Abstract
Varicella-zoster virus (VZV) is a neurotropic alphaherpesvirus that causes chickenpox and shingles. ORF7 is an important virulence determinant of VZV in both human skin and nerve tissues, however, its specific function and involved molecular mechanism in VZV pathogenesis remain largely elusive. Previous yeast two-hybrid studies on intraviral protein-protein interaction network in herpesviruses have revealed that VZV ORF7 may interact with ORF53, which is a virtually unstudied but essential viral protein. The aim of this study is to identify and characterize VZV ORF53, and to investigate its relationship with ORF7. For this purpose, we prepared monoclonal antibodies against ORF53 and, for the first time, characterized it as a ~40 kDa viral protein predominantly localizing to the trans-Golgi network of the infected host cell. Next, we further confirmed the interaction between ORF7 and ORF53 by co-immunoprecipitation and co-localization studies in both plasmid-transfected and VZV-infected cells. Moreover, interestingly, we found that ORF53 lost its trans-Golgi network localization and became dispersed in the cytoplasm of host cells infected with an ORF7-deleted recombinant VZV, and thus ORF7 seems to play a role in normal subcellular localization of ORF53. Collectively, these results suggested that ORF7 and ORF53 may function as a complex during infection, which may be implicated in VZV pathogenesis.
Highlights
Varicella-zoster virus (VZV) is a ubiquitous human-specific alphaherpesvirus that causes chickenpox and VZV ORF7 has a role in normal transGolgi network (TGN) localization of ORF53 been identified to be implicated in VZV skin- and/or neuro-tropism (Zhang et al, 2010; Zerboni et al, 2014; Wang et al, 2015).ORF7 is a VZV tegument protein that is conserved among all alphaherpesviruses (Jiang et al, 2017)
These results indicate that monoclonal antibodies (mAbs) 2G12 detected ORF53, and we used this mAb for further experiments to study relationship between ORF7 and ORF53
Several further studies have demonstrated that deletion of ORF7 does not prevent viral entry, viral replication and viral protein expression as well as retrograde transport of virus particles from axon terminals to somata but substantially affects secondary envelopment and cell-to-cell spread of VZV in differentiated neuronal cells in vitro (Grigoryan et al, 2012; Jiang et al, 2017)
Summary
Varicella-zoster virus (VZV) is a ubiquitous human-specific alphaherpesvirus that causes chickenpox (varicella) and VZV ORF7 has a role in normal TGN localization of ORF53 been identified to be implicated in VZV skin- and/or neuro-tropism (Zhang et al, 2010; Zerboni et al, 2014; Wang et al, 2015).ORF7 is a VZV tegument protein that is conserved among all alphaherpesviruses (Jiang et al, 2017). Varicella-zoster virus (VZV) is a ubiquitous human-specific alphaherpesvirus that causes chickenpox (varicella) and VZV ORF7 has a role in normal TGN localization of ORF53 been identified to be implicated in VZV skin- and/or neuro-tropism (Zhang et al, 2010; Zerboni et al, 2014; Wang et al, 2015). UL51 of herpes simplex virus type 1 (HSV-1), ORF7 is dispensable for VZV growth in cell culture; deletion of ORF7 impairs VZV virulence in ex vivo human skin, and ORF7 is revealed as one of skin-tropic factors of VZV (Zhang et al, 2010). ORF7 has a critical role in the pathogenesis of both skin and nerve infection of VZV, the underlying molecular mechanism have yet to be elucidated. We focused on the properties of ORF53, which is predicted to be a tegument protein consisting of 331 amino acids and is essential for VZV replication (Zhang et al, 2010), and we explored its relationship with ORF7 in both plasmid-transfected and VZV-infected cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
