<p> Current antiretroviral therapy (ART) is highly effective at blocking HIV-1 replication but does not cure the infection due to the persistence of latently-infected cells that are able to undergo cellular proliferation (1). The majority of HIV-1 proviruses that persist during ART are defective. Of the minority that are intact and replication competent, it is not known what fraction are transcriptionally active <i>in vivo</i> versus those that are transcriptionally silent (latently infected). To address this question, I determined the fraction of HIV-1 proviruses in populations of expanded cell clones that express unspliced, cell-associated RNA during ART in one individual. In total, 34 different cell clones carrying either intact or defective proviruses in “Patient 1” from Maldarelli, <i>et al.</i> (1) were assessed. We found that a median of 2.3% of cells within clones harboring replication-competent proviruses contained unspliced HIV-1 RNA. Highest levels of HIV-1 RNA were found in the effector memory T cell subset, including for the replication-competent AMBI-1 clone, which was the source of persistent viremia on ART. The fraction of cells within a clone that contained HIV-1 RNA was not different in clones with replication-competent vs. defective proviruses. However, higher fractions and levels of RNA were found in cells with proviruses containing multiple drug resistance mutations, including those contributing to rebound viremia. These findings suggest that the vast majority of HIV-1 proviruses in persistently-infected cells, including replication-competent proviruses, are transcriptionally silent at any given time. This silence, if maintained over time, may allow infected cells to persist and expand during effective ART.</p><p>
| Identifer | oai:union.ndltd.org:PROQUEST/oai:pqdtoai.proquest.com:13858684 |
| Date | 18 April 2019 |
| Creators | Musick, Andrew Timothy |
| Publisher | Hood College |
| Source Sets | ProQuest.com |
| Language | English |
| Detected Language | English |
| Type | thesis |
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