Herpes simplex virus type 1 corneal infection results in periocular disease by zosteriform spread

In humans and animal models of herpes simplex virus infection, zosteriform skin lesions have been described which result from anterograde spread of th e virus following invasion of the nervous system. Such routes of viral spre ad have not been fully examined following corneal infection, and the possib le pathologic consequences of such spread are unknown, To investigate this, recombinant viruses expressing reporter genes were generated to quantify a nd correlate gene expression with replication in eyes, trigeminal ganglia, and periocular tissue. Reporter activity peaked in eyes 24 h postinfection and rapidly fell to background levels by 48 h despite the continued presenc e of viral titers. Reporter activity rose in the trigeminal ganglia at 60 h and peaked at 72 h, concomitant with the appearance and persistence of inf ectious virus. Virus was present in the periocular skin from 24 h despite t he lack of significant reporter activity until 84 h postinfection. This det ection of reporter activity was followed by the onset of periocular disease on day 4. Corneal infection with a thymidine kinase-deleted reporter virus displayed a similar profile of reporter activity and viral titer in the ey es, but little or no detectable activity was observed in trigeminal ganglia or periocular tissue. In addition, no periocular disease symptoms were obs erved. These findings demonstrate that viral infection of periocular tissue and subsequent disease development occurs by zosteriform spread from the c ornea to the periocular tissue via the trigeminal ganglion rather than by d irect spread from cornea to the periocular skin. Furthermore, clinical evid ence is discussed suggesting that a similar mode of spreading and disease o ccurs in humans following primary ocular infection.