Selecting stable molecular targets for treatment and prevention of AIDS.
The common consideration in approaching protection against HIV, whether by a vaccine or therapeutic, is identification of suitable targets. Among the central criteria for suitability is target stability; i.e. resistance to mutation. In this paper we address the problem of stability, and develop methods for identifying stable targets. The targets that we focus on are structures formed by viral peptides and products of the class I major histocompatibility complex, the target of the immune system. The method mines the large databases of fully sequenced HIV genomes and MHC binding peptides, and takes account of human polymorphism to construct hundreds of subpopulation specific stable targets, each consisting of combinations of 3-5 complexes.
Wang
Yaoyu E
YE
Departments of Bioinformatics, Boston University, Boston, MA 02215, USA. yew@bu.edu
Zhang
Chao
C
Berzofsky
Jay
J
DeLisi
Charles
C
D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control* / Q000628:therapy*; D000465:Algorithms; D000483:Alleles; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D020650:Combinatorial Chemistry Techniques; D019295:Computational Biology; D017124:Conserved Sequence; D016208:Databases, Factual; D019281:Dimerization; D000939:Epitopes; D018390:Gene Targeting; D014644:Genetic Variation; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000627:therapeutic use; D015497:HIV-1 / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry; D011485:Protein Binding; D020539:Sequence Analysis, Protein; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D009842:Oligopeptides; D014764:Viral Proteins; D054303:HIV Reverse Transcriptase