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The Cytoplasmic Domain of Varicella-Zoster Virus Glycoprotein H Regulates Syncytia Formation and Skin Pathogenesis


Varicella zoster virus (VZV) infects the human population globally, causing chickenpox in children and shingles in adults. While those afflicted with shingles experience severe pain that might last from weeks to months, the cause is not known. Biopsies of VZV infected skin and specimens of nerve ganglia collected at autopsy from patients with shingles at the time of death contain multi-nucleated cells, indicating that the virus is able to cause fusion between infected cells. Since the destruction of nerve cells that results from this process is likely to contribute to the pain associated with shingles, it is important to understand how the virus causes infected cells to fuse. We find that VZV cell-cell fusion is regulated by the intracellular facing domain of glycoprotein H (gH), a viral protein present on the surface of infected cells. This regulation was dependent upon the physical length of the domain, not a specific sequence. Loss of this regulation increased cell-cell fusion causing the formation of larger multi-nucleated cells that limited the ability of the virus to effectively spread in human skin. Our study provides new insight into how VZV manipulates host cells during infection and controls the spread of the virus in tissues.


Vyšlo v časopise: The Cytoplasmic Domain of Varicella-Zoster Virus Glycoprotein H Regulates Syncytia Formation and Skin Pathogenesis. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004173
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004173

Souhrn

Varicella zoster virus (VZV) infects the human population globally, causing chickenpox in children and shingles in adults. While those afflicted with shingles experience severe pain that might last from weeks to months, the cause is not known. Biopsies of VZV infected skin and specimens of nerve ganglia collected at autopsy from patients with shingles at the time of death contain multi-nucleated cells, indicating that the virus is able to cause fusion between infected cells. Since the destruction of nerve cells that results from this process is likely to contribute to the pain associated with shingles, it is important to understand how the virus causes infected cells to fuse. We find that VZV cell-cell fusion is regulated by the intracellular facing domain of glycoprotein H (gH), a viral protein present on the surface of infected cells. This regulation was dependent upon the physical length of the domain, not a specific sequence. Loss of this regulation increased cell-cell fusion causing the formation of larger multi-nucleated cells that limited the ability of the virus to effectively spread in human skin. Our study provides new insight into how VZV manipulates host cells during infection and controls the spread of the virus in tissues.


Zdroje

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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