Calcineurin phosphatase activity regulates Varicella-Zoster Virus induced cell-cell fusion.

PLoS Pathogens
Momei ZhouStefan Oliver

Abstract

Cell-cell fusion (abbreviated as cell fusion) is a characteristic pathology of medically important viruses, including varicella-zoster virus (VZV), the causative agent of chickenpox and shingles. Cell fusion is mediated by a complex of VZV glycoproteins, gB and gH-gL, and must be tightly regulated to enable skin pathogenesis based on studies with gB and gH hyperfusogenic VZV mutants. Although the function of gB and gH-gL in the regulation of cell fusion has been explored, whether host factors are directly involved in this regulation process is unknown. Here, we discovered host factors that modulated VZV gB/gH-gL mediated cell fusion via high-throughput screening of bioactive compounds with known cellular targets. Two structurally related non-antibiotic macrolides, tacrolimus and pimecrolimus, both significantly increased VZV gB/gH-gL mediated cell fusion. These compounds form a drug-protein complex with FKBP1A, which binds to calcineurin and specifically inhibits calcineurin phosphatase activity. Inhibition of calcineurin phosphatase activity also enhanced both herpes simplex virus-1 fusion complex and syncytin-1 mediated cell fusion, indicating a broad role of calcineurin in modulating this process. To characterize the role of...Continue Reading

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Citations

Dec 2, 2020·Biochemical Society Transactions·Stefan L OliverAnn M Arvin

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Methods Mentioned

BETA
xenografts
Fluorescence
nuclear translocation
fluorescence microscopy
nuclear
Confocal microscopy
transfection
PCR
pulldown
flow cytometry

Software Mentioned

MatLab
Uniphosphoprotein - finder
Clustal
Byonic
FFmpeg Developers
alignment
FFmpeg
ImageJ
TreeStar
Clustal Omega

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