Abstract:
The combination of host immune responses and use of antiretrovirals facilitate partial control of human immunodeficiency
virus type 1 (HIV-1) infection and result in delayed progression to Acquired Immunodeficiency Syndrome (AIDS). Both
treatment and host immunity impose selection pressures on the highly mutable HIV-1 genome resulting in antiretroviral
resistance and immune escape. Researchers have shown that antiretroviral resistance mutations can shape cytotoxic Tlymphocyte
immunity by altering the epitope repertoire of HIV infected cells. Here it was discovered that an important
antiretroviral resistance mutation, L90M in HIV protease, occurs at lower frequencies in hosts that harbor the B*15, B*48 or
A*32 human leukocyte antigen subtypes. A likely reason is the elucidation of novel epitopes by L90M. NetMHCPan
predictions reveal increased affinity of the peptide spanning the HIV protease region, PR 89–97 and PR 90–99 to HLA-B*15/
B*48 and HLA-A*32 respectively due to the L90M substitution. The higher affinity could increase the chance of the epitope
being presented and recognized by Cytotoxic T-lymphocytes and perhaps provide additional immunological pressures in
the presence of antiretroviral attenuating mutations. This evidence supports the notion that knowledge of HLA allotypes in
HIV infected individuals could augment antiretroviral treatment by the elucidation of epitopes due to antiretroviral
resistance mutations in HIV protease.
