{"id":{"repo_id":"gmu","oai_identifier":"oai:MARS:1920/15239"},"canonical_url":"https://search.dev.ndltd.org/etd/gmu/oai:MARS:1920/15239","repository":{"repo_id":"gmu","name":"George Mason University","base_url":"https://mars.gmu.edu/server/oai/request"},"display":{"title":"Comparing the Role of F07#13 in Transcription Inhibition by EZH2 Methylation in HIV-1-Infected Myeloid and T-Cells","abstract":"The human immunodeficiency virus 1 (HIV-1) is a retrovirus that has infected over seventy-five million individuals worldwide. This single-stranded RNA virus primarily infects CD4+ T-cells but can also infect other immune cells, such as myeloid cells. Many people living with HIV-1 (PLWH) take a cocktail of drugs called combination antiretroviral therapy (cART) to reduce HIV-1 viral load. However, these drugs do not eradicate HIV-1 viral reservoirs, which can still undergo transcription in cells. Thus, another means of treatment is needed to control viral transcription within immune cells and fully eradicate the infection. The Tat peptide mimetic, F07#13, has been demonstrated to inhibit viral transcription in HIV-1-infected T-cells and myeloid cells. F07#13 is known to bind to CDK9 and inhibit the CDK9/Tat/cyclin T1 complex. This process leads to Tat degradation and the production of non-coding RNAs, such as TAR-gag. These RNAs bind to Tat suppressive proteins. The suppressive complexes that TAR-gag bind to include Cul4B, and Sin3A, which all regulate HIV-1 gene expression. A previous paper published by our lab demonstrated the presence of PRC2 binding spots on TAR-gag RNAs. Therefore, we believe PRC2 may be a major player in transcription inhibition by F07#13 in infected cells. The catalytic component of PRC2, EZH2, plays a role in epigenetic silencing by methylating histone 3 at lysine 27. We sought to compare F07#13’s mechanism of inhibition in infected T-cells and myeloid cells and to identify differences in EZH2 levels in these cell types after F07#13 treatment. First, we identified that F07#13 decreases cell viability over time. We then discovered greater efficacy of transcription inhibition in infected myeloid cells (U1) compared to T-cells (J1.1) by F07#13. We also identified that PRC2 plays a greater role in transcription inhibition in infected T-cells compared to myeloid cells.","abstract_html":"The human immunodeficiency virus 1 (HIV-1) is a retrovirus that has infected over seventy-five million individuals worldwide. This single-stranded RNA virus primarily infects CD4+ T-cells but can also infect other immune cells, such as myeloid cells. Many people living with HIV-1 (PLWH) take a cocktail of drugs called combination antiretroviral therapy (cART) to reduce HIV-1 viral load. However, these drugs do not eradicate HIV-1 viral reservoirs, which can still undergo transcription in cells. Thus, another means of treatment is needed to control viral transcription within immune cells and fully eradicate the infection. The Tat peptide mimetic, F07#13, has been demonstrated to inhibit viral transcription in HIV-1-infected T-cells and myeloid cells. F07#13 is known to bind to CDK9 and inhibit the CDK9/Tat/cyclin T1 complex. This process leads to Tat degradation and the production of non-coding RNAs, such as TAR-gag. These RNAs bind to Tat suppressive proteins. The suppressive complexes that TAR-gag bind to include Cul4B, and Sin3A, which all regulate HIV-1 gene expression. A previous paper published by our lab demonstrated the presence of PRC2 binding spots on TAR-gag RNAs. Therefore, we believe PRC2 may be a major player in transcription inhibition by F07#13 in infected cells. The catalytic component of PRC2, EZH2, plays a role in epigenetic silencing by methylating histone 3 at lysine 27. We sought to compare F07#13’s mechanism of inhibition in infected T-cells and myeloid cells and to identify differences in EZH2 levels in these cell types after F07#13 treatment. First, we identified that F07#13 decreases cell viability over time. We then discovered greater efficacy of transcription inhibition in infected myeloid cells (U1) compared to T-cells (J1.1) by F07#13. We also identified that PRC2 plays a greater role in transcription inhibition in infected T-cells compared to myeloid cells.","abstract_has_math":false,"creators":["Arthur, Benjamina"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025","date_published":"2025","updated_at":"2026-07-27T19:51:46Z","subjects":["Combination antiretroviral therapy","F07#13","HIV-1","Myeloid cell","T-cell","Transcription inhibitor"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:1920/15239"],"render_values":[{"text":"hdl:1920/15239","href":null,"code":true}]}]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2025"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Combination antiretroviral therapy","F07#13","HIV-1","Myeloid cell","T-cell","Transcription inhibitor"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:1920/15239"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.other","label":"Dc Description Other","values":["The human immunodeficiency virus 1 (HIV-1) is a retrovirus that has infected over seventy-five million individuals worldwide. This single-stranded RNA virus primarily infects CD4+ T-cells but can also infect other immune cells, such as myeloid cells. Many people living with HIV-1 (PLWH) take a cocktail of drugs called combination antiretroviral therapy (cART) to reduce HIV-1 viral load. However, these drugs do not eradicate HIV-1 viral reservoirs, which can still undergo transcription in cells. Thus, another means of treatment is needed to control viral transcription within immune cells and fully eradicate the infection. The Tat peptide mimetic, F07#13, has been demonstrated to inhibit viral transcription in HIV-1-infected T-cells and myeloid cells. F07#13 is known to bind to CDK9 and inhibit the CDK9/Tat/cyclin T1 complex. This process leads to Tat degradation and the production of non-coding RNAs, such as TAR-gag. These RNAs bind to Tat suppressive proteins. The suppressive complexes that TAR-gag bind to include Cul4B, and Sin3A, which all regulate HIV-1 gene expression. A previous paper published by our lab demonstrated the presence of PRC2 binding spots on TAR-gag RNAs. Therefore, we believe PRC2 may be a major player in transcription inhibition by F07#13 in infected cells. The catalytic component of PRC2, EZH2, plays a role in epigenetic silencing by methylating histone 3 at lysine 27. We sought to compare F07#13’s mechanism of inhibition in infected T-cells and myeloid cells and to identify differences in EZH2 levels in these cell types after F07#13 treatment. First, we identified that F07#13 decreases cell viability over time. We then discovered greater efficacy of transcription inhibition in infected myeloid cells (U1) compared to T-cells (J1.1) by F07#13. We also identified that PRC2 plays a greater role in transcription inhibition in infected T-cells compared to myeloid cells."]},{"key":"dc:title","label":"Title","values":["Comparing the Role of F07#13 in Transcription Inhibition by EZH2 Methylation in HIV-1-Infected Myeloid and T-Cells"]}]}],"canonical_facts":{"dc:date.issued":["2025"],"dc:description.other":["The human immunodeficiency virus 1 (HIV-1) is a retrovirus that has infected over seventy-five million individuals worldwide. This single-stranded RNA virus primarily infects CD4+ T-cells but can also infect other immune cells, such as myeloid cells. Many people living with HIV-1 (PLWH) take a cocktail of drugs called combination antiretroviral therapy (cART) to reduce HIV-1 viral load. However, these drugs do not eradicate HIV-1 viral reservoirs, which can still undergo transcription in cells. Thus, another means of treatment is needed to control viral transcription within immune cells and fully eradicate the infection. The Tat peptide mimetic, F07#13, has been demonstrated to inhibit viral transcription in HIV-1-infected T-cells and myeloid cells. F07#13 is known to bind to CDK9 and inhibit the CDK9/Tat/cyclin T1 complex. This process leads to Tat degradation and the production of non-coding RNAs, such as TAR-gag. These RNAs bind to Tat suppressive proteins. The suppressive complexes that TAR-gag bind to include Cul4B, and Sin3A, which all regulate HIV-1 gene expression. A previous paper published by our lab demonstrated the presence of PRC2 binding spots on TAR-gag RNAs. Therefore, we believe PRC2 may be a major player in transcription inhibition by F07#13 in infected cells. The catalytic component of PRC2, EZH2, plays a role in epigenetic silencing by methylating histone 3 at lysine 27. We sought to compare F07#13’s mechanism of inhibition in infected T-cells and myeloid cells and to identify differences in EZH2 levels in these cell types after F07#13 treatment. First, we identified that F07#13 decreases cell viability over time. We then discovered greater efficacy of transcription inhibition in infected myeloid cells (U1) compared to T-cells (J1.1) by F07#13. We also identified that PRC2 plays a greater role in transcription inhibition in infected T-cells compared to myeloid cells."],"dc:identifier":["hdl:1920/15239"],"dc:subject":["Combination antiretroviral therapy","F07#13","HIV-1","Myeloid cell","T-cell","Transcription inhibitor"],"dc:title":["Comparing the Role of F07#13 in Transcription Inhibition by EZH2 Methylation in HIV-1-Infected Myeloid and T-Cells"],"dc:type":["Thesis"]},"updated_at":"2026-07-27T19:51:46Z"}