Comparing effects of BK virus agnoprotein and herpes simplex-1 ICP47 on MHC-I and MHC-II expression

Cioni, Michela and Mittelholzer, Christian and Wernli, Marion and Hirsch, Hans H.. (2013) Comparing effects of BK virus agnoprotein and herpes simplex-1 ICP47 on MHC-I and MHC-II expression. Clinical & developmental immunology, 2013, 626823.

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Official URL: http://edoc.unibas.ch/dok/A6338475

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BACKGROUND: Among human polyomaviruses, only BK virus (BKV) and JC virus (JCV) encode an agnoprotein upstream of VP1 on the viral late transcript. BKV agnoprotein is abundantly expressed late in the viral life cycle, but specific cellular and humoral immune responses are low or absent. We hypothesized that agnoprotein might contribute to BKV immune evasion by downregulating HLA expression, similar to Herpes simplex virus-1 ICP47. METHODS: UTA-6 or primary human renal proximal tubular epithelial cells (RPTEC) were co-transfected with plasmids constitutively expressing agnoprotein, or ICP47, and enhanced green-fluorescent protein (EGFP). EGFP-gated cells were analyzed for HLA-ABC and HLA-DR expression by flow cytometry. HLA-ABC and HLA-DR expression was also analyzed on UTA-6 bearing tetracycline-regulated agnoprotein or ICP47. Effects of agnoprotein on viral peptide-dependent T-cell killing were investigated using (51)Cr release. RESULTS: ICP47 downregulated HLA-ABC without affecting HLA-DR, whereas agnoprotein did not affect HLA-ABC or HLA-DR expression. Interferon- gamma treatment increased HLA-ABC in a dose-dependent manner, which was antagonized by ICP47, but not by agnoprotein. In UTA-6 cells, agnoprotein expression did neither impair HLA-ABC or -DR expression nor peptide-specific killing impaired by HLA-matched T-cells. CONCLUSION: Unlike the HSV-1 ICP47, BKV agnoprotein does not contribute to viral immune evasion by down-regulating HLA-ABC, or interfere with HLA-DR expression or peptide-dependent T-cell cytotoxicity.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Transplantation Virology (Hirsch)
UniBasel Contributors:Hirsch, Hans H.
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:04 Sep 2015 14:32
Deposited On:10 Apr 2015 09:12

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