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Journal of Virology, October 2003, p. 11139-11149, Vol. 77, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.20.11139-11149.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Herpes Simplex Virus Type 2 Induces Rapid Cell Death and Functional Impairment of Murine Dendritic Cells In Vitro

C. A. Jones,1,2,3* M. Fernandez,1 K. Herc,1 L. Bosnjak,4 M. Miranda-Saksena,4 R. A. Boadle,5 and A. Cunningham3,4

Herpesvirus Research Unit,1 Department of Immunology and Infectious Diseases, The Children's Hospital at Westmead,2 Centre for Viral Research,4 Electron Microscope Laboratory,5 Westmead Millennium Institute and ICPMR, Westmead Hospital, Westmead,6 The University of Sydney, Parkville, New South Wales, Australia3

Received 7 January 2003/ Accepted 11 July 2003

Dendritic cells (DC) are critical for stimulation of naive T cells. Little is known about the effect of herpes simplex virus type 2 (HSV-2) infection on DC structure or function or if the observed effects of HSV-1 on human DC are reproduced in murine DC. Here, we demonstrate that by 12 h postinfection, wild-type (wt) HSV-2 (186) abortively infected murine bone marrow-derived DC and induced early cell death compared to UV-inactivated HSV-2 or mock-infected DC. HSV-2-induced loss of DC viability was more rapid than that induced by HSV-1 and was due, in part, to apoptosis, as shown by TEM, caspase-3 activation, and terminal deoxynucleotidyl transferase-mediated dCTP biotin nick end labeling. HSV induced type-specific changes in the murine DC immunophenotype. At 12 h postinfection, wt HSV-2 upregulated DC major histocompatibility complex (MHC) class II expression, and in contrast to UV-inactivated HSV-2, downregulated expression of MHC class I, but it had no effect on surface CD40, CD80, or CD86. Wt HSV-1 (MC-1) induced only CD40 upregulation. More-profound effects on the DC immunophenotype were observed in HSV-2-infected neonatal DC. Wt HSV of either serotype impaired murine DC-induced T-cell alloproliferation and lipopolysaccharide-induced DC interleukin-12 secretion. Thus, there are marked differences in the levels of HSV-induced cytolysis in DC according to the HSV serotype, although HSV-2 displays immunomodulatory effects on the DC immunophenotype and function similar to those of HSV-1.

* Corresponding author. Mailing address: Herpesvirus Research Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Australia. Phone: 61 2 9845 0521. Fax: 61 2 9845 3082. E-mail: cherylj{at}chw.edu.au.

Journal of Virology, October 2003, p. 11139-11149, Vol. 77, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.20.11139-11149.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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