Open AccessLimited effect on NS3–NS4A protein cleavage after alanine substitutions within the immunodominant HLA-A2-restricted epitope of the hepatitis C virus genotype 3a non-structural 3/4A protease
Author(s) -
Gustaf Ahlén,
L.-W. Antony Chen,
Barbara Roe,
Tina Falkeborn,
Lars Frelin,
William W. Hall,
Matti Sällberg,
Jonas Söderholm
Publication year - 2012
Publication title -
journal of general virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.55
H-Index - 167
eISSN - 1465-2099
pISSN - 0022-1317
DOI - 10.1099/vir.0.043745-0
Subject(s) - ns3 , biology , virology , epitope , protease , genotype , ns2 3 protease , human leukocyte antigen , alanine , virus , hepatitis c virus , antigen , gene , genetics , enzyme , amino acid , biochemistry
It has been well established that immunological escape mutations within the hepatitis C virus genotype (gt) 1a non-structural (NS) 3/4A protease are partly prevented by a reduction in viral protease fitness. Surprisingly little is known about whether similar mutations affect proteases from other genotypes. In the present study, we assessed both the HLA-A2-restricted CTL response and gt3a NS3/4A protease fitness. Similar to gt1, the 1073–1081 epitope was immunodominant within the gt3a-specific HLA-A2-restricted CTL response, despite sequence similarity of only 56 % between the gt1a and gt3a genes. However, unlike the gt1a NS3/4A protease, all residues within the gt3a 1073–1081 epitope could be replaced sequentially by alanine while retaining protease activity, at least in part.