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Significance of Tubular Recycling Endosomes in Envelope Glycoprotein Trafficking and Particle Incorporation in HIV-1 Clade B Primary Isolates

Shamshabad, Vishwanutha
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1733842212976571

Abstract Details

2024, MS, University of Cincinnati, Medicine: Immunology.
Human Immunodeficiency virus (HIV-1) was discovered in 1983 from the lymph node sample of a patient at the Pasteur Institute and subsequently was found to be strongly linked to onset of AIDS. HIV-1 and its pathogenesis has been extensively studied now for decades. Many crucial components of the virus such as the viral replication machinery, proteins involved in replication and assembly, fusion of viral and host cells during infection, and many other aspects of the viral lifecycle have been defined. The HIV-1 envelope glycoprotein (Env) is an essential component of the virus, present on the lipid envelope of the virus and involved in cell membrane fusion and entry. An aspect of HIV-1 Env biology that is not well understood is how it interacts with host cell machinery to reach the site of particle assembly on the plasma membrane. This study investigates the involvement of tubular recycling endosome (TRE), a component of the cellular recycling machinery that is involved in transporting internalized cargo, in the trafficking of Env following endocytosis from the plasma membrane. In particular, this study addresses the interactions of primary isolates of HIV-1 Clade B Env with the TRE, using immunofluorescence staining and imaging of TRE markers. This study also focuses on the role of Phosphatidic Acid (PA) in modulating Env interaction with the TRE, and its regulation through phospholipase D (PLD). The effect of disruption of PA production through inhibition of PLD on Env-TRE colocalization was critically assessed using live cell and pulse-chase imaging along with monitoring of TRE markers. The effects of inhibition on infectivity and particle incorporation were evaluated after PLD inhibition. This study confirmed that primary isolate Env associates strongly with the TRE, and that inhibition of TRE formation through PLD inhibition disrupts Env trafficking. Findings here build on those with laboratory isolates of HIV-1 and provide a new potential therapeutic target to inhibit replication of the virus.
Paul Spearman, M.D. (Committee Chair)
Claire Chougnet, Ph.D. (Committee Member)
Ian Lewkowich, Ph.D. (Committee Member)
52 p.
Immunology
Human Immunodeficiency Virus; Envelope Glycoprotein; Tubular Recycling Endosomes; Trafficking; Phospholipase D; Inhibition

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Citations

  • Shamshabad, V. (2024). Significance of Tubular Recycling Endosomes in Envelope Glycoprotein Trafficking and Particle Incorporation in HIV-1 Clade B Primary Isolates [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1733842212976571

    APA Style (7th edition)

  • Shamshabad, Vishwanutha. Significance of Tubular Recycling Endosomes in Envelope Glycoprotein Trafficking and Particle Incorporation in HIV-1 Clade B Primary Isolates. 2024. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1733842212976571.

    MLA Style (8th edition)

  • Shamshabad, Vishwanutha. "Significance of Tubular Recycling Endosomes in Envelope Glycoprotein Trafficking and Particle Incorporation in HIV-1 Clade B Primary Isolates." Master's thesis, University of Cincinnati, 2024. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1733842212976571

    Chicago Manual of Style (17th edition)

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This open access ETD is published by University of Cincinnati and OhioLINK.