PT Journal
AU Sanjuan, R
   Nebot, M
   Peris, JB
   Alcami, J
TI Immune Activation Promotes Evolutionary Conservation of T-Cell Epitopes in HIV-1
SO Plos Biology
JI PLoS. Biol.
PY 2013
BP e1001523 - 10pp
VL 11
IS 4
DI 10.1371/journal.pbio.1001523
LA English
AB 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 (T-H cells) promotes HIV replication. Mathematical modeling of these opposite selective forces revealed that selection at the intrapatient level can promote either T-cell epitope conservation or escape. We predict greater conservation for epitopes contributing significantly to total immune activation levels (immunodominance), and when T-H cell infection is concomitant to epitope recognition (transinfection). We suggest that HIV-driven immune activation in the lymph nodes during the chronic stage of the disease may offer a favorable scenario for epitope conservation. Our results also support the view that some pathogens draw benefits from the immune response and suggest that vaccination strategies based on conserved T-H epitopes may be counterproductive.
ER