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School of Pharmacy, University of Connecticut, Storrs, CT 06269
The E3-19K protein from human adenoviruses (Ads) retains class I MHC molecules in the endoplasmic reticulum. As a consequence, the cell surface expression of class I molecules is suppressed, allowing Ads to evade immune surveillance. Using native gel electrophoresis, gel filtration chromatography, and surface plasmon resonance, we show that a soluble form of the Ad type 2 (Ad2) E3-19K protein associates with HLA-A and -B molecules; equilibrium dissociation constants were in the nanomolar range and 
2.5-fold higher affinity for HLA-A (-A*0201, -A*0301, -A*1101, -A*3301, and -Aw*6801) relative to HLA-B (-B*0702 and -B*0801) molecules. Among the alleles of the HLA-A locus examined, HLA-A*3101 associated 15-fold less avidly with soluble E3-19K. Soluble E3-19K interacted only very weakly with HLA-Cw*0304, and no interaction with HLA-Cw*0401 could be detected under identical conditions. Site-directed mutagenesis and flow cytometry demonstrated that MHC residue 56 plays a critical role in the association and endoplasmic reticulum retention of HLA-A molecules by E3-19K. This delineates the spatial environment around residue 56 as a putative E3-19K interaction surface on class I molecules. Overall, our data imply that a link may exist between host genetic factors and the susceptibility of individuals to Ad infections.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This project was supported by National Institutes of Health/National Institute of Allergy and Infectious Diseases Grant AI055717 (to M.B.) and in part by a Predoctoral Fellowship from Boehringer-Ingelheim Pharmaceuticals (to H.L.).
2 H.L. and J.F. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Marlene Bouvier, School of Pharmacy, 69 N. Eagleville Road, U-3092, Storrs, CT 06269. E-mail address: marlene.bouvier{at}uconn.edu
4 Abbreviations used in this paper: Ad, adenovirus; 
2m, 2-microglobulin; E, early region; ER, endoplasmic reticulum; RT, reverse transcriptase; RU, resonance unit; SPR, surface plasmon resonance.
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  G. Roder, L. Geironson, I. Bressendorff, and K. Paulsson Viral Proteins Interfering with Antigen Presentation Target the Major Histocompatibility Complex Class I Peptide-Loading Complex J. Virol., September 1, 2008; 82(17): 8246 - 8252. [Full Text] [PDF]
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