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Impact of natural HIV-1 Nef alleles and polymorphisms on SERINC3/5 downregulation

Resource type
Thesis type
(Thesis) M.Sc.
Date created
2019-04-25
Authors/Contributors
Author: Jin, Steven
Abstract
HIV-1 Nef is a multifunctional accessory protein required for efficient viral pathogenesis. It was recently identified that the serine incorporators (SERINC) 3 and 5 are host restriction factors that decrease the infectivity of HIV-1 when incorporated into newly formed virions. However, Nef counteracts these effects by downregulating SERINC from the cell surface. Currently, there lacks a comprehensive study investigating the impact of primary Nef alleles on SERINC downregulation, as most studies to date utilize lab-adapted or reference HIV strains. In this thesis, I characterized and compared SERINC downregulation from >400 Nef alleles isolated from patients with distinct clinical outcomes and subtypes. I found that primary Nef alleles displayed a dynamic range of SERINC downregulation abilities, thus allowing naturally-occurring polymorphisms that modulate this activity to be identified. In addition, I found that Nef alleles isolated from patients with better clinical outcomes had a poorer ability to counteract SERINC, suggesting that variation in this activity may contribute to differences in HIV-1 pathogenesis.
Identifier
etd20242
Copyright statement
Copyright is held by the author.
Permissions
This thesis may be printed or downloaded for non-commercial research and scholarly purposes.
Scholarly level
Supervisor or Senior Supervisor
Thesis advisor: Brockman, Mark
Member of collection
Model
English

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