HIV subtype and Nef-mediated immune evasion function correlate with viral reservoir size in early-treated individuals

Author: 
Date created: 
2018-12-07
Identifier: 
etd19985
Keywords: 
HIV
Nef
Viral reservoir
HLA-I downregulation
CD4 downregulation
Viral pathogenesis
Abstract: 

The HIV accessory protein Nef is genetically diverse and modulates key immune evasion and pathogenic functions. Recent early HIV-specific adaptive immune responses were identified as correlates of HIV reservoir size. So, we hypothesized that viral factors facilitating evasion of such responses might also influence reservoir establishment and/or persistence. Plasma HIV RNA-derived nef clones were isolated from 30 acute/early-infected individuals and assessed for their CD4 and HLA-I downregulation function in vitro. We explored the relationships between baseline clinical, immunologic and virologic characteristics, and HIV reservoir size measured 48 weeks following initiation of suppressive cART. Nef-mediated HLA downregulation correlated positively with reservoir size. Furthermore, this function was retained in final multivariable models adjusting for established clinical and immunologic correlates of reservoir size. HIV subtype B infection also emerged as a significant correlate of reservoir size on cART. Results highlight potentially important role of viral factors in modulating viral reservoir establishment and persistence.

Document type: 
Thesis
Rights: 
This thesis may be printed or downloaded for non-commercial research and scholarly purposes. Copyright remains with the author.
File(s): 
Senior supervisor: 
Zabrina Brumme
Department: 
Health Sciences: Faculty of Health Sciences
Thesis type: 
(Thesis) M.Sc.
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