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Encephalomyocarditis Virus Entry Unveiled
1Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA cherrys@mail.med.upenn.edu.
Abstract:
Picornaviruses are a widespread group of pathogens that can cause diverse pathologies. Pathogenesis is thought to be driven by the tissue-specific tropisms displayed by these viruses. For example, many picornaviruses can infect the heart and cause viral myocarditis. Encephalomyocarditis virus (EMCV) is a rodent pathogen that causes myocarditis in rodent models and has been used to model this biology. However, the receptor and entry requirements for this virus are poorly understood. L. E. Bazzone, M. King, C. R. MacKay, P. P. Kyawe, et al. (mBio 10:e02734-18, 2019, https://doi.org/10.1128/mBio.02734-18) tackled this problem using CRISPR knockout screening in human cells that are susceptible to EMCV and identified ADAM9 as an essential entry factor for EMCV in mouse and human cells. Since the extracellular domain but not the enzymatic activity or intracellular domain is required for infection, the data suggest that ADAM9 acts as an entry receptor or at an early step in the process, shedding light on the biology of EMCV infection and pathogenesis.
Insights
Encephalomyocarditis virus (EMCV) uses ADAM9 as a crucial factor for cell entry. This discovery enhances understanding of picornavirus infection mechanisms and viral myocarditis.
Area of Science:
- Virology
- Molecular Biology
- Pathogenesis
Background:
- Picornaviruses are diverse pathogens causing various diseases.
- Viral tropism drives picornavirus pathogenesis, with some infecting the heart causing myocarditis.
- Encephalomyocarditis virus (EMCV) models myocarditis but its entry pathway is unclear.
Purpose of the Study:
- To identify the host cell receptor and entry requirements for Encephalomyocarditis virus (EMCV).
- To elucidate the molecular mechanisms underlying EMCV infection and pathogenesis.
Main Methods:
- CRISPR knockout screening was performed in human cells susceptible to EMCV.
- Infection assays were conducted to assess the role of identified factors.
Main Results:
- ADAM9 was identified as an essential entry factor for EMCV in both mouse and human cells.
- The extracellular domain of ADAM9, not its enzymatic activity or intracellular domain, is required for EMCV infection.
- These findings suggest ADAM9 functions as an entry receptor or at an early stage of viral entry.
Conclusions:
- ADAM9 is a critical host factor for EMCV entry into cells.
- Understanding ADAM9's role provides insights into picornavirus tropism and myocarditis.
- This research opens new avenues for studying EMCV pathogenesis and potential therapeutic targets.
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