Herpes keratitis in the absence of anterograde transport of virus from sensory ganglia to the cornea

Katarina Polcicova, Partha Sarathi Biswas, Kaustuv Banerjee, Todd W. Wisner, Barry T. Rouse, David C. Johnson

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Herpes stromal keratitis is an immunopathologic disease in the corneal stroma leading to scarring, opacity, and blindness, and it is an important problem in common corneal surgeries. Paradoxically, virus antigens are largely focused in the epithelial layer of the cornea and not in the stromal layer, and viral antigens are eliminated before stromal inflammation develops. It is not clear what drives inflammation, whether viral antigens are necessary, or how viral antigens reach the stroma. It has been proposed that herpes simplex virus (HSV) travels from the corneal epithelium to sensory ganglia then returns to the stroma to cause disease. However, there is also evidence of HSV DNA and infectious virus persistent in corneas, and HSV can be transmitted to transplant recipients. To determine whether HSV resident in the cornea could cause herpes stromal keratitis, we constructed an HSV US9- mutant that had diminished capacity to move in neuronal axons. US9- HSV replicated and spread normally in the mouse corneal epithelium and to the trigeminal ganglia. However, US9- HSV was unable to return from ganglia to the cornea and failed to cause periocular skin disease, which requires zosteriform spread from neurons. Nevertheless, US9- HSV caused keratitis. Therefore, herpes keratitis can occur without anterograde transport from ganglia to the cornea, probably mediated by virus persistent in the cornea.

Original languageEnglish (US)
Pages (from-to)11462-11467
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number32
StatePublished - Aug 9 2005


  • Neurons
  • Ocular infection
  • Persistent herpes simplex virus
  • Stroma
  • US9 cell-to-cell spread

ASJC Scopus subject areas

  • General


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