Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Epstein-Barr virus isolates retain their capacity to evade T cell immunity through BNLF2a despite extensive sequence variation
AU - Horst, Daniëlle
AU - Burrows, Scott R.
AU - Gatherer, Derek
AU - van Wilgenburg, Bonnie
AU - Boer, Ingrid G. J.
AU - Bell, Melissa J.
AU - Ressing, Maaike E.
AU - Wiertz, Emmanuel J. H. J.
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
KW - ATP-Binding Cassette Transporters
KW - Amino Acid Motifs
KW - Amino Acid Sequence
KW - Cell Line
KW - Epstein-Barr Virus Infections
KW - Evolution, Molecular
KW - Genetic Variation
KW - Herpesvirus 4, Human
KW - Histocompatibility Antigens Class I
KW - Humans
KW - Immune Evasion
KW - Molecular Sequence Data
KW - Selection, Genetic
KW - Sequence Alignment
KW - T-Lymphocytes, Cytotoxic
KW - Viral Matrix Proteins
U2 - 10.1128/JVI.05151-11
DO - 10.1128/JVI.05151-11
M3 - Journal article
C2 - 22013037
VL - 86
SP - 572
EP - 577
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 1
ER -