NEUROPILIN-1 IS UPREGULATED BY HTLV-1 bZIP FACTOR AND INHIBITS CELL-TO-CELL TRANSMISSION OF HTLV-1
Author
Kendle, Wesley Lynn
Abstract
Human T-cell Leukemia Virus Type 1 (HTLV-1) is the etiologic agent of devastating diseases, including adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 relies heavily on cell-to-cell transmission as free virions are poorly infectious. Although cell-to-cell transmission is critical for efficient spread of HTLV-1, much is unknown about the impact of extracellular proteins on viral transmission. Infection studies have been predominantly focused on HTLV-1 Transactivator protein (Tax), a viral protein with many roles in infection. HTLV-1 basic leucine zipper factor (HBZ) has recently been implicated infection, but relatively little is known about the role of HBZ in HTLV-1 viral spread. In this study, we found that HBZ upregulates expression of neuropilin-1 (NRP1). Neuropilin-1 is a ubiquitously expressed transmembrane receptor and an HTLV-1 receptor. HBZ is known to interact with a variety of cellular transcription factors, including AP-1 basic leucine zipper (bZIP) factors and cAMP response element binding protein (CBP)/p300 coactivator proteins. Our results indicate that HBZ interacts with certain AP-1 bZIP factors and CBP/p300 at a putative enhancer site downstream of NRP1. We propose a model in which HBZ upregulates NRP1 expression by forming an HBZ/AP-1 bZIP factor heterodimer, which interacts with the putative enhancer site with CBP/p300 coactivators and basal transcription machinery to upregulate expression of NRP1. Intriguingly, we discovered that NRP1 expression on HTLV-1-infected T-cells inhibits cell-to-cell transmission of HTLV-1. Furthermore, NRP1 expression does not alter virion release from infected cells, suggesting that NRP1 doesn’t inhibit transmission through virion retention. We also provide evidence that NRP1 is incorporated into viral particles, resulting in a reduction in virion infectivity. Together, these results indicate that HBZ upregulates expression of NRP1, which reduces infection efficiency.
Subject
Date
2023-07-21
Citation:
APA:
Kendle, Wesley Lynn.
(July 2023).
NEUROPILIN-1 IS UPREGULATED BY HTLV-1 bZIP FACTOR AND INHIBITS CELL-TO-CELL TRANSMISSION OF HTLV-1
(Doctoral Dissertation, East Carolina University). Retrieved from the Scholarship.
(http://hdl.handle.net/10342/13142.)
MLA:
Kendle, Wesley Lynn.
NEUROPILIN-1 IS UPREGULATED BY HTLV-1 bZIP FACTOR AND INHIBITS CELL-TO-CELL TRANSMISSION OF HTLV-1.
Doctoral Dissertation. East Carolina University,
July 2023. The Scholarship.
http://hdl.handle.net/10342/13142.
April 27, 2024.
Chicago:
Kendle, Wesley Lynn,
“NEUROPILIN-1 IS UPREGULATED BY HTLV-1 bZIP FACTOR AND INHIBITS CELL-TO-CELL TRANSMISSION OF HTLV-1”
(Doctoral Dissertation., East Carolina University,
July 2023).
AMA:
Kendle, Wesley Lynn.
NEUROPILIN-1 IS UPREGULATED BY HTLV-1 bZIP FACTOR AND INHIBITS CELL-TO-CELL TRANSMISSION OF HTLV-1
[Doctoral Dissertation]. Greenville, NC: East Carolina University;
July 2023.
Collections
Publisher
East Carolina University