The proteasome inhibitor bortezomib enhances the susceptibility to viral infection

Basler, Michael; Lauer, Christoph; Beck, Ulrike; Gröttrup, Marcus

The proteasome inhibitor bortezomib enhances the susceptibility to viral infection

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Datum

2009

Autor:innen

Basler, Michael

Lauer, Christoph

Beck, Ulrike

Gröttrup, Marcus

Publikationstyp

Zeitschriftenartikel

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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

Zusammenfassung

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.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

BASLER, 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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