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M. Zheng, M. A. Fields, Y. Liu, E. Richter, H. Cathcart, S. S. Atherton; Neutrophil-Mediated Virus Spreading After Herpes Simplex Virus Type 1 (hsv-1) Infection of the Murine Anterior Chamber. Invest. Ophthalmol. Vis. Sci. 2007;48(13):708.
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HSV-1 infection of the murine anterior chamber elicits rapid infiltration of polymorphnuclear cells (PMN). The purpose of these studies was to determine if early infiltrating PMNs play a role in disseminating HSV-1 to the brain and subsequently, to the retina of the contralateral eye.
BALB/c mice were injected intraperitoneally with monoclonal antibody RB6-8C5 (Gr-1) against PMN or control IgG 5h prior to and 1, 3 and 5 days post HSV-1 anterior chamber inoculation (p.i.). At different times p.i., mice were sacrificed; both eyes as well as brain samples containing the SCN were collected for virus recovery or for immunohistochemistry.
Mice treated with Gr-1 ab experienced profound depletion of PMNs in the peripheral blood at day 3 and 5 p.i. compared with the control IgG treated mice by flow cytometry. Milder retinitis (fewer virus-infected cells and fewer infiltrating cells) was observed on day 8 p.i. in the contralateral eye in PMN depleted mice compared with the contralateral eye of control IgG treated mice. More replicating virus was recovered from the contralateral eye of control IgG treated than from the contralateral eye of Gr-1 ab treated mice (4.5 × 103 ± 0.4 × 103 PFU/eye vs. 1.2 × 102 ± 0.21 × 102 PFU/eye). However, in the virus inoculated eye, an extremely high virus titer was observed in Gr-1 ab treated mice compared with control IgG treated mice at day 8 p.i. (1.9 × 105 ± 0.04 × 105 PFU/eye vs. 1.5 × 102 PFU/eye). Immunohistochemistry for HSV-1 and Gr-1 revealed apparent disseminated virus infected cells in the anterior and posterior junctionas well as the posterior segment in the HSV-1 inoculated eye in Gr-1 ab treated mice. However, in the control IgG treated mice; the virus infected cells were aggregated only within the anterior chamber. In Gr-1 treated mice both anterior to posterior virus spread as well as optic nerve to retina patterns of virus spreading were observed. Although a lower titer of virus was observed in the contralateral eye, a higher titer of virus was observed in the SCN of Gr-1 ab treated mice compared with the control IgG treated mice (2.8 × 102 ± 1.0 × 102 PFU/ml vs. 3.3 × 101 ± 5.7 × 101 PFU/ml).
PMN may play an important role both in anterior to posterior spreading of HSV-1 in the injected eye and in the initiation of HSV-1 spreading through the neuronal pathways.
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