In silico discovery of novel cytotoxic T-lymphocyte epitopes in the HIV-1 Pol region in response to antiretroviral resistance mutations

Abstract

The Acquired Immunode ciency Syndrome pandemic continues to have a large social impact. Many advances in the treatment of infection by the causative agent, Human Immunode ciency Virus, have been made in the last three decades. However, this treatment often means a life-long rigorous adherence to treatment and acquisition of resistance mutations to antiretrovirals. Thus far, the e cacy of promising vaccines has been disappointing. In the last decade, interest has grown concerning the interaction between mutations conferring resistance to antiretrovirals and the e ect this has on epitopes recognized by cytotoxic-T-lymphocytes (CTL). Investigating this is a di cult task, owing to both the extreme polymorphism of HIV and the polymorphism of the Human Leukocyte Antigen (HLA) molecules that present peptides to the CTLs. A large amount of HLA-associated CTL escape mutations have been discovered. Together with this, computational approaches in CTL epitope discovery is becoming increasingly accurate. Here, a method of imputing HLA type from patients together with predicting the in uence of anitretroviral mutations was used to discover potential epitopes for the HLA B*15 and B*48 types in the HIV-1 Subtype B pol region.