2026-04-29T04:08:46Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/69322024-09-27T20:47:52Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Sanjuán, Rafael
author
Nebot, Miguel R
author
Peris, Joan B
author
Alcamí, José
funder
Ministerio de Ciencia e Innovación (España)
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Instituto de Salud Carlos III
funder
Red de Investigación Cooperativa en Investigación en Sida (España)
2018-12-21T11:35:29Z
2018-12-21T11:35:29Z
2013-04-02
PLoS Biol. 2013;11(4):e1001523
1545-7885
http://hdl.handle.net/20.500.12105/6932
23565057
10.1371/journal.pbio.1001523
1545-7885
PLoS biology
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 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 TH cell infection is concomitant to epitope recognition (trans-infection). 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 TH epitopes may be counterproductive.
eng
Immune activation promotes evolutionary conservation of T-cell epitopes in HIV-1
journal article
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URL
https://repisalud.isciii.es/bitstreams/2ca2e85c-0a96-4ca0-bc77-9627ba067fbe/download
File
MD5
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application/pdf
ImmuneActivationPromotesEvolutionary_2013.pdf
URL
https://repisalud.isciii.es/bitstreams/55297b2f-7050-4aff-b60c-6c68cd68914b/download
File
MD5
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text/plain
ImmuneActivationPromotesEvolutionary_2013.pdf.txt