Author Type

Undergraduate Student

Date of Award

Spring 12-9-2025

Document Type

Thesis

Publication Status

Version of Record

Submission Date

July 2026

College Granting Degree

Harriet L. Wilkes Honors College

Thesis/Dissertation Advisor [Chair]

Susana Valente

Abstract

Per the World Health Organization, approximately 40 million individuals live with the Human Immunodeficiency Virus (HIV) worldwide. Antiretroviral therapy (ART) against HIV limits viral replication but does not eradicate the virus. This is mainly due to the presence of long lived CD4+ T cells harboring transcriptionally silenced integrated proviruses, hidden from the immune system, which are, however, ready to reinitiate a spreading infection as soon as treatment is interrupted. To develop novel strategies to block virus reactivation without treatment, a deep understanding of host factors contributing to HIV transcriptional regulation is needed. Pioneer factors (PFs) are a unique type of transcription factors with the ability to initiate the opening of closed chromatin and can thus bind DNA regions buried deep in nucleosomes to modulate expression of their target genes. The ability of pioneer factors to modulate HIV transcription and latency was investigated. A library of short hairpin RNAs (shRNAs) targeting 25 pioneer factors was designed and screened in the HIV latency model cell line JLat 10.6 to iv identify the impact of the pioneer factors on HIV transcription. Hits were identified and their role in modulating HIV transcription is currently being investigated.

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