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D.J. Carr, W. Kuziel; The Absence of CCR5 Hinders Clearance of HSV–1 in the Cornea of Mice. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2260.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:In response to ocular herpes simplex virus type 1 (HSV–1) infection, the host response includes the local production of cytokines and chemokines including CCL3 (MIP–1α ) and CCL5 (RANTES). These chemokines share a common receptor, CCR5. The present study was undertaken to determine the relevance of CCR5 expression in the host response to ocular HSV–1 infection. Methods:Wild type (C57BL/6, 6–10 weeks old) and CCR5 knockout (CCR5–/–) mice were infected with HSV–1 (McKrae strain, 500 pfu/eye). The mice were assessed for cellular infiltration by slit lamp exam and the use of a dissecting scope. In addition, viral titers were obtained from the anterior segment of the eye (AE), retina, trigeminal ganglia (TG), and brain stem (BS) during the course of acute infection (days 3–7 post infection, p.i.). Flow cytometry was used to assess the T lymphocyte and NK cell populations in the draining lymph nodes of infected mice. Finally, mice were monitored for cumulative survival. Results:Clinical scores of the mice day 5–6 p.i. by slit lamp exam revealed a significant reduction in pathology in the CCR5–/– mice having a mean score of 0.6 +/–0.2 compared to 1.6 +/– 0.3 for the wild type animals (n = 10–12/group). Such results coincided with a reduction in the opacity of the cornea visualized under a dissecting microscrope. Unexpectedly, viral titers were reduced at days 3–5 p.i. in the AE of the CCR5–/– mice. In contrast, the viral titers were elevated in the TG and BS of the CCR5–/– mice 5–7 days p.i. and elevated in the AE day 7 p.i. CCL5 protein levels were increased in the TG and BS of CCR5–/– mice day 7 p.i. as measured by ELISA. However, there was no significant difference in the cumulative survival comparing wild type to CCR5–/– mice. There was a modest increase in T lymphocytes (CD4 and CD8) and a modest decrease in NK cells in the cervical lymph nodes from CCR5–/– mice during acute infection. Conclusions:CCR5 expression facilitates the clearance of HSV–1 following ocular infection. The absence of CCR5 expression on T and NK cells is reflected by a change in trafficking that may impact on viral clearance.
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