{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T18:06:36Z","timestamp":1771524396576,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T00:00:00Z","timestamp":1671062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC8187108"],"award-info":[{"award-number":["NSFC8187108"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2018SK2090"],"award-info":[{"award-number":["2018SK2090"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2020JJ5701"],"award-info":[{"award-number":["2020JJ5701"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Research and Development Program of Hunan Province","award":["NSFC8187108"],"award-info":[{"award-number":["NSFC8187108"]}]},{"name":"Key Research and Development Program of Hunan Province","award":["2018SK2090"],"award-info":[{"award-number":["2018SK2090"]}]},{"name":"Key Research and Development Program of Hunan Province","award":["2020JJ5701"],"award-info":[{"award-number":["2020JJ5701"]}]},{"name":"Natural Science Foundation of Hunan\u2014Youth Foundation Project","award":["NSFC8187108"],"award-info":[{"award-number":["NSFC8187108"]}]},{"name":"Natural Science Foundation of Hunan\u2014Youth Foundation Project","award":["2018SK2090"],"award-info":[{"award-number":["2018SK2090"]}]},{"name":"Natural Science Foundation of Hunan\u2014Youth Foundation Project","award":["2020JJ5701"],"award-info":[{"award-number":["2020JJ5701"]}]},{"name":"Central South University","award":["NSFC8187108"],"award-info":[{"award-number":["NSFC8187108"]}]},{"name":"Central South University","award":["2018SK2090"],"award-info":[{"award-number":["2018SK2090"]}]},{"name":"Central South University","award":["2020JJ5701"],"award-info":[{"award-number":["2020JJ5701"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human immunodeficiency virus-1 (HIV-1)-associated neurodegenerative disorder (HAND) is frequently reported in HIV-infected individuals. The gp120 envelope viral protein has been implicated in the pathogenesis of HAND in HIV-1-infected patients; however, its pathogenic mechanism remains unclear. In this study, we first overexpressed gp120 proteins in pc12 cells and used PI staining, a CCK8 assay, a TUNEL assay, and caspase-9\/caspase-3-induced apoptosis to ascertain the mediated cell death. Subsequently, the gp120-overexpressed cells were subjected to RNA transcriptomics and mass spectrometry. The obtained results were integrated and validated using a quantitative polymerase chain reaction (qPCR) and the postmortem brain samples with HIV-associated dementia were analyzed against the normal control (using the GSE35864 data set on gene ontology omnibus repository). Upon the integration of the RNA transcriptomic and proteomic results, 78 upregulated genes were revealed. Fut8, Unc13c, Cdk1, Loc100359539, and Hspa2 were the top five upregulated genes. Upon the analysis of the GSE35864 data set, the results indicate that Cdk1 was upregulated in HIV-associated dementia in comparison to the normal control. Moreover, the protein expression of Cdk1 was significantly higher in the gp120 transfected group compared to the normal control and decreased significantly upon inhibition using Roscovitine (a known Cdk1 inhibitor). Taken together, our results provide a possible molecular signature of the neurological impairment secondary to HIV glycoprotein 120.<\/jats:p>","DOI":"10.3390\/v14122793","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T02:20:57Z","timestamp":1671070857000},"page":"2793","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["HIV-1 gp120 Protein Activates Cyclin-Dependent Kinase 1, a Possible Link to Central Nervous System Cell Death"],"prefix":"10.3390","volume":"14","author":[{"given":"Adonira","family":"Saro","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaolin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2436-0943","authenticated-orcid":false,"given":"Piniel Alphayo","family":"Kambey","sequence":"additional","affiliation":[{"name":"Xuzhou Key Laboratory of Neurobiology, Department of Neurobiology and Anatomy, Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jufang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, China"},{"name":"School of Life Sciences, Central South University, Changsha 410013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/ana.410190603","article-title":"The AIDS Dementia Complex: II. Neuropathology","volume":"19","author":"Navia","year":"1986","journal-title":"Ann. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrneurol.2016.27","article-title":"HIV-Associated Neurocognitive Disorder\u2014Pathogenesis and Prospects for Treatment","volume":"12","author":"Saylor","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/ana.410190602","article-title":"The AIDS Dementia Complex: I. Clinical Features","volume":"19","author":"Navia","year":"1986","journal-title":"Ann. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1080\/07853890.2020.1814962","article-title":"Important Role of Microglia in HIV-1 Associated Neurocognitive Disorders and the Molecular Pathways Implicated in Its Pathogenesis","volume":"53","author":"Borrajo","year":"2021","journal-title":"Ann. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1097\/QAD.0b013e3283391d56","article-title":"HIV-Associated Neurocognitive Disorders: Is There a Hidden Epidemic?","volume":"24","author":"McArthur","year":"2010","journal-title":"AIDS"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1038\/s41467-017-01795-8","article-title":"HIV-1 Counteracts an Innate Restriction by Amyloid Precursor Protein Resulting in Neurodegeneration","volume":"8","author":"Chai","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1128\/JVI.73.1.205-213.1999","article-title":"Microglia Express CCR5, CXCR4, and CCR3, but of These, CCR5 Is the Principal Coreceptor for Human Immunodeficiency Virus Type 1 Dementia Isolates","volume":"73","author":"Albright","year":"1999","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1046\/j.1471-4159.2003.01775.x","article-title":"MCP-1 (CCL2) Protects Human Neurons and Astrocytes from NMDA or HIV-Tat-Induced Apoptosis","volume":"85","author":"Eugenin","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1038\/sj.jcbfm.9600115","article-title":"Signaling Mechanisms of HIV-1 Tat-Induced Alterations of Claudin-5 Expression in Brain Endothelial Cells","volume":"25","author":"Pu","year":"2005","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"317","DOI":"10.2353\/jmoldx.2008.070074","article-title":"Successful Application of Hyperbranched Multidisplacement Genomic Amplification to Detect HIV-1 Sequences in Single Neurons Removed from Autopsy Brain Sections by Laser Capture Microdissection","volume":"10","author":"Petito","year":"2008","journal-title":"J. Mol. Diagn."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Chi, X., Amet, T., Byrd, D., Chang, K.-H., Shah, K., Hu, N., Grantham, A., Hu, S., Duan, J., and Tao, F. (2011). Direct Effects of HIV-1 Tat on Excitability and Survival of Primary Dorsal Root Ganglion Neurons: Possible Contribution to HIV-1-Associated Pain. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024412"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1742-6405-11-13","article-title":"Viral and Cellular Factors Underlying Neuropathogenesis in HIV Associated Neurocognitive Disorders (HAND)","volume":"11","author":"Rao","year":"2014","journal-title":"AIDS Res. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"079","DOI":"10.1385\/JMN:27:1:079","article-title":"HIV-1 Infection of Neurons Might Account for Progressive HIV-1-Associated Encephalopathy in Children","volume":"27","author":"Lacruz","year":"2005","journal-title":"J. Mol. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/35073667","article-title":"Pathways to Neuronal Injury and Apoptosis in HIV-Associated Dementia","volume":"410","author":"Kaul","year":"2001","journal-title":"Nature"},{"key":"ref_15","first-page":"2152","article-title":"Unusual Fusion Proteins of HIV-1","volume":"7","author":"Langer","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1093\/brain\/awm195","article-title":"Characterization of Rodent Models of HIV-Gp120 and Anti-Retroviral-Associated Neuropathic Pain","volume":"130","author":"Wallace","year":"2007","journal-title":"Brain"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"369","DOI":"10.2174\/157016212802138724","article-title":"HIV-1 Gp120 and Drugs of Abuse: Interactions in the Central Nervous System","volume":"10","author":"Silverstein","year":"2012","journal-title":"Curr. HIV Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"741","DOI":"10.2174\/092986710790514499","article-title":"The GP120 Molecule of HIV-1 and Its Interaction with T Cells","volume":"17","author":"Yoon","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11047","DOI":"10.1523\/JNEUROSCI.2733-07.2007","article-title":"Human Immunodeficiency Virus-1\/Surface Glycoprotein 120 Induces Apoptosis through RNA-Activated Protein Kinase Signaling in Neurons","volume":"27","author":"Alirezaei","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"18929","DOI":"10.1038\/srep18929","article-title":"HIV-1 Gp120 Induces Type-1 Programmed Cell Death through ER Stress Employing IRE1\u03b1, JNK and AP-1 Pathway","volume":"6","author":"Shah","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Shah, A., Verma, A.S., Patel, K.H., Noel, R., Rivera-Amill, V., Silverstein, P.S., Chaudhary, S., Bhat, H.K., Stamatatos, L., and Singh, D.P. (2011). HIV-1 Gp120 Induces Expression of IL-6 through a Nuclear Factor-Kappa B-Dependent Mechanism: Suppression by Gp120 Specific Small Interfering RNA. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021261"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression Omnibus: NCBI Gene Expression and Hybridization Array Data Repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wu, J., Kharebava, G., Piao, C., Stoica, B.A., Dinizo, M., Sabirzhanov, B., Hanscom, M., Guanciale, K., and Faden, A.I. (2012). Inhibition of E2F1\/CDK1 Pathway Attenuates Neuronal Apoptosis in Vitro and Confers Neuroprotection after Spinal Cord Injury in Vivo. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042129"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wiatrak, B., Kubis-Kubiak, A., Piwowar, A., and Barg, E. (2020). PC12 Cell Line: Cell Types, Coating of Culture Vessels, Differentiation and Other Culture Conditions. Cells, 9.","DOI":"10.3390\/cells9040958"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9407","DOI":"10.1128\/JVI.76.18.9407-9419.2002","article-title":"Development of a Human Neuronal Cell Model for Human Immunodeficiency Virus (HIV)-Infected Macrophage-Induced Neurotoxicity: Apoptosis Induced by HIV Type 1 Primary Isolates and Evidence for Involvement of the Bcl-2\/Bcl-XL-Sensitive Intrinsic Apoptosis P","volume":"76","author":"Chen","year":"2002","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Chen, L., Liu, J., Xu, C., Keblesh, J., Zang, W., and Xiong, H. (2011). HIV-1gp120 Induces Neuronal Apoptosis through Enhancement of 4-Aminopyridine-Senstive Outward K+ Currents. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025994"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1523\/JNEUROSCI.23-07-02557.2003","article-title":"Neuronal Cell Death Is Preceded by Cell Cycle Events at All Stages of Alzheimer\u2019s Disease","volume":"23","author":"Yang","year":"2003","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/nrn2124","article-title":"Cell Cycle Regulation in the Postmitotic Neuron: Oxymoron or New Biology?","volume":"8","author":"Herrup","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5643","DOI":"10.1242\/jcs.01486","article-title":"Contagious Apoptosis Facilitated by the HIV-1 Envelope: Fusion-Induced Cell-to-Cell Transmission of a Lethal Signal","volume":"117","author":"Andreau","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1091\/mbc.e08-07-0771","article-title":"Fine Tuning the Cell Cycle: Activation of the Cdk1 Inhibitory Phosphorylation Pathway during Mitotic Exit","volume":"20","author":"Potapova","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1006\/excr.1996.0356","article-title":"Dynamic Changes in Nuclear Architecture during Mitosis: On the Role of Protein Phosphorylation in Spindle Assembly and Chromosome Segregation","volume":"229","author":"Nigg","year":"1996","journal-title":"Exp. Cell Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108381","DOI":"10.1016\/j.steroids.2019.02.014","article-title":"Upregulated Cyclin B1\/CDK1 Mediates Apoptosis Following 2-Methoxyestradiol-Induced Mitotic Catastrophe: Role of Bcl-X(L) Phosphorylation","volume":"150","author":"Choi","year":"2019","journal-title":"Steroids"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s13048-017-0356-x","article-title":"The Aberrant Upstream Pathway Regulations of CDK1 Protein Were Implicated in the Proliferation and Apoptosis of Ovarian Cancer Cells","volume":"10","author":"Zhang","year":"2017","journal-title":"J. Ovarian Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2174\/1570162X13666150311164201","article-title":"Mechanisms of HIV-1 Tat Neurotoxicity via CDK5 Translocation and Hyper-Activation: Role in HIV-Associated Neurocognitive Disorders","volume":"13","author":"Fields","year":"2015","journal-title":"Curr. HIV Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1038\/sj.cdd.4401130","article-title":"Cyclin-Dependent Kinase-1: Linking Apoptosis to Cell Cycle and Mitotic Catastrophe","volume":"9","author":"Castedo","year":"2002","journal-title":"Cell Death Differ."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4070","DOI":"10.1093\/emboj\/cdf391","article-title":"Sequential Involvement of Cdk1, MTOR and P53 in Apoptosis Induced by the HIV-1 Envelope","volume":"21","author":"Castedo","year":"2002","journal-title":"EMBO J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1038\/jcbfm.2008.75","article-title":"Roscovitine Reduces Neuronal Loss, Glial Activation, and Neurologic Deficits after Brain Trauma","volume":"28","author":"Hilton","year":"2008","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8333","DOI":"10.1073\/pnas.0500989102","article-title":"Cell Cycle Inhibition Provides Neuroprotection and Reduces Glial Proliferation and Scar Formation after Traumatic Brain Injury","volume":"102","author":"Movsesyan","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/12\/2793\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:41:38Z","timestamp":1760146898000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/12\/2793"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,15]]},"references-count":38,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["v14122793"],"URL":"https:\/\/doi.org\/10.3390\/v14122793","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,15]]}}}