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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Measles Virus Matrix Protein Inhibits Host Cell Transcription
Xuelian Yu1, Shadi Shahriari2, Hong-Mei Li3
1Section of Epidemiology & Statistics, Department of Public Health, Xinjiang Medical University, 393 XinYi Road, Urumqi, PR China.
Abstract:
Measles virus (MeV) is a highly contagious virus that still causes annual epidemics in developing countries despite the availability of a safe and effective vaccine. Additionally, importation from endemic countries causes frequent outbreaks in countries where it has been eliminated. The M protein of MeV plays a key role in virus assembly and cytopathogenesis; interestingly, M is localised in nucleus, cytoplasm and membranes of infected cells. We have used transient expression of M in transfected cells and in-cell transcription assays to show that only some MeV M localizes to the nucleus, in addition to cell membranes and the cytoplasm as previously described, and can inhibit cellular transcription via binding to nuclear factors. Additionally, MeV M was able to inhibit in vitro transcription in a dose-dependent manner. Importantly, a proportion of M is also localized to nucleus of MeV infected cells at early times in infection, correlating with inhibition of cellular transcription. Our data show, for the first time, that MeV M may play a role early in infection by inhibiting host cell transcription.
Insights
Measles virus M protein inhibits host cell transcription early in infection. This finding reveals a new mechanism for measles virus pathogenesis and potential therapeutic targets.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Measles virus (MeV) remains a global health concern, causing epidemics and outbreaks.
- The MeV M protein is crucial for virus assembly and pathogenesis.
- M protein localization includes nucleus, cytoplasm, and cell membranes.
Purpose of the Study:
- To investigate the nuclear localization and function of MeV M protein.
- To determine if MeV M protein inhibits host cell transcription.
- To elucidate the role of M protein in early MeV infection.
Main Methods:
- Transient expression of M protein in transfected cells.
- In-cell transcription assays.
- In vitro transcription inhibition assays.
Main Results:
- MeV M protein localizes to the nucleus in a subset of transfected cells.
- Nuclear M protein inhibits cellular transcription by binding nuclear factors.
- MeV M protein inhibits in vitro transcription dose-dependently.
- M protein is found in the nucleus of infected cells early in infection, correlating with transcriptional inhibition.
Conclusions:
- MeV M protein can inhibit host cell transcription.
- Nuclear localization of M protein plays a role in early MeV infection.
- This M protein function offers a novel target for antiviral strategies against measles.
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