Mathematical modeling of escape of HIV from cytotoxic T lymphocyte responses

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Mathematical modeling of escape of HIV from cytotoxic T lymphocyte responses.

Human immunodeficiency virus (HIV-1 or simply HIV) induces a persistent infection, which in the absence of treatment leads to AIDS and death in almost all infected individuals. HIV infection elicits a vigorous immune response starting about 2-3 weeks post infection that can lower the amount of virus in the body, but which cannot eradicate the virus. How HIV establishes a chronic infection in th...

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Immunodominant Cytotoxic T Lymphocyte Responses in HIV-1 Infection

Despite detailed analysis of the HIV-1–specific cytotoxic T lymphocyte response by various groups, its relation to viral load and viral sequence variation remains controversial. We analyzed HLA-A*0201 restricted cytotoxic T lymphocyte responses in 17 HIV-1–infected individuals with viral loads ranging from , 400 to 221,000 HIV RNA molecules per milliliter of plasma. In 13 out of 17 infected sub...

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Determinants of HIV-1 Mutational Escape From Cytotoxic T Lymphocytes

CD8+ class I-restricted cytotoxic T lymphocytes (CTLs) usually incompletely suppress HIV-1 in vivo, and while analogous partial suppression induces antiretroviral drug-resistance mutations, epitope escape mutations are inconsistently observed. However, escape mutation depends on the net balance of selective pressure and mutational fitness costs, which are poorly understood and difficult to stud...

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Clustered Mutations in HIV-1 Gag Are Consistently Required for Escape from Hla-B27–Restricted Cytotoxic T Lymphocyte Responses

The immune response to HIV-1 in patients who carry human histocompatibility leukocyte antigen (HLA)-B27 is characterized by an immunodominant response to an epitope in p24 gag (amino acids 263-272, KRWIILGLNK). Substitution of lysine (K) or glycine (G) for arginine (R) at HIV-1 gag residue 264 (R264K and R264G) results in epitopes that bind to HLA-B27 poorly. We have detected a R264K mutation i...

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Variable Fitness Impact of HIV-1 Escape Mutations to Cytotoxic T Lymphocyte (CTL) Response

Human lymphocyte antigen (HLA)-restricted CD8(+) cytotoxic T lymphocytes (CTL) target and kill HIV-infected cells expressing cognate viral epitopes. This response selects for escape mutations within CTL epitopes that can diminish viral replication fitness. Here, we assess the fitness impact of escape mutations emerging in seven CTL epitopes in the gp120 Env and p24 Gag coding regions of an indi...

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ژورنال

عنوان ژورنال: Journal of Statistical Mechanics: Theory and Experiment

سال: 2013

ISSN: 1742-5468

DOI: 10.1088/1742-5468/2013/01/p01010