Journal of General Virology, Vol 78, 2735-2746, Copyright © 1997 by Society for General Microbiology

ARTICLES

Immune responses to the hepatitis C virus NS4A protein are profoundly influenced by the combination of the viral genotype and the host major histocompatibility complex

ZX Zhang, M Chen, C Hultgren, A Birkett, DR Milich and M Sallberg
Division of Clinical Virology, Huddinge University Hospital, Sweden.

The interaction between the host major histocompatibility complex (MHC) and the genotype of the hepatitis C virus (HCV) was analysed using synthetic full-length non-structural (NS) 4A proteins, residues 1658- 1712, of genotypes 1b, 2b, 3a, 4a and 5a. Human and murine antibodies specific for the five NS4A genotypes analysed focused on residues 1688- 1707. In immunized B10 H-2 congenic mice, the H-2d, H-2f and H-2s haplotypes were good responders to NS4A, irrespective of the viral genotype. In contrast, the H-2k haplotype was a low or non-responder to all NS4A genotypes, except for genotype 2b. Also, H-2f- and H-2s- restricted NS4A genotype 1b-specific T-cells focused on residues 1670- 1679 and 1683-1692, respectively, whereas H-2k-restricted NS4A genotype 2b-specific T-cells focused on the carboxy terminus. Interestingly, H- 2f-restricted genotype 1b-specific T-cells did not cross-react with T- cell site analogues of seven other genotypes, whereas the H-2s- restricted, genotype 1b-specific T-cells cross-reacted with genotypes 1a, 4a and 5a. Thus the combination of viral genotype and host MHC profoundly influences the ability to mount an HCV NS4A-specific immune response.

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