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Author  |
Sanjuan, R.; Nebot, M.; Peris, J.B.; Alcami, J. |
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Title |
Immune Activation Promotes Evolutionary Conservation of T-Cell Epitopes in HIV-1 |
Type |
Journal Article |
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Year |
2013 |
Publication |
Plos Biology |
Abbreviated Journal |
PLoS. Biol. |
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Volume |
11 |
Issue |
4 |
Pages |
e1001523 - 10pp |
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Abstract |
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. |
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Address |
Univ Valencia, Inst Cavanilles Biodiversitat & Biol Evolut, Valencia, Spain, Email: rafael.sanjuan@uv.es |
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Publisher |
Public Library Science |
Place of Publication |
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Language |
English |
Summary Language |
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Original Title |
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Series Volume |
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Edition |
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ISSN |
1545-7885 |
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Notes |
WOS:000318687800003 |
Approved |
no |
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Is ISI |
yes |
International Collaboration |
no |
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Call Number |
IFIC @ pastor @ |
Serial |
1446 |
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