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The Antiviral Mechanism of SERINC5 on HIV-1 Infection

dc.contributor.advisorGeorgiev, Ivelin
dc.contributor.advisorAiken, Christopher
dc.creatorFeatherstone, Austin Blake
dc.date.accessioned2020-12-29T15:31:15Z
dc.date.available2020-12-29T15:31:15Z
dc.date.created2020-12
dc.date.issued2020-11-18
dc.date.submittedDecember 2020
dc.identifier.urihttp://hdl.handle.net/1803/16407
dc.description.abstractSERINC5 is a 10-12 transmembrane domain cellular protein that is incorporated into budding HIV-1 particles and reduces HIV-1 infectivity by inhibiting virus-cell fusion. HIV-1 susceptibility to SERINC5 is determined by sequences in the viral Env glycoprotein gp120, and the antiviral effect of SERINC5 is counteracted by the viral accessory protein Nef. While the precise mechanism by which SERINC5 inhibits HIV-1 infectivity is unclear, previous studies have suggested that SERINC5 affects Env conformation. To define the effects of SERINC5 on Env conformation, I quantified the binding of HIV-1 particles to immobilized Env-specific monoclonal antibodies. I observed that SERINC5 reduced the binding of HIV-1 particles bearing a SERINC5-susceptible Env to antibodies that recognize the Env trimer conformation, the V3-loop, a sCD4-induced epitope, and an N-linked glycan. By contrast, SERINC5 did not alter the capture of HIV-1 particles bearing the SERINC5-resistant Env protein. Moreover, the effect of SERINC5 on antibody-dependent virus capture was abrogated by Nef expression. My results indicate that SERINC5 inhibits HIV-1 infectivity by altering the conformation of gp120 on virions and/or physical masking of specific HIV-1 Env epitopes. Defining the specific effects of SERINC5 on the HIV-1 glycoprotein conformation may be useful for designing new antiviral strategies targeting HIV-1 Env.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.subjectSERINC5
dc.subjectHIV-1
dc.subjectrestriction factor
dc.subjectgp120
dc.subjectantiviral mechanism
dc.subjectNef
dc.subjecthost defenses
dc.titleThe Antiviral Mechanism of SERINC5 on HIV-1 Infection
dc.typeThesis
dc.date.updated2020-12-29T15:31:15Z
dc.type.materialtext
thesis.degree.namePhD
thesis.degree.levelDoctoral
thesis.degree.disciplineMicrobe-Host Interactions
thesis.degree.grantorVanderbilt University Graduate School
dc.creator.orcid0000-0002-5039-3549


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