Herpes simplex virus: recurrent and nonrecurrent strains

A study of three Herpes Simplex strains with different frequencies of recurrent disease was done using the New Zealand white rabbit eye model. Each of the three strains, the McKrae strain (high frequency), the E-43 strain (low, frequency), and the CGA-3 (no recurrence) grew well in the rabbit corneal epithelium and produced overt recognizable disease for up to 5 days post-infection, thus minimizing differences in virus reactivation due to a lack of or insufficient ganglionic colonization. Asymptomatic shedding and spontaneous recurrences, as well as iontophoretically induced recurrences, were seen in the E-43 and McKrae strains, but not in the CGA-3-infected animals. The virus strain's optimum temperature was an important aspect of its reactivation process, as shown by the failure of the nonrecurrent CGA-3 to replicate at the host's core temperature (39 degrees C). The fact that these explants yielded infectious virus at 33 degrees C and not at 39 degrees C confirmed that the CGA-3 had colonized the ganglia, and its lack of recurrences or shedding suggests a temperature-dependency relationship. Our observations were further supported by the preferential growth at 39 degrees C of fresh clinical isolates obtained from HSV encephalitis and herpes labialis. Isolates from animals infected with the heterogeneous McKrae were classified as shedders (isolated in the absence of disease) and recurrent (isolated from a recurrent lesion). Both shedders and recurrent isolates were of a homologous nature and retained their phenotype when tested. From this study, we theorize that reactivation and disease may have different regulatory mechanisms. The type of recurrent disease (lesions, asymptomatic shedding, or none) is virus-dependent and frequency of disease may be regulated by host functions.