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Journal of Virology, November 2008, p. 11073-11083, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.00205-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Importance of NKT Cells in Resistance to Herpes Simplex Virus, Fate of Virus-Infected Neurons, and Level of Latency in Mice{triangledown} ,{dagger}

Branka Grubor-Bauk,1,2* Jane Louise Arthur,1 and Graham Mayrhofer2*

Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, Adelaide 5000, Australia,1 Discipline of Microbiology and Immunology, School of Molecular and Biomedical Science, University of Adelaide, Adelaide 5005, Australia2

Received 24 January 2008/ Accepted 30 June 2008

Herpes simplex virus type 1 (HSV-1) produces acute mucocutaneous infections, spread to sensory ganglia, and establishment of latency. In addition, neurovirulent strains have potential to invade the central nervous system (CNS), with potentially a lethal outcome. Early activation of defenses at all stages is essential to limit virus load and reduce the risk of neuronal damage, extensive zosteriform skin lesions, and catastrophic spread to the CNS. NKT cells respond rapidly, and we have shown previously that CD1d-deficient mice are compromised in controlling a neuroinvasive isolate of HSV-1. We now compare infection in J{alpha}18 GKO and CD1d GKO mice, allowing direct assessment of the importance of invariant V{alpha}14+ NKT cells and deduction of the role of the CD1d-restricted NKT cells with diverse T-cell receptors. The results indicate that both subsets of NKT cells contribute to virus control both in the afferent phase of infection and in determining the mortality, neuroinvasion, loss of sensory neurons, size of zosteriform, lesions and levels of latency. In particular, both are crucial determinants of clinical outcome, providing protection equivalent to a 1-log dose of virus. These NKT cells can be expected to provide protection at doses of virus that might be encountered naturally.


* Corresponding author. Mailing address for B. Grubor-Bauk: TGR BioSciences Pty Ltd., 31 Dalgleish St., Thebarton 5031, Australia. Phone: (61) 8 83546145. Fax: (61) 8 83546188. E mail: brankagb{at}tgr-biosciences.com.au. Mailing address for G. Mayrhofer: School of Molecular and Biomedical Science, University of Adelaide, Adelaide 5005, Australia. Phone: (61) 8 83034632. Fax: (61) 8 83034362. E-mail: graham.mayrhofer{at}adelaide.edu.au

{triangledown} Published ahead of print on 9 July 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.


Journal of Virology, November 2008, p. 11073-11083, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.00205-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.