Sequence-based human leukocyte antigen-B typing of patients infected with Ebola virus in Uganda in 2000: identification of alleles associated with fatal and nonfatal disease outcomes.
The Sudan species of Ebola virus (SEBOV) causes severe, often fatal infection in approximately 50% of infected humans. We sought to determine whether the human leukocyte antigen-B (HLA-B) locus has a role in the outcome of SEBOV disease by typing 77 cases from an outbreak in northern Uganda in 2000-2001. Sequence-based HLA-B typing was performed using leukocytes isolated from 77 patients. Statistical analysis and a predictive discriminant analysis (PDA) were applied to typing data. Epitope prediction software was also applied to SEBOV sequences. Statistically significant associations were found between certain sets of alleles and either fatal or nonfatal disease outcomes. Alleles B*67 and B*15 were associated with fatal outcomes, whereas B*07 and B*14 were associated with nonfatal outcomes. The PDA-derived functions that were produced were 81.8% accurate in classifying patients into their correct outcome group. Several epitopes predicted to bind strongly to HLA-B*07 molecules were identified in the viral polymerase, nucleoprotein, and VP35 protein. HLA-B alleles associated with either fatal or nonfatal outcomes of SEBOV disease were identified and can be used in a predictive model. Studies of HLA-B-restricted epitopes could contribute to characterization of protective host responses and to vaccine development.
Sanchez
Anthony
A
Special Pathogens Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. ans1@cdc.gov
Wagoner
Kent E
KE
Rollin
Pierre E
PE
D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D029043:Ebolavirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*; D005784:Gene Amplification; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology*; D019142:Hemorrhagic Fever, Ebola / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D006650:Histocompatibility Testing; D006801:Humans; D016133:Polymerase Chain Reaction; D016019:Survival Analysis; D016896:Treatment Outcome; D014454:Uganda
D017931:DNA Primers; D018076:DNA, Complementary; D015235:HLA-B Antigens