Cell‐mediated anti‐Gag immunity in pharmacologically induced functional cure of simian AIDS: a 'bottleneck effect'?
IL Shytaj, A Savarino - Journal of medical primatology, 2015 - Wiley Online Library
IL Shytaj, A Savarino
Journal of medical primatology, 2015•Wiley Online LibraryBackground Administration of antiretroviral therapy and two experimental drugs, auranofin
and buthionine sulfoximine (BSO), was previously shown to be followed by drug‐free control
of chronic SIV mac251 infection, decreased immune activation and increased cell‐mediated
anti‐Gag responses. Methods Phylogeny was analysed with Phylogeny. fr. Entropy was
calculated with the specific tool of the HIV Sequence Database. The capsid Gag structure
was computed using SPDBV. The bottleneck effect was simulated through an appropriate …
and buthionine sulfoximine (BSO), was previously shown to be followed by drug‐free control
of chronic SIV mac251 infection, decreased immune activation and increased cell‐mediated
anti‐Gag responses. Methods Phylogeny was analysed with Phylogeny. fr. Entropy was
calculated with the specific tool of the HIV Sequence Database. The capsid Gag structure
was computed using SPDBV. The bottleneck effect was simulated through an appropriate …
Background
Administration of antiretroviral therapy and two experimental drugs, auranofin and buthionine sulfoximine (BSO), was previously shown to be followed by drug‐free control of chronic SIVmac251 infection, decreased immune activation and increased cell‐mediated anti‐Gag responses.
Methods
Phylogeny was analysed with Phylogeny.fr. Entropy was calculated with the specific tool of the HIV Sequence Database. The capsid Gag structure was computed using SPDBV. The bottleneck effect was simulated through an appropriate online tool.
Results
The region of Gag predominantly targeted during control of SIVmac251 infection is highly conserved in primate lentiviruses and plays an important role in capsid architecture. Computer‐aided simulations support the view that the preferential development of immune responses against this region is derived from a ‘bottleneck effect’ after restriction, by auranofin and BSO, of the activated lymphocyte pool.
Conclusions
Restriction of immune activation through auranofin/BSO may result in stochastic selection of cell clones targeting conserved epitopes leading to a functional cure‐like condition.
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