TY  - JOUR
AU  - Sanjuan, R.
AU  - Nebot, M.
AU  - Peris, J. B.
AU  - Alcami, J.
PY  - 2013
DA  - 2013//
TI  - Immune Activation Promotes Evolutionary Conservation of T-Cell Epitopes in HIV-1
T2  - PLoS. Biol.
JO  - Plos Biology
SP  - e1001523 - 10pp
VL  - 11
IS  - 4
PB  - Public Library Science
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.
SN  - 1545-7885
UR  - https://doi.org/10.1371/journal.pbio.1001523
DO  - 10.1371/journal.pbio.1001523
LA  - English
N1  - WOS:000318687800003
ID  - Sanjuan_etal2013
ER  -