[{"key":"dc.contributor.author","value":"Lam, Cindy Hei Yiu","language":null},{"key":"dc.date.accessioned","value":"2025-03-27T18:31:39Z","language":null},{"key":"dc.date.available","value":"2026-03-31T07:00:00Z","language":null},{"key":"dc.date.issued","value":"2025","language":"en"},{"key":"dc.identifier.uri","value":"http:\/\/hdl.handle.net\/2429\/90541","language":null},{"key":"dc.description.abstract","value":"Advancements in antiretroviral therapies have drastically altered the outlook of the HIV epidemic, however there is no cure. The main obstacle to a cure is the population of cells harbouring transcriptionally silent, chromosomally integrated provirus. These latently infected cells proliferate into reservoirs of HIV-1 that are undetectable by the immune system, and are unaffected by ART, until they reactivate, leading to viral rebound. As such, strategies have been devised to selectively target these cells, through provirus reactivation and subsequent elimination by the immune system, or through permanent suppression of proviral transcription. However, a more complete understanding of the mechanisms behind viral latency are required for these strategies to succeed. This work focuses on three factors involved in viral latency.\r\nIn HIV-1 infection, mTORC1 is upregulated to allow for efficient viral replication and inhibitors of mTORC1 are known to prevent reactivation in latently infected cells. Through an shRNA screen against known drug targets and previous research into TOR signalling in yeast, we discovered a connection between aspartate and mTORC1. In this work, we show that cell permeable aspartate analogs suppress reactivation of latent infection in CD4+ T cells through inhibition of mTORC1 signaling, highlighting the potential of aspartate or cell permeable analogs as therapeutics for suppression of latent infection. \r\nYY1 is a transcription factor that interacts with the HIV-1 promoter in latently infected cells. However, it has been suggested that it suppresses expression through multiple mechanisms, therefore we investigated its role in T cell activation state, another key factor in regulation of HIV-1 expression, identifying its protein interactors in resting and activated T cells. \r\nFinally, Nef is an accessory protein encoded by the HIV-1 genome. It is vital  for pathogenesis, but not required for efficient replication in cell culture. Thus, it has been excluded from many models of HIV-1 infection and its role in latency establishment was unknown. In this thesis, we developed a novel reporter system including Nef that could provide further insight into mechanisms regulating latency, and we show that Nef does not alter the ability of infected cells to establish immediate latent populations shortly after infection.","language":"en"},{"key":"dc.language.iso","value":"eng","language":"en"},{"key":"dc.publisher","value":"University of British Columbia","language":"en"},{"key":"dc.rights","value":"Attribution-NonCommercial-NoDerivatives 4.0 International","language":"*"},{"key":"dc.rights.uri","value":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/","language":"*"},{"key":"dc.title","value":"Investigating the roles of viral and host proteins in regulation of HIV-1 latency","language":"en"},{"key":"dc.type","value":"Text","language":"en"},{"key":"dc.degree.name","value":"Doctor of Philosophy - PhD","language":"en"},{"key":"dc.degree.discipline","value":"Biochemistry and Molecular Biology","language":"en"},{"key":"dc.degree.grantor","value":"University of British Columbia","language":"en"},{"key":"dc.contributor.supervisor","value":"Sadowski, Ivan","language":null},{"key":"dc.date.graduation","value":"2025-05","language":"en"},{"key":"dc.type.text","value":"Thesis\/Dissertation","language":"en"},{"key":"dc.description.affiliation","value":"Medicine, Faculty of","language":"en"},{"key":"dc.description.affiliation","value":"Biochemistry and Molecular Biology, Department of","language":"en"},{"key":"dc.degree.campus","value":"UBCV","language":"en"},{"key":"dc.description.scholarlevel","value":"Graduate","language":"en"}]