Replication of cowpox virus in macrophages is dependent on the host range factor p28/N1R

Daniel Bourquain,Bernd Karsten Tischer,Lars Schaade,Andreas Nitsche,Klaus Osterrieder,Livia Schrick

doi:10.1186/s12985-021-01640-x

Daniel Bourquain, Bernd Karsten Tischer + Show 4 more

Open Access

https://doi.org/10.1186/s12985-021-01640-x

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Journal: Virology journal	Publication Date: Aug 23, 2021
Citations: 3	License type: open-access

Affiliation: Robert Koch Institute

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.

Highlights

Virions of members within the family Poxviridae are large and complex, contain a double-stranded DNA genome of 130–375 kbp, and virus replication takes place in the cytosol [1]
We show that cowpox viruses (CPXV) lacking a functional p28 replicated less efficiently in macrophages of human or mouse origin, indicating that CPXV—like ectromelia virus (ECTV)—is dependent on p28 to productively infect cells of the macrophage lineage
Given the importance of macrophages in containing systemic poxvirus dissemination [19], p28 may be important for CPXV virulence in vivo

Summary

Introduction

Virions of members within the family Poxviridae are large and complex, contain a double-stranded DNA genome of 130–375 kbp, and virus replication takes place in the cytosol [1]. Especially the genus Orthopoxvirus (OPV) contains several important pathogens, and endemic cowpox viruses (CPXV) are the most common cause of zoonotic OPV infections in Europe and parts of northern and central Asia today [2, 3]. The p28 protein of poxviruses belongs to the KilA-N/ RING domain-containing p28/N1R protein family [6,7,8]. The p28 protein was first described as a virulence factor of ectromelia virus (ECTV) [9].

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Conclusion