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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
Karolinska University Hospital Huddinge, Sweden .
Karolinska University Hospital Huddinge, Sweden .
University of Coll Dublin, Ireland .
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
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2012 (English)In: Journal of General Virology, ISSN 0022-1317, E-ISSN 1465-2099, Vol. 93, 1680-1686 p.Article in journal (Refereed) Published
Abstract [en]

It has been well established that immunological escape mutations within the hepatitis C virus genotype (gt) la 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.

Place, publisher, year, edition, pages
Society for General Microbiology , 2012. Vol. 93, 1680-1686 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-81827DOI: 10.1099/vir.0.043745-0ISI: 000307746100007OAI: diva2:556604

Funding Agencies|Swedish Science Council||Swedish Cancer Society||Vinnova||Goljes Memorial Fund||Karolinska Institutet/Sodertorns University||Swedish Research Council|K2012-99X-22017-01-3|Swedish Society of Medicine||Ake Wiberg Foundation||Royal Swedish Academy of Sciences||Ruth and Richard Juhlin Foundation||Karolinska Institutet||Wilhelm and Martina Lundgren Foundation||

Available from: 2012-09-25 Created: 2012-09-24 Last updated: 2012-09-25

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Falkeborn, Tina
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Department of Clinical and Experimental MedicineFaculty of Health Sciences
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