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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
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.
Abstract:
Cytomegaloviruses (CMV) utilize a variety of immunomodulatory strategies to facilitate the establishment of lifelong persistence in their infected hosts. We show that the mouse CMV (MCMV) m155 open reading frame (ORF) is required for the posttranscriptional inhibition of CD40 expression in infected antigen-presenting cells. Consistent with the known importance of CD40-mediated costimulation of T cells, a m155-deficient virus induces enhanced MCMV epitope-specific CD4 T cell responses.
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.
