The Herpes Simplex Virus Type 1 BgK L Variant, Unlike the BgO L Variant, Shows a Higher Association with Orolabial Infection than with Infections at Other Sites, Supporting the Variant-Dispersion-Replacement Hypothesis

Abstract

ABSTRACT The identification and geographic distribution of the herpes simplex virus type 1 (HSV-1) BglII restriction fragment length polymorphism (RFLP) variants named BgK L and BgO L in clinical isolates from orolabial and cutaneous sites were described in our previous reports, in which the dispersion and replacement of HSV-1 variants were proposed. The base substitution sites deduced from the BgK L multiple RFLP variations were mapped to the U L 12 (DNase), R L 2 (α0 transactivator), and latency-associated transcript genes in the present study. The results show that the relative frequencies (RFs) of BgK L are significantly higher in orolabial and cutaneous HSV-1 infections than in ocular infections. For the BgO L variant, the opposite was found; i.e., the RF of BgO L was significantly lower in orolabial and cutaneous infections than in ocular infections. No significant differences in the RFs of non-BgK L :non-BgO L isolates were observed. The ratio of the BgK L RF to the BgO L RF was much higher for the orolabial and cutaneous infection groups than for the ocular infection group, whereas the BgK L RF-to-non-BgK L :non-BgO L RF ratios for the former groups were slightly higher than those for the latter group. The higher efficiency of orolabial and cutaneous infections caused by BgK L compared to the efficiency of infections caused by BgO L allows BgK L to spread more efficiently in human populations and to displace BgO L , because the mouth and lips are the most common HSV-1 infection sites in children. The present study supports our HSV-1 dispersion-and-replacement hypothesis and suggests that HSV-1, the latency-reactivation of which allows variants to accumulate in human populations, has evolved under competitive conditions, providing a new perspective on the polymorphism or variation of HSV-1.