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Cutting edge: adenovirus E19 has two mechanisms for affecting class I MHC expression
E M Bennett1, J R Bennink, J W Yewdell
1The G.W. Hooper Foundation, Department of Microbiology and Immunology, University of California, San Francisco 94143, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|May 5, 1999
Summary
Adenovirus E19 protein inhibits antigen presentation by binding TAP and acting as a tapasin inhibitor. This viral immune evasion strategy affects MHC class I expression, even for alleles not directly bound by E19.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Viruses employ immune evasion strategies to evade host defenses.
- Class I Major Histocompatibility Complex (MHC) molecules present viral antigens to cytotoxic T lymphocytes.
- Adenovirus is known to interfere with the Class I MHC pathway.
Purpose of the Study:
- To investigate the dual function of adenovirus E19 protein in immune evasion.
- To elucidate the mechanism by which E19 delays Class I MHC expression.
Main Methods:
- Analysis of adenovirus E19 protein interactions with Class I MHC molecules and TAP complex.
- Utilizing an E19 mutant (DeltaE19) lacking the ER-retention signal.
- Assessing the impact of E19 on Class I MHC maturation and expression.
Main Results:
- Adenovirus E19 binds Class I MHC molecules and retains them in the endoplasmic reticulum (ER).
- E19 also binds the Transporter Associated with Antigen Processing (TAP) complex, inhibiting tapasin activity.
- This tapasin inhibition delays Class I MHC expression, even for alleles weakly bound by E19.
Conclusions:
- Tapasin inhibition is identified as a novel viral immune evasion mechanism.
- Adenovirus utilizes this secondary mechanism to broadly affect antigen presentation.
- E19's dual function enhances viral escape from host immune surveillance.