title: Initiating a watch list for Ebola virus antibody escape mutations.
abstract: The 2014 Ebola virus (EBOV) outbreak in West Africa is the largest in recorded history and resulted in over 11,000 deaths. It is essential that strategies for treatment and containment be developed to avoid future epidemics of this magnitude. With the development of vaccines and antibody-based therapies using the envelope glycoprotein (GP) of the 1976 Mayinga strain, one important strategy is to anticipate how the evolution of EBOV might compromise these efforts. In this study we have initiated a watch list of potential antibody escape mutations of EBOV by modeling interactions between GP and the antibody KZ52. The watch list was generated using molecular modeling to estimate stability changes due to mutation. Every possible mutation of GP was considered and the list was generated from those that are predicted to disrupt GP-KZ52 binding but not to disrupt the ability of GP to fold and to form trimers. The resulting watch list contains 34 mutations (one of which has already been seen in humans) at six sites in the GP2 subunit. Should mutations from the watch list appear and spread during an epidemic, it warrants attention as these mutations may reflect an evolutionary response from the virus that could reduce the effectiveness of interventions such as vaccination. However, this watch list is incomplete and emphasizes the need for more experimental structures of EBOV interacting with antibodies in order to expand the watch list to other epitopes. We hope that this work provokes experimental research on evolutionary escape in both Ebola and other viral pathogens.
authors.affiliation: Department of Biological Sciences, University of Idaho, Moscow, ID, United States; Department of Mathematics, University of Idaho, Moscow, ID, United States; Center for Modeling Complex Interactions, University of Idaho, Moscow, ID, United States; Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, ID, United States.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Miller
authors.affiliation: Center for Modeling Complex Interactions, University of Idaho , Moscow, ID , United States.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Johnson
authors.affiliation: Center for Modeling Complex Interactions, University of Idaho, Moscow, ID, United States; Department of Physics, University of Idaho, Moscow, ID, United States.
authors.forename: Aran Z
authors.initials: AZ
authors.lastname: Burke
authors.affiliation: Center for Modeling Complex Interactions, University of Idaho, Moscow, ID, United States; Department of Physics, University of Idaho, Moscow, ID, United States.
authors.forename: Kyle P
authors.initials: KP
authors.lastname: Martin
authors.affiliation: Department of Biological Sciences, University of Idaho, Moscow, ID, United States; Center for Modeling Complex Interactions, University of Idaho, Moscow, ID, United States.
authors.forename: Tanya A
authors.initials: TA
authors.lastname: Miura
authors.affiliation: Department of Biological Sciences, University of Idaho, Moscow, ID, United States; Center for Modeling Complex Interactions, University of Idaho, Moscow, ID, United States; Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, ID, United States.
authors.forename: Holly A
authors.initials: HA
authors.lastname: Wichman
authors.affiliation: Department of Biological Sciences, University of Idaho, Moscow, ID, United States; Center for Modeling Complex Interactions, University of Idaho, Moscow, ID, United States; Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, ID, United States.
authors.forename: Celeste J
authors.initials: CJ
authors.lastname: Brown
authors.affiliation: Center for Modeling Complex Interactions, University of Idaho, Moscow, ID, United States; Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, ID, United States; Department of Physics, University of Idaho, Moscow, ID, United States.
authors.forename: F Marty
authors.initials: FM
authors.lastname: Ytreberg
keywords: Ebola; Escape Mutations; FoldX; Molecular dynamics; Protein stability