Varicella-zoster virus open reading frame 10 is a virulence determinant in skin cells but not in T cells in vivo

Journal of Virology
Xibing CheAnn M Arvin

Abstract

The open reading frame 10 (ORF10) of varicella-zoster virus (VZV) encodes a tegument protein that enhances transactivation of VZV genes and has homology to herpes simplex virus type 1 (HSV-1) VP16. While VP16 is essential for HSV replication, ORF10 is dispensable for vaccine OKA (VOKA) growth in vitro. We used parent OKA (POKA) cosmids to delete ORF10, producing POKA delta10; point mutations that disrupted the acidic activation domain and the putative motif for binding human cellular factor 1 (HCF-1) in ORF10 protein yielded POKA10-Phe28Ala, POKA10-Phe28Ser, and POKA10-mHCF viruses. Deleting ORF10 or mutating these two functional domains had no effect on VZV replication, immediate-early gene transcription, or virion assembly in vitro. However, deleting ORF10 reduced viral titers and the extent of cutaneous lesions significantly in SCIDhu skin xenografts in vivo compared to POKA. Epidermal cells infected with POKA delta10 had significantly fewer DNA-containing nucleocapsids and complete virions compared to POKA; extensive aggregates of intracytoplasmic viral particles were also observed. Altering the activation or the putative HCF-1 domains of ORF10 protein had no consequences for VZV replication in vivo. Thus, the decreased pat...Continue Reading

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Citations

Jun 8, 2012·Journal of Virology·Anca SelariuHua Zhu
Nov 3, 2006·Journal of Virology·Cristian CillonizWilliam T Ruyechan
Apr 15, 2011·Uirusu·Kyosuke KanaiNaoki Inoue
Feb 11, 2014·Nature Reviews. Microbiology·Leigh ZerboniAnn M Arvin
Jul 26, 2015·Science China. Life Sciences·Wei WangNingShao Xia
Jun 7, 2007·The Journal of Veterinary Medical Science·Yasser M GhanemHideto Fukushi
Jun 30, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ilaria FrassonSara N Richter
Dec 6, 2018·BMC Genomics·István PrazsákZsolt Boldogkői

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