The mouse cytomegalovirus glycoprotein m155 inhibits CD40 expression and restricts CD4 T cell responses

Andrea I Loewendorf1, Lars Steinbrueck, Christoph Peter

  • 1Division of Immune Regulation, The La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.

Journal of Virology
|March 18, 2011
PubMed

Insights

Mouse cytomegalovirus (MCMV) uses the m155 gene to suppress CD40 on antigen-presenting cells. A virus lacking m155 boosts T cell responses, aiding the immune system in fighting MCMV infection.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Cytomegaloviruses (CMV) establish lifelong infections through immune evasion.
  • Antigen-presenting cells (APCs) play a crucial role in initiating adaptive immune responses.
  • CD40 costimulation is vital for effective T cell activation.

Purpose of the Study:

  • To investigate the role of mouse cytomegalovirus (MCMV) m155 open reading frame (ORF) in immune modulation.
  • To determine the impact of m155 on CD40 expression in infected cells.
  • To assess the effect of m155 deficiency on T cell responses during MCMV infection.

Main Methods:

  • Utilized a m155-deficient MCMV mutant.
  • Analyzed CD40 expression on infected antigen-presenting cells.
  • Quantified MCMV epitope-specific CD4 T cell responses.

Main Results:

  • The MCMV m155 ORF is essential for the posttranscriptional suppression of CD40 expression in infected APCs.
  • Mice infected with a m155-deficient MCMV exhibited heightened CD4 T cell responses specific to MCMV epitopes.
  • This suggests m155 normally acts to dampen T cell immunity.

Conclusions:

  • MCMV m155 ORF is a key viral factor that inhibits CD40 expression on infected cells.
  • Disabling m155 enhances CD4 T cell immunity against MCMV.
  • This finding provides insight into CMV immune evasion strategies and potential therapeutic targets.