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Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90M

dc.contributor.authorSmidt, Werner
dc.contributor.emailwerner.smidt@student.up.ac.zaen_US
dc.date.accessioned2013-10-22T09:51:29Z
dc.date.available2013-10-22T09:51:29Z
dc.date.issued2013-08-28
dc.description.abstractThe 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.en_US
dc.description.librarianam2013en_US
dc.description.sponsorshipThis work was supported by the National Research Foundation South Africa under the grant number 71262:2011.en_US
dc.description.urihttp://www.plosone.orgen_US
dc.identifier.citationSmidt W (2013) Potential Elucidation of a Novel CTL Epitope in HIV-1 Protease by the Protease Inhibitor Resistance Mutation L90M. PLoS ONE 8(8): e71888. DOI: 10.1371/journal.pone.0071888en_US
dc.identifier.issn1932-6203
dc.identifier.other10.1371/journal.pone.0071888
dc.identifier.urihttp://hdl.handle.net/2263/32100
dc.language.isoenen_US
dc.publisherPublic Library of Scienceen_US
dc.rights© 2013 Werner Smidt. This is an open-access article distributed under the terms of the Creative Commons Attribution Licenseen_US
dc.subjectHuman immunodeficiency virus (HIV)en_US
dc.subjectAcquired immune deficiency syndrome (AIDS)en_US
dc.subjectAntiretroviral resistance mutationsen_US
dc.subjectElucidation of epitopesen_US
dc.subjectHIV proteaseen_US
dc.titlePotential elucidation of a novel CTL epitope in HIV-1 protease by the protease inhibitor resistance mutation L90Men_US
dc.typeArticleen_US

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