Abstract Details

Title 'Licensed' Natural Killer (NK) Cells Dominate the Response to Herpes Simplex Virus Type 1 (HSV-1) Infection of the Central Nervous System (CNS)

Topic Infections/AIDS/Prion Disease

Presentation(s) P04 - (-)

Poster/Presentation
Number 002

Objective

Background BACKGROUND: NK cells and CD8+ T-cells mediate resistance to HSV-1 encephalitis in BL/6 mice by restricting the spread of virus in the brain (Kastrukoff et al. 2010). In normal mice, many mature NK cells lack inhibitory receptors for self MHC CL1 and are hyporesponsive in-vitro. They are deemed 'unlicensed.' In contrast, NK cells expressing an inhibitory receptor for self MHC CL 1 are deemed 'licensed.' 'Unlicensed' NK cells were recently reported to dominate the response to the Herpesvirus, mouse cytomegalovirus (MCMV) (Orr et al. 2012).

Design/Methods DESIGN/METHODS: Immune-competent BL/6 mice, mice depleted of NK/NKT cells, mice depleted of CD8+ T-cells, mice depleted of both NK/NKT and CD8+ T-cells, mice treated with anti-asialo GM1 Ab, B.6 CL 1 KO mice (B6.129P2-B2mtm1unc/J), and B6CD1d-/- KO mice treated with anti-CD8 mAb were infected with HSV-1 strain 2 via the oral mucosa. Viral titration studies were performed in the oral mucosa, trigeminal ganglia, brainstem, cerebellum, and cerebrum of 10 mice/day from day 1 to 15 PI.

Results RESULTS: The spread of infectious virus is restricted to the brainstem of immune-competent BL/6 mice, mice depleted of NK/NKT cells, and mice depleted of CD8+ T-cells. In contrast, virus spreads throughout the brain in BL/6 mice depleted of both NK/NKT cells and CD8+ T-cells and in mice treated with anti-asialo GM1 Ab. Surprisingly, infectious virus also spread throughout the brain of B.6 CL 1 KO mice but not B6.CD1d-/- KO mice.

Conclusions CONCLUSIONS: Results from this study support roles for both NK and CD8+ T-cells in restricting the spread of virus in the CNS of BL/6 mice infected with HSV-1 via the oral mucosa. However, the spread of virus throughtout the brain of BL/6 CL 1 KO mice supports a role for 'licensed' NK cells in restricting viral spread.

Authors/Disclosures
Lorne F. Kastrukoff, MD, FAAN (University of British Columbia) PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Douglas L. Arnold, MD, FAAN (Montreal Neurological Institute, McGill Univ)	Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Xfacto communications. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Find therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Idorsia. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kiniksa. Dr. Arnold has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Clario.

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