Epstein-Barr virus isolates retain their capacity to evade T cell immunity through BNLF2a despite extensive sequence variation.
The Epstein-Barr virus (EBV)-encoded immune evasion protein BNLF2a inhibits the transporter associated with antigen processing (TAP), thereby downregulating HLA class I expression at the cell surface. As a consequence, recognition of EBV-infected cells by cytotoxic T cells is impaired. Here, we show that sequence polymorphism of the BNLF2a protein is observed with natural EBV isolates, with evidence for positive selection. Despite these mutations, the BNLF2a variants efficiently reduce cell surface HLA class I levels. This conservation of BNLF2a function during evolution of EBV implies an important role for the viral TAP inhibitor in preventing T cell recognition during viral infection.
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Daniëlle
D
Horst
Scott R
SR
Burrows
Derek
D
Gatherer
Bonnie
B
van Wilgenburg
Melissa J
MJ
Bell
Ingrid G J
IG
Boer
Maaike E
ME
Ressing
Emmanuel J H J
EJ
Wiertz
D018528:ATP-Binding Cassette Transporters / Q000276:immunology; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002460:Cell Line; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000821:virology; D019143:Evolution, Molecular; D014644:Genetic Variation; D004854:Herpesvirus 4, Human / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D008969:Molecular Sequence Data; D012641:Selection, Genetic; D016415:Sequence Alignment; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*
D018528:ATP-Binding Cassette Transporters; C539239:BNLF21 protein, human herpesvirus 4; D015395:Histocompatibility Antigens Class I; D014763:Viral Matrix Proteins; C477327:transporter associated with antigen processing (TAP)