Structure-Based Design of an RNA-Bindingp-Terphenylene Scaffold that Inhibits HIV-1 Rev Protein Function
Inside Back Cover: Structure-Based Design of an RNA-Bindingp-Terphenylene Scaffold that Inhibits HIV-1 Rev Protein Function (Angew. Chem. Int. Ed. 50/2013)
Immune activation promotes evolutionary conservation of T-cell epitopes in HIV-1.
The immune system should constitute a strong selective pressure promoting viral genetic diversity and evolution. However, HIV shows lower sequence variability at T-cell epitopes than elsewhere in the genome, in contrast with other human RNA viruses. Here, we propose that epitope conservation is a consequence of the particular interactions established between HIV and the immune system. On one hand, epitope recognition triggers an anti-HIV response mediated by cytotoxic T-lymphocytes (CTLs), but on the other hand, activation of CD4(+) helper T lymphocytes (TH cells) promotes HIV replication. Mathematical modeling of these opposite selective forces revealed that selection at the intrapatient l…