1653980638000},"source":"Crossref","is-referenced-by-count":19,"title":["HIV and FIV glycoproteins increase cellular tau pathology via cGMP-dependent kinase II activation"],"prefix":"10.1242","volume":"135","author":[{"given":"Matheus F.","family":"Sathler","sequence":"first","affiliation":[{"name":"Colorado State University 1 Department of Biomedical Sciences, 1617 Campus Delivery , , Fort Collins, CO 80523 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Doolittle","sequence":"additional","affiliation":[{"name":"Colorado State University 2 Molecular, Cellular and Integrative Neurosciences Program , , Fort Collins, CO 80523 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Cockrell","sequence":"additional","affiliation":[{"name":"Colorado State University 3 Department of Human Development and Family Studies , , Fort Collins, CO 80523 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"India R.","family":"Nadalin","sequence":"additional","affiliation":[{"name":"Colorado State University 1 Department of Biomedical Sciences, 1617 Campus Delivery , , Fort Collins, CO 80523 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Technical University of Munich 4 , Arcisstra\u00dfe 21, D-80333 Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue","family":"VandeWoude","sequence":"additional","affiliation":[{"name":"Colorado State University 5 Department of Microbiology, Immunology, and Pathology , , Fort Collins, CO 80523 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0451-2180","authenticated-orcid":false,"given":"Seonil","family":"Kim","sequence":"additional","affiliation":[{"name":"Colorado State University 1 Department of Biomedical Sciences, 1617 Campus Delivery , , Fort Collins, CO 80523 , USA"},{"name":"Colorado State University 2 Molecular, Cellular and Integrative Neurosciences Program , , Fort Collins, CO 80523 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2022,6,21]]},"reference":[{"key":"2022070110025198000_JCS259764C1","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/S0006-8993(97)00166-2","article-title":"Acute rise in the concentration of free cytoplasmic calcium leads to dephosphorylation of the microtubule-associated protein tau","volume":"757","author":"Adamec","year":"1997","journal-title":"Brain Res."},{"key":"2022070110025198000_JCS259764C2","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1016\/j.mehy.2007.02.030","article-title":"The coming problem of HIV-associated Alzheimer's disease","volume":"69","author":"Alisky","year":"2007","journal-title":"Med. 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