Limited 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.

• It has been well established that immunological escape mutations within the hepatitis C virus genotype (gt) 1a non-structural (NS) 3/4A protease is partly prevented by a reduction of the viral protease fitness. Surprisingly little is known whether similar mutations affect proteases from other genotypes. In the present study, we assessed both the human leukocyte antigen (HLA)-A2-restricted cytotoxic T cell response and gt3a NS3/4A protease fitness. Similar to gt1, the 1073-1081 epitope was also immunodominant within the gt3a-specific HLA-A2-restricted cytotoxic T cell response, despite a homology of only 56% between gt1a and gt3a genes. However, unlike the gt1a NS3/4A protease, all residues within the gt3a 1073-1081 epitope could sequentially be replaced by alanine with a, at least in part, retained protease activity.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Nyckelord

viral fitness

genotype

MEDICINE

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