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J Virol, May 1998, p. 3705-3710, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Absence of Macrophage Inflammatory Protein-1alpha Prevents the Development of Blinding Herpes Stromal Keratitis

Terrence M. Tumpey,1,dagger Hao Cheng,1 Donald N. Cook,2 Oliver Smithies,3 John E. Oakes,1 and Robert N. Lausch1,*

Department of Microbiology and Immunology, University of South Alabama, Mobile, Alabama 366881; Schering-Plough Research Institute, Kenilworth, New Jersey 070332; and Department of Pathology, University of North Carolina, Chapel Hill, North Carolina 275993

Received 21 November 1997/Accepted 2 February 1998

Prior studies in our laboratory have suggested that the CC chemokine macrophage inflammatory protein-1alpha (MIP-1alpha ) may be an important mediator in the blinding ocular inflammation which develops following herpes simplex virus type 1 (HSV-1) infection of the murine cornea. To directly test this hypothesis, MIP-1alpha -deficient (-/-) mice and their wild-type (+/+) counterparts were infected topically on the scarified cornea with 2.5 × 105 PFU of HSV-1 strain RE and subsequently graded for corneal opacity. Four weeks postinfection (p.i.), the mean corneal opacity score of -/- mice was 1.1 ± 0.3 while that of the +/+ mice was 3.7 ± 0.5. No detectable infiltrating CD4+ T cells were seen histologically at 14 or 21 days p.i. in -/- animals, whereas the mean CD4+ T-cell count per field (36 fields counted) in +/+ hosts was 26 ± 2 (P < 0.001). In addition, neutrophil counts in the -/- mouse corneas were reduced by >80% in comparison to the wild-type controls. At 2 weeks p.i., no interleukin-2 or gamma interferon could be detected in six of seven -/- mice, whereas both T-cell cytokines were readily demonstrable in +/+ mouse corneas. Also, MIP-2 and monocyte chemoattractant protein-1 protein levels were significantly lower in MIP-1alpha -/- mouse corneas than in +/+ host corneas, suggesting that MIP-1alpha directly, or more likely indirectly, influences the expression of other chemokines. Interestingly, despite the paucity of infiltrating cells, HSV-1 clearance from the eyes of -/- mice was not significantly different from that observed in +/+ hosts. We conclude that MIP-1alpha is not needed to control virus growth in the cornea but is essential for the development of severe stromal keratitis.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of South Alabama, Mobile, AL 36688. Phone: (334) 460-6250. Fax: (334) 460-7931. E-mail: lausch{at}sungcg.usouthal.edu.

dagger Present address: Centers for Disease Control and Prevention, Influenza Branch, Atlanta, GA 30333.

J Virol, May 1998, p. 3705-3710, Vol. 72, No. 5
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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