title: Immunological evasion of immediate-early varicella zoster virus proteins.
abstract: The varicella zoster virus (VZV) causes the childhood disease commonly known as chickenpox and can later in life reactivate as herpes zoster. The adaptive immune system is known to play an important role in suppressing VZV reactivation. A central aspect of this system is the presentation of VZV-derived peptides by the major histocompatibility complex (MHC) proteins. Here, we investigate if key VZV proteins have evolved their amino acid sequence to avoid presentation by MHC based on predictive models of MHC-peptide affinity. This study shows that the immediate-early proteins of all characterized VZV strains are profoundly depleted for high-affinity MHC-I-restricted epitopes. The same depletion can be found in its closest animal analog, the simian varicella virus. Further orthology analysis towards other herpes viruses suggests that the protein amino acid frequency is one of the primary drivers of targeted epitope depletion.
authors.affiliation: Department of Mathematics and Computer Science, University of Antwerp, Antwerp, Belgium. pieter.meysman@uantwerpen.be.|Biomedical Informatics Research Center Antwerp (biomina), University of Antwerp/Antwerp University Hospital, Edegem, Belgium. pieter.meysman@uantwerpen.be.
authors.forename: Pieter
authors.initials: P
authors.lastname: Meysman
authors.affiliation: Institute of Cellular Neurosciences, University of Bonn, Bonn, Germany.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Fedorov
authors.affiliation: Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.
authors.forename: Viggo
authors.initials: V
authors.lastname: Van Tendeloo
authors.affiliation: Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.|Centre for Health Economics Research and Modeling Infectious Diseases (CHERMID), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.|Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, Hasselt, Belgium.
authors.forename: Benson
authors.initials: B
authors.lastname: Ogunjimi
authors.affiliation: Department of Mathematics and Computer Science, University of Antwerp, Antwerp, Belgium.|Biomedical Informatics Research Center Antwerp (biomina), University of Antwerp/Antwerp University Hospital, Edegem, Belgium.
authors.forename: Kris
authors.initials: K
authors.lastname: Laukens
mesh_terms: D000818:Animals; D002644:Chickenpox / Q000276:immunology* / Q000821:virology; D006680:HLA Antigens / Q000276:immunology*; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D057131:Immune Evasion / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D006680:HLA Antigens; D017874:Immediate-Early Proteins; D014759:Viral Envelope Proteins
keywords: HLA association; MHC affinity prediction; Varicella zoster virus; Viral immune evasion