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RN Lausch, AD Coleman, SJ Molesworth-Kenyon, JE Oakes; Expression of CC Chemokines During Immune Clearance of HSV-1 from the Infected Cornea . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4305.
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Purpose: The CC chemokines MIP-1α, MIP-1ß, and MCP-1 are expressed in virus-infected tissues. We investigated whether these chemokines played a role in immune clearance of HSV-1 from the infected eye. Methods: C57Bl/6 wildtype (WT) and MIP-1α-/- knockout (KO) mice immunized subcutaneously to HSV-1 were challenged 10 days later topically on the scarified cornea with 2x104 PFU HSV-1 strain RE. Eyes were collected 48 hrs later and tissue lysates were assayed for infectious virus by plaque assay and chemokines by ELISA. Results: Two days after virus challenge HSV-1 titers in the eyes of immune WT hosts were consistently 10 to 100-fold lower than that observed in the eyes of immunized KO hosts. Depletion of CD4+ T cells but not CD8+ T cells abrogated immune clearance. Substantial levels of MIP-1α (≷100pg/ml) were detected in immunized WT corneas whereas no MIP-1α was detected in KO hosts, or naïve WT mice. MIP-1ß was some 18-fold higher in immune WT than in naïve WT host and 4-fold higher in immune WT compared to immune KO mice. In contrast, MCP-1 levels were only 2-fold higher versus naïve WT, and not significantly higher than that found in immune KO mice. Conclusion: Our results suggest that MIP-1α is required for efficient HSV-1 clearance from the cornea. MIP-1ß may also be needed whereas MCP-1 appears to be of lesser importance.
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