Dataset Information
Sanjuan2013 - Evolution of HIV T-cell epitope, control model
Ontology highlight
ABSTRACT: Control model in which the virus targets a nonimmune cell type C (e.g., hepatocytes, epithelial cells, etc.), instead of T H cells. This model is described in the article: 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 (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. This model is hosted on BioModels Database and identifiedby: MODEL1302180002 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resourcefor published quantitative kinetic models . To the extent possible under law, all copyright and related orneighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public DomainDedication for more information.
ORGANISM(S): Homo sapiens
SUBMITTER: Rafael Sanjuan
PROVIDER: MODEL1302180002 | biostudies-other |
SECONDARY ACCESSION(S): 23565057
REPOSITORIES: biostudies-other
Publications
Immune activation promotes evolutionary conservation of T-cell epitopes in HIV-1.
PLoS biology 20130402 4
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 o ...[more]
