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Journal of Virology, May 2001, p. 4878-4888, Vol. 75, No. 10
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.10.4878-4888.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Varicella-Zoster Virus Retains Major Histocompatibility Complex Class I Proteins in the Golgi Compartment of Infected Cells

Allison Abendroth,1 Ines Lin,2 Barry Slobedman,1 Hidde Ploegh,3 and Ann M. Arvin2,*

Centre for Virus Research, Westmead Millennium Institute of Health Research, University of Sydney, Sydney, New South Wales, Australia1; Departments of Pediatrics and Microbiology & Immunology, Stanford University School of Medicine, Stanford, California2; and Department of Pathology, Harvard Medical School, Boston, Massachusetts3

Received 14 July 2000/Accepted 15 February 2001

We sought to examine the effects of varicella-zoster virus (VZV) infection on the expression of major histocompatibility complex class I (MHC I) molecules by human fibroblasts and T lymphocytes. By flow cytometry, VZV infection reduced the cell surface expression of MHC I molecules on fibroblasts significantly, yet the expression of transferrin receptor was not affected. Importantly, when human fetal thymus/liver implants in SCID-hu mice were inoculated with VZV, cell surface MHC I expression was downregulated specifically on VZV-infected human CD3+ T lymphocytes, a prominent target that sustains VZV viremia. The stage in the MHC I assembly process that was disrupted by VZV in fibroblasts was examined in pulse-chase and immunoprecipitation experiments in the presence of endoglycosidase H. MHC I complexes continued to be assembled in VZV-infected cells and were not retained in the endoplasmic reticulum. In contrast, immunofluorescence and confocal microscopy showed that VZV infection resulted in an accumulation of MHC I molecules which colocalized to the Golgi compartment. Inhibition of late viral gene expression by treatment of infected fibroblasts with phosphonoacetic acid did not influence the modulation of MHC I expression, nor did transfection of cells with plasmids expressing immediate early viral proteins. However, cells transfected with a plasmid carrying the early gene ORF66 did result in a significant downregulation of MHC I expression, suggesting that this gene encodes a protein with an immunomodulatory function. Thus, VZV downregulates MHC I expression by impairing the transport of MHC I molecules from the Golgi compartment to the cell surface; this effect may enable the virus to evade CD8+ T-cell immune recognition during VZV pathogenesis, including the critical phase of T-lymphocyte-associated viremia.

* Corresponding author. Mailing address: 300 Pasteur Dr., Rm. G312, Stanford University School of Medicine, Stanford, CA 94305-5208. Phone: (650) 723-5682. Fax: (650) 725-8040. E-mail: aarvin{at}stanford.edu.

Journal of Virology, May 2001, p. 4878-4888, Vol. 75, No. 10
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.10.4878-4888.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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