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Jared E. Knickelbein, Anthony J. St. Leger, Robert L. Hendricks; The Role of Natural Killer (NK) Cells in the Control of Acute HSV-1 Infection. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6156. doi: https://doi.org/.
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The role of NK cells in the control of acute HSV-1 infection remains controversial. The purpose of this study was to determine the requirement for NK cells in the control of acute HSV-1 replication within trigeminal ganglia following corneal infection in various strains of mice.
Wild-type (WT), C57BL/6 (B6), perforin (Pfn)-deficient B6, granzyme B (GrB)-deficient B6, WT Balb/c, DBA/2J (Jackson Laboratory; NKG2A-deficient), and DBA/2Ncr (Charles River Laboratory; NKG2A-replete) mice were infected with HSV-1 via the cornea. NK cells were depleted in some groups of mice by intraperitoneal injections of anti-asialo GM1 antibody prior to and following infection. NK cell depletion was confirmed by flow cytometry. Trigeminal ganglia viral titers were determined by standard viral plaque assays of supernatant from tissue homogenates, and statistical differences were determined by either Student’s t-test or ANOVA.
Depletion of NK cells from WT B6 mice resulted in significantly elevated HSV-1 titers within acutely infected trigeminal ganglia compared to non-treated controls. Trigeminal ganglia from Pfn- and GrB-deficient B6 mice contained significantly increased viral titers compared to WT B6 controls. Depletion of NK cells from Balb/c mice did not alter viral titers in acutely infected ganglia compared to non-treated controls. Mice from the DBA/2Ncr colony express the inhibitory NK cell surface receptor NKG2A, while mice from the DBA/2J colony do not. Trigeminal ganglia from acutely infected DBA/2Ncr mice contained significantly higher HSV-1 titers compared to age- and sex-matched DBA/2J mice. However, depletion of NK cells did not alter viral titers in acutely infected ganglia of either DBA/2Ncr or DBA/2J mice.
Lytic granule-mediated NK cell function significantly increases control of acute HSV-1 replication within trigeminal ganglia from highly resistant C57BL/6 mice. Conversely, NK cells are not required for control of acute HSV-1 infection in susceptible Balb/c and DBA/2 strains. Mice from the DBA/2Ncr colony demonstrate greater susceptibility to HSV-1 infection compared to DBA/2J. Genetic differences beyond that responsible for NKG2A expression between the DBA/2 colonies likely account for the significant difference in control of acute HSV-1 ganglionic infection. This study highlights the differences in control of acute HSV-1 infection both between and within mouse strains.
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