QUASI analysis of host immune responses to Gag polyproteins of human immunodeficiency virus type 1 by a systematic bioinformatics approach.
There is a consensus that Gag-specific cytotoxic T lymphocyte (CTL) response plays a key role in the immune control of human immunodeficiency virus type 1 (HIV-1) infection. In this study, we analyzed all currently available gag sequences in the Los Alamos HIV sequence database and identified positive selection (PS) sites likely restricted by the host immune responses. We found that between 23.4% and 47.4% of PS sites were shared by clades A, B, and C of Gag, indicating similar positive selection pressure on Gag in different subtypes of HIV-1. Furthermore, a significant correlation was observed between the combined CTL and antibody responses and PS sites. The Gag regions of free from PS contained 9 CTL epitopes restricted by 11 HLA class I alleles associated with disease progression to acquired immune deficiency syndrome (AIDS). These analyses provide information important for the identification of cross-clade epitopes and development of a global HIV-1 vaccine.
Liang
Binhua
B
Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.
Luo
Ma
M
Ball
T Blake
TB
Jones
Steven J M
SJ
Plummer
Francis A
FA
D016915:AIDS Vaccines / Q000737:chemistry / Q000276:immunology; D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis* / Q000737:chemistry; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000032:analysis / Q000737:chemistry; D008969:Molecular Sequence Data; D020539:Sequence Analysis, Protein / Q000379:methods*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000032:analysis / Q000737:chemistry / Q000276:immunology*
D016915:AIDS Vaccines; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D054301:gag Gene Products, Human Immunodeficiency Virus