The proteasome inhibitor bortezomib enhances the susceptibility to viral infection

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The Journal of Immunology. 2009, 183(10), pp. 6145-6150. ISSN 0022-1767. eISSN 1550-6606. Available under: doi: 10.4049/jimmunol.0901596
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The proteasome, a multicatalytic protease, is responsible for the generation of most MHC class I ligands. Bortezomib, a proteasome inhibitor, is clinically approved for treatment of multiple myeloma and mantle cell myeloma. In the present study, we investigated the effect of bortezomib on viral infection. Infection of bortezomib-treated mice with the lymphocytic choriomeningitis virus (LCMV) led to a decreased cytotoxic T cell response to several LCMV-derived CD8+ T cell epitopes. Bortezomib treatment caused a reduced expansion of CD8+ T lymphocytes and increased viral titers in LCMV-infected mice. Administration of bortezomib during expansion of CD8+ T cells had no influence on the cytotoxic T cell response, suggesting that bortezomib interferes with priming of naive T cells. Indeed, determination of Ag load in spleen 4 days post infection, revealed a reduced presentation of LCMV-derived cytotoxic T cell epitopes on MHC class I molecules. In summary, we show that proteasome inhibition with bortezomib led to an increased susceptibility to viral infection, and demonstrate for the first time, that proteasome inhibitors can alter Ag processing in vivo.

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570 Biowissenschaften, Biologie
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ISO 690BASLER, Michael, Christoph LAUER, Ulrike BECK, Marcus GRÖTTRUP, 2009. The proteasome inhibitor bortezomib enhances the susceptibility to viral infection. In: The Journal of Immunology. 2009, 183(10), pp. 6145-6150. ISSN 0022-1767. eISSN 1550-6606. Available under: doi: 10.4049/jimmunol.0901596
BibTex
@article{Basler2009prote-1130,
  year={2009},
  doi={10.4049/jimmunol.0901596},
  title={The proteasome inhibitor bortezomib enhances the susceptibility to viral infection},
  number={10},
  volume={183},
  issn={0022-1767},
  journal={The Journal of Immunology},
  pages={6145--6150},
  author={Basler, Michael and Lauer, Christoph and Beck, Ulrike and Gröttrup, Marcus}
}
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    <dcterms:abstract xml:lang="eng">The proteasome, a multicatalytic protease, is responsible for the generation of most MHC class I ligands. Bortezomib, a proteasome inhibitor, is clinically approved for treatment of multiple myeloma and mantle cell myeloma. In the present study, we investigated the effect of bortezomib on viral infection. Infection of bortezomib-treated mice with the lymphocytic choriomeningitis virus (LCMV) led to a decreased cytotoxic T cell response to several LCMV-derived CD8+ T cell epitopes. Bortezomib treatment caused a reduced expansion of CD8+  T lymphocytes and increased viral titers in LCMV-infected mice. Administration of bortezomib during expansion of CD8+  T cells had no influence on the cytotoxic T cell response, suggesting that bortezomib interferes with priming of naive T cells. Indeed, determination of Ag load in spleen 4 days post infection, revealed a reduced presentation of LCMV-derived cytotoxic T cell epitopes on MHC class I molecules. In summary, we show that proteasome inhibition with bortezomib led to an increased susceptibility to viral infection, and demonstrate for the first time, that proteasome inhibitors can alter Ag processing in vivo.</dcterms:abstract>
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