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Journal of Clinical Microbiology, July 2007, p. 2183-2190, Vol. 45, No. 7
0095-1137/07/$08.00+0     doi:10.1128/JCM.02472-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Herpes Simplex Virus Type 1 BgKL Variant, Unlike the BgOL Variant, Shows a Higher Association with Orolabial Infection than with Infections at Other Sites, Supporting the Variant-Dispersion-Replacement Hypothesis{triangledown}

Shigeru Ozawa,1,2 Hiroyuki Eda,1,3 Yasuyuki Ishii,1 Fumihiko Ban,1 Toshiyuki Funabashi,4 Seiichiro Hata,5 Kozaburo Hayashi,6 Hiroki Iga,7 Takao Ikushima,8 Hiroaki Ishiko,1 Tomoo Itagaki,9 Rinji Kawana,10 Shunsaku Kobayashi,11 Takeo Ogino,12 Tsuyoshi Sekizawa,13 Yoshikazu Shimomura,14 Hiroshi Shiota,15 Ryoichi Mori,16 Takashi Nakakita,17 Yoshio Numazaki,18 Yoshikatsu Ozaki,19 Shigeru Yamamoto,20 Kamesaburo Yoshino,2,21,{dagger} and Kazuo Yanagi1,22*

Herpesvirus Laboratory, Department of Virology I, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan,1 Yamanashi Institute of Health, Kofu City, Yamanashi Prefecture, Japan,2 Tsukuba University, The Program of Environmental Sciences, Tsukuba City, Ibaraki 305-8572, Japan,3 Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan,4 Osaka University Medical School, Suita City, Osaka Prefecture 565-0871, Japan,5 Kobe Institute of Health, Kobe City, Hyogo Prefecture 650-0046, Japan,6 University of Tokushima School of Dentistry, Tokushima City, Tokushima Prefecture 770-8503, Japan,7 Shizuoka Institute of Environment and Hygiene, Shizuoka, Japan,8 Shimane Prefectural Institute of Public Health and Environment Science, Matsue City, Shimane Prefecture 690-0122, Japan,9 Iwate Medical University School of Medicine, Morioka City, Iwate Prefecture 020-8505, Japan,10 Yamaguchi University School of Medicine, Ube City, Yamaguchi Prefecture 755-8505, Japan,11 Hiroshima City Institute of Public Health, Hiroshima City, Hiroshima Prefecture 733-8650, Japan,12 Tohoku University School of Medicine, Sendai City, Miyagi Prefecture 980-8574, Japan,13 Osaka University School of Medicine, Suita City, Osaka Prefecture 565-0871, Japan,14 University of Tokushima School of Medicine, Tokushima City, Tokushima Prefecture 770-8503, Japan,15 Kyushu University Faculty of Medicine, Fukuoka City, Fukuoka Prefecture 819-0395, Japan,16 Nagoya City Public Health Research Institute, Nagoya City, Aichi Prefecture 467-8615, Japan,17 Sendai National Hospital, Sendai City, Miyagi Prefecture 983-8520, Japan,18 Shiga University of Medical Science, Otsu City, Shiga Prefecture 520-2192, Japan,19 Kurume University School of Medicine, Kurume City, Fukuoka Prefecture 830-0011, Japan,20 Institute of Medical Sciences, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan,21 Institute of Basic Medical Sciences, Tsukuba University, Tsukuba City, Ibaraki 305-8572, Japan,22

Received 11 December 2006/ Returned for modification 18 February 2007/ Accepted 21 April 2007

The identification and geographic distribution of the herpes simplex virus type 1 (HSV-1) BglII restriction fragment length polymorphism (RFLP) variants named BgKL and BgOL 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 BgKL multiple RFLP variations were mapped to the UL12 (DNase), RL2 ({alpha}0 transactivator), and latency-associated transcript genes in the present study. The results show that the relative frequencies (RFs) of BgKL are significantly higher in orolabial and cutaneous HSV-1 infections than in ocular infections. For the BgOL variant, the opposite was found; i.e., the RF of BgOL was significantly lower in orolabial and cutaneous infections than in ocular infections. No significant differences in the RFs of non-BgKL:non-BgOL isolates were observed. The ratio of the BgKL RF to the BgOL RF was much higher for the orolabial and cutaneous infection groups than for the ocular infection group, whereas the BgKL RF-to-non-BgKL:non-BgOL 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 BgKL compared to the efficiency of infections caused by BgOL allows BgKL to spread more efficiently in human populations and to displace BgOL, 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.


* Corresponding author. Present address: AIDS Research Center, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan. Phone: 81-3-5285-1111. Fax: 81-3-5285-1150. E-mail: kyanagi{at}nih.go.jp

{triangledown} Published ahead of print on 2 May 2007.

{dagger} Deceased.


Journal of Clinical Microbiology, July 2007, p. 2183-2190, Vol. 45, No. 7
0095-1137/07/$08.00+0     doi:10.1128/JCM.02472-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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