Differential Requirement for Cell Fusion and Virion Formation in the Pathogenesis of Varicella-Zoster Virus Infection in Skin and T Cells

Jaya Besser; Minako Ikoma; Konstanze Fabel; Marvin H Sommer; Leigh Zerboni; Charles Grose; Ann M Arvin

doi:10.1128/JVI.78.23.13293-13305.2004

Back

Differential Requirement for Cell Fusion and Virion Formation in the Pathogenesis of Varicella-Zoster Virus Infection in Skin and T Cells

Journal article

Open access

Peer reviewed

Differential Requirement for Cell Fusion and Virion Formation in the Pathogenesis of Varicella-Zoster Virus Infection in Skin and T Cells

Jaya Besser, Minako Ikoma, Konstanze Fabel, Marvin H Sommer, Leigh Zerboni, Charles Grose and Ann M Arvin

Journal of virology, Vol.78(23), pp.13293-13305

12/2004

DOI: 10.1128/JVI.78.23.13293-13305.2004

PMCID: PMC524993

PMID: 15542680

Files and links (1)

url

https://doi.org/10.1128/JVI.78.23.13293-13305.2004View

Published (Version of record) Open Access

Abstract

The protein product of varicella-zoster virus (VZV) ORF47 is a serine/threonine protein kinase and tegument component. Evaluation of two recombinants of the Oka strain, rOka47ΔC, with a C-terminal truncation of ORF47, and rOka47D-N, with a point mutation in the conserved kinase motif, showed that ORF47 kinase function was necessary for optimal VZV replication in human skin xenografts in SCID mice but not in cultured cells. We now demonstrate that rOka47ΔC and rOka47D-N mutants do not infect human T-cell xenografts. Differences in the growth of kinase-defective ORF47 mutants allowed an examination of requirements for VZV pathogenesis in skin and T cells in vivo. Although virion assembly was reduced and no virion transport to cell surfaces was observed, epidermal cell fusion persisted, and VZV polykaryocytes were generated by rOka47ΔC and rOka47D-N in skin. Virion assembly was also impaired in vitro, but VZV-induced cell fusion continued to cause syncytia in cultured cells infected with rOka47ΔC or rOka47D-N. Intracellular trafficking of envelope glycoprotein E and the ORF47 and IE62 proteins, components of the tegument, was aberrant without ORF47 kinase activity. In summary, normal VZV virion assembly appears to require ORF47 kinase function. Cell fusion was induced by ORF47 mutants in skin, and cell-cell spread occurred even though virion formation was deficient. VZV-infected T cells do not undergo cell fusion, and impaired virion assembly by ORF47 mutants was associated with a complete elimination of T-cell infectivity. These observations suggest a differential requirement for cell fusion and virion formation in the pathogenesis of VZV infection in skin and T cells.

Virus-Cell Interactions

Details

Title: Subtitle: Differential Requirement for Cell Fusion and Virion Formation in the Pathogenesis of Varicella-Zoster Virus Infection in Skin and T Cells
Creators: Jaya Besser - Departments of Pediatrics and Microbiology
Minako Ikoma - Departments of Pediatrics and Microbiology
Konstanze Fabel - Departments of Pediatrics and Microbiology
Marvin H Sommer - Departments of Pediatrics and Microbiology
Leigh Zerboni - Departments of Pediatrics and Microbiology
Charles Grose - Departments of Pediatrics and Microbiology
Ann M Arvin - Departments of Pediatrics and Microbiology
Resource Type: Journal article
Publication Details: Journal of virology, Vol.78(23), pp.13293-13305
DOI: 10.1128/JVI.78.23.13293-13305.2004
PMID: 15542680
PMCID: PMC524993
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: American Society for Microbiology
Language: English
Date published: 12/2004
Academic Unit: Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
Record Identifier: 9984093214102771

Metrics

20 Record Views

37 Times Cited - Web of Science