Comprehensive analysis of varicella-zoster virus proteins using a new monoclonal antibody collection

Varicella-zoster virus (VZV) is the etiological agent of chickenpox and shingles. Due to the virus's restricted host and cell typetropism and the lack of tools for VZV proteomics, it is one of the least-characterized human herpesviruses. We generated 251monoclonal antibodies (MAbs) against 59 of the 71 (83%) currently known unique VZV proteins to characterize VZV proteinexpression in vitro and in situ. Using this new set of MAbs, 44 viral proteins were detected by Western blotting (WB) and indirectimmunofluorescence (IF); 13 were detected by WB only, and 2 were detected by IF only. A large proportion of viral proteinswas analyzed for the first time in the context of virus infection. Our study revealed the subcellular localization of 46 proteins, 14of which were analyzed in detail by confocal microscopy. Seven viral proteins were analyzed in time course experiments andshowed a cascade-like temporal gene expression pattern similar to those of other herpesviruses. Furthermore, selected MAbstested positive on human skin lesions by using immunohistochemistry, demonstrating the wide applicability of the MAb collection.Finally, a significant portion of the VZV-specific antibodies reacted with orthologs of simian varicella virus (SVV), thusenabling the systematic analysis of varicella in a nonhuman primate model system. In summary, this study provides insight intothe potential function of numerous VZV proteins and novel tools to systematically study VZV and SVV pathogenesis.

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