Re-evaluating the role of natural killer cells in innate resistance to herpes simplex virus type 1.
BACKGROUND
Interferon-gamma acts to multiply the potency with which innate interferons (alpha/beta) 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-gamma 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-gamma-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.


CONCLUSIONS
Lymphocyte-deficient mice possess a very tangible innate resistance to HSV-1 infection, but this resistance is not dependent upon NK cells.
Halford
William P
WP
Dept of Veterinary Molecular Biology, Montana State University, Bozeman, MT, USA. halford@montana.edu
Maender
Jennifer L
JL
Gebhardt
Bryan M
BM
D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency; D005260:Female; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID
D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D007371:Interferon-gamma