Pathogenicity of Glycoprotein C-Negative Herpes Simplex Virus Type 1 in Herpetic Keratitis
Recurrent stromal keratitis induced by herpes simplex virus (HSV) type 1 is one of the most important problems in herpetic ocular diseases and has been considered to represent the host’s immunopathologic response to the virus. In the pathogenicity of this disease, glycoprotein C (gC) of HSV-1 has been shown to be essential, because it is reported as immunodominant antigen to induce HSVspecific memory cytotoxic T lymphocytes. gC also functions as a receptor of complement C3b and has been thought to play an important role in natural infection of HSV. Recently, we isolated HSV-1 strains from a patient with recurrent herpetic keratitis. Interestingly, these viruses were shown to be gCnegative by using two different anti-HSV-1, gC-specific monoclonal antibodies. The clinical isolation of the gC-negative HSV strain is an extremely rare event. Molecular analyses of the gC-negative phenotype of these HSV-1 strains revealed that a premature termination of the translation due to a point mutation of the nucleotide occurred in the mid portion of the gC open reading frame and consequently, a truncated, immature gC molecule lacking the transmembrane domain was secreted to the extracellular fluid. We also demonstrated the important role of gC in protection of the virion envelope against complement-mediated damage, by using the gC-positive recombinant viruses derived from one of these clinical isolates. It is thus expected that these rare HSV-1 strains will provide us with valuable information concerning the in vivo functions of gC, especially in ocular disease. The requirement of gC in herpetic stromal keratitis is also discussed.
KeywordsCarbohydrate Codon Recombination Corticosteroid Glutamine
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