Research

Re-evaluating the role of natural killer cells in innate resistance to herpes simplex virus type 1

William P Halford¹ , Jennifer L Maender² and Bryan M Gebhardt³

¹Dept of Veterinary Molecular Biology, Montana State University, Bozeman, MT, USA

²Dept of Dermatology, Baylor College of Medicine, Houston, TX, USA

³Dept of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA USA

author email corresponding author email

Virology Journal 2005, 2:56doi:10.1186/1743-422X-2-56

Published:	17 July 2005

Abstract

Background

Interferon-γ acts to multiply the potency with which innate interferons (α/β) suppress herpes simplex virus type 1 (HSV-1) replication. Recent evidence suggests that this interaction is functionally relevant in host defense against HSV-1. However, it is not clear which WBCs of the innate immune system, if any, limit HSV-1 spread in an IFN-γ dependent manner. The current study was initiated to determine if natural killer (NK) cells provide innate resistance to HSV-1 infection, and if so to determine if this resistance is IFN-γ-dependent.

Results

Lymphocyte-deficient scid or rag2^-/- mice were used to test four predictions of the central hypothesis, and thus determine if innate resistance to HSV-1 is dependent on 1. NK cell cytotoxicity, 2. NK cells, 3. WBCs, or 4. the IFN-activated transcription factor, Stat 1. Loss of NK cell cytotoxic function or depletion of NK cells had no effect on the progression of HSV-1 infection in scid mice. In contrast, viral spread and pathogenesis developed much more rapidly in scid mice depleted of WBCs. Likewise, loss of Stat 1 function profoundly impaired the innate resistance of rag2^-/- mice to HSV-1.

Conclusion

Lymphocyte-deficient mice possess a very tangible innate resistance to HSV-1 infection, but this resistance is not dependent upon NK cells.