Geographical Distribution of the Herpes Simplex Virus Type 1 BgK _L Variant in Japan Suggests Gradual Dispersion of the Virus from Shikoku Island to the Other Islands

Abstract

Restriction endonuclease fragment length polymorphism (RFLP) is useful for the epidemiological study of herpes simplex virus type 1 (HSV-1). We report here the identification of a major BglII RFLP variant of HSV-1, designated BgK L , found in 27.0% of 636 HSV-1 clinical isolates. We have also established its geographic distribution in Japan. BgK L has an unusually large BglII K fragment. SalI cleavage analyses showed that 97% of BgK L variant isolates lack both the SalI C-J and the F-J cleavage sites and have an unusually large SalI D or E fragment, and 91% of the BgK L variants lack both SalI G and H fragments. Furthermore, 96% of BgK L isolates have an unusually small KpnI M fragment. Therefore, BgK L is a marker for these five mutations in most HSV-1 isolates and is a useful HSV-1 RFLP marker. The BgK L variant was found in 59% of HSV-1 isolates from Shikoku Island, 44% of HSV-1 isolates from the Chugoku region of Honshu Island, 31% of HSV-1 isolates from Kyushu Island, 0% of HSV-1 isolates from Okinawa Island, 49% of HSV-1 isolates from Osaka, 27% of HSV-1 isolates from Shiga, 13% of HSV-1 isolates from the Chubu Region, and 9% of HSV-1 isolates from the Tohoku Region of Honshu Island. Differences in the frequency of BgK L between the ShikokuChugoku-Osaka area (49%) and Kyushu, between Kyushu and Okinawa, between the Shikoku-Chugoku-Osaka area and Shiga, and between Shiga and Tohoku are all statistically significant. The BgK L frequency decreases in a geographical gradient suggest that this HSV-1 variant was dispersed from Shikoku to the surrounding regions and then to more distant regions. The BgK L frequency in Tokyo was similar to the nationwide average. These are the first data to suggest a geographic and demographic dispersion pattern of HSV-1. Implications for the epidemiology and diversification of HSV-1 are discussed.DNA restriction endonuclease cleavage patterns and restriction fragment length polymorphism (RFLP) are useful for epidemiological studies of herpes simplex virus type 1 (HSV-1) strains (7,14,15,25,28,29). RFLP profiles have been used to differentiate HSV-1 clinical isolates from epidemiologically unrelated individuals and to determine whether viruses isolated from epidemiologically "connected" individuals are identical (1-3, 5, 9, 12, 13, 16, 18, 19, 23, 26, 28, 36). The data indicate that the genomic DNAs of HSV-1 isolates have accumulated enough base substitutions to allow different isolates to be distinguished. HSV-1 polymorphism also has been observed by differences in the electrophoretic patterns of virion structural proteins of different HSV-1 strains (17,21,28). The lifelong latency and reactivation of HSV-1 infection probably facilitates the accumulation of random mutations and diversification of 37,38). HSV-1 isolates with distinct base substitution mutation(s) at restriction endonuclease cleavage sites are designated RFLP variants in here.It is not known whether an HSV-1 RFLP variant isolated at a certain frequency in a particular population is due to an RFLP variation that aro...

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

“…HSV-1 clinical isolates were obtained from 104 patients with HSV-1 infections of the eyes (herpes simplex keratitis and/or conjunctivitis) and from 40 patients with genital infections (genital HSV). The clinical specimens, the cell inoculation procedures, and the identification and typing of the isolates have been described previously (21). All clinical isolates were obtained before 1986, as were the HSV-1 isolates, which were mostly from the patients with orolabial HSV or skin infections described in our previous report.…”

“…Thus, the BglII K L variation is a surrogate RFLP marker for the five highly associated mutations (21). The geographic distribution of BgK L forms a gradient, suggesting that it dispersed from Shikoku Island to the surrounding regions of Japan (21). Furthermore, the contrasting geographic distribution of BgK L and BgO L variants suggests that the former may have displaced the latter (8).…”

“…Almost all BgK L variant isolates possess the three different SalI RFLP variations designated SaCFJ M, SaE L , and SaGH M , as well as the KpnI RFLP variation KpM S (8,21). Thus, the BglII K L variation is a surrogate RFLP marker for the five highly associated mutations (21).…”

“…HSV-1 is transmitted by close contact between individuals (39). These properties of HSV-1 infection make the association of HSV-1 variants with host populations stable (21,35). HSV-1 is ubiquitous throughout the world (39) and is highly prevalent in Japan (13,44).…”

“…The HSV-1 variant BgK L comprised 27.1% of clinical isolates from patients with orolabial and cutaneous infections in Japan (21,22). Almost all BgK L variant isolates possess the three different SalI RFLP variations designated SaCFJ M, SaE L , and SaGH M , as well as the KpnI RFLP variation KpM S (8,21).…”