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MHC I-dependent antigen presentation is inhibited by poliovirus protein 3A

S B Deitz1, D A Dodd, S Cooper

  • 1Departments of Microbiology and Immunology, and Structural Biology, Stanford University, School of Medicine, Stanford, CA 94305, USA.

Proceedings of the National Academy of Sciences of the United States of America
|November 30, 2000
PubMed

Insights

Poliovirus protein 3A hinders hepatitis C virus antigen presentation by inhibiting protein secretion, aiding viral immune evasion. This mechanism helps nonenveloped viruses like poliovirus avoid cellular immune detection.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Hepatitis C virus (HCV) antigens are presented to cytotoxic T cells for immune surveillance.
  • Viruses have evolved mechanisms to evade host immune responses.

Purpose of the Study:

  • To investigate how poliovirus 3A protein and poliovirus infection affect the presentation of HCV antigens in chimpanzee cells.
  • To determine if poliovirus 3A protein's inhibition of protein secretion is involved in immune evasion.

Main Methods:

  • Expression of poliovirus 3A protein and poliovirus infection in cultured chimpanzee cells.
  • Standard 51Cr-release assays to measure lysis by HCV-specific cytotoxic T cells.
  • Assessment of cytotoxic T cell activation to determine antigen presentation levels.
  • Utilizing a mutant 3A protein that does not inhibit protein secretion.

Main Results:

  • Poliovirus 3A protein expression inhibited protein secretion and protected cells from cytotoxic T cell lysis.
  • Poliovirus infection decreased cytotoxic T cell activation, indicating impaired antigen presentation.
  • A mutation in 3A that abolished secretion inhibition also abolished the effect on antigen presentation.
  • Inhibition of cellular secretion by poliovirus significantly reduces cell surface antigen presentation.

Conclusions:

  • Poliovirus 3A protein-mediated inhibition of protein secretion is a key mechanism for evading cytotoxic T cell responses.
  • Impaired antigen presentation on the cell surface is a consequence of poliovirus-induced secretion inhibition.
  • This mechanism likely represents a general strategy for immune evasion by nonenveloped viruses that do not rely on the host's protein secretory pathway.

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