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Replication of cowpox virus in macrophages is dependent on the host range factor p28/N1R
Daniel Bourquain1, Livia Schrick2, Bernd Karsten Tischer3
1Centre for Biological Threats and Special Pathogens 1, Robert Koch Institute, Seestraße 10, 13353, Berlin, Germany. bourquaind@rki.de.
Abstract:
Zoonotic orthopoxvirus infections continue to represent a threat to human health. The disease caused by distinct orthopoxviruses differs in terms of symptoms and severity, which may be explained by the unique repertoire of virus factors that modulate the host's immune response and cellular machinery. We report here on the construction of recombinant cowpox viruses (CPXV) which either lack the host range factor p28 completely or express truncated variants of p28. We show that p28 is essential for CPXV replication in macrophages of human or mouse origin and that the C-terminal RING finger domain of p28 is necessary to allow CPXV replication in macrophages.
Insights
Zoonotic orthopoxvirus infections pose a health risk. Cowpox virus (CPXV) replication in macrophages depends on the p28 protein, particularly its C-terminal RING finger domain, for disease severity.
Area of Science:
- Virology
- Immunology
Background:
- Zoonotic orthopoxviruses pose significant threats to public health.
- Disease severity and symptoms vary among orthopoxviruses due to differing viral factors modulating host responses.
- Cowpox virus (CPXV) is a relevant orthopoxvirus in this context.
Purpose of the Study:
- To investigate the role of the host range factor p28 in CPXV replication.
- To determine the essential domains of p28 required for CPXV pathogenesis.
Main Methods:
- Construction of recombinant CPXV lacking p28 or expressing truncated p28 variants.
- Assessment of CPXV replication in macrophages of human and mouse origin.
Main Results:
- The host range factor p28 is essential for CPXV replication in macrophages.
- The C-terminal RING finger domain of p28 is critical for enabling CPXV replication in macrophages.
- Absence or truncation of p28 significantly impairs viral replication in these immune cells.
Conclusions:
- The p28 protein is a key determinant of CPXV host range and replication.
- The C-terminal RING finger domain of p28 plays a vital role in overcoming macrophage-specific antiviral defenses.
- Understanding p28 function provides insights into orthopoxvirus pathogenesis and host-pathogen interactions.
