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Updated: Oct 2, 2026
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Characterization of the murine cytomegalovirus 38 kDa m137 gene product
Robert J Visalli1, Jeanette Fairhurst, Subramanian Kothandaraman
1Infectious Diseases Section, Department of Molecular Biology/Virology, Wyeth-Ayerst Research, 401 N. Middletown Road, Pearl River, NY 10965, USA. visallr@war.wyeth.com
Abstract:
Murine cytomegalovirus (MCMV) m137 null mutants, Deltam137A and Deltam137B, were generated by inserting a gpt cassette into a deleted region of the open reading frame. A polyclonal antiserum produced to an Escherichia coli expressed gst-m137 fusion protein was used to show that a 38 kDa polypeptide corresponding to the predicted m137 gene product was present in NIH 3T3 fibroblasts infected with wild-type MCMV but was not detected in Deltam137 infected cells. The protein did not fractionate with infected cell membranes and was not detectable in purified wild-type virions. Plaque size, plaque morphology, and viral yield did not differ significantly between Deltam137 and wild-type MCMV infected 3T3 fibroblasts. The results showed that deletion of the 38 kDa protein did not negatively effect viral growth in 3T3 fibroblasts indicating that the m137 gene product is not essential for replication in these cells. In vivo analysis revealed that two independently isolated m137 mutants showed a significant delay in time until death but ultimately killed 100% of the mice in a SCID mouse model of virulence.
Insights
Murine cytomegalovirus m137 gene deletion mutants showed no impact on viral replication in fibroblasts. However, these mutants exhibited delayed virulence in severe combined immunodeficiency (SCID) mice.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Murine cytomegalovirus (MCMV) is a significant pathogen with complex gene functions.
- The role of the MCMV m137 gene product in viral replication and pathogenesis remains largely uncharacterized.
Purpose of the Study:
- To investigate the function of the MCMV m137 gene product.
- To determine the essentiality of the m137 gene for viral replication in vitro and virulence in vivo.
Main Methods:
- Generation of MCMV m137 null mutants (Deltam137A and Deltam137B) using a gpt cassette insertion.
- Detection of the m137 gene product using polyclonal antiserum against a GST-m137 fusion protein in infected NIH 3T3 fibroblasts.
- Assessment of viral replication by plaque size, plaque morphology, and viral yield assays.
- Evaluation of virulence in a severe combined immunodeficiency (SCID) mouse model.
Main Results:
- The m137 gene product, a 38 kDa polypeptide, was detected in wild-type MCMV infected cells but not in Deltam137 infected cells.
- The m137 protein was not associated with infected cell membranes or purified virions.
- Deletion of the m137 gene did not affect viral growth or yield in 3T3 fibroblasts.
- MCMV m137 mutants showed a significant delay in time to death in SCID mice but ultimately caused 100% mortality.
Conclusions:
- The MCMV m137 gene product is not essential for viral replication in 3T3 fibroblasts.
- The m137 gene plays a role in modulating the virulence of MCMV in a SCID mouse model, potentially affecting the kinetics of pathogenesis.
