Comparison of the Complete DNA Sequences of the Oka Varicella Vaccine and Its Parental Virus

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http://jvi.asm.org/cgi/content/abstract/76/22/11447

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Comparison of the Complete DNA Sequences of the Oka Varicella Vaccine and Its Parental Virus

Yasuyuki Gomi,¹ Hiroki Sunamachi,¹ Yasuko Mori,² Kazuhiro Nagaike,^1,2 Michiaki Takahashi,³ and Koichi Yamanishi^2*

Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa,¹ The Research Foundation for Microbial Diseases of Osaka University,³ Department of Microbiology, Osaka University Medical School, Suita, Osaka, Japan²

Received 25 March 2002/ Accepted 14 August 2002

The DNA sequences of the Oka varicella vaccine virus (V-Oka)and its parental virus (P-Oka) were completed. Comparison of the sequences revealed 42 base substitutions, which led to 20amino acid conversions and length differences in tandem repeatregions (R1, R3, and R4) and in an origin of DNA replication.Amino acid substitutions existed in open reading frames (ORFs)6, 9A, 10, 21, 31, 39, 50, 52, 55, 59, 62, and 64. Of these,15 base substitutions, leading to eight amino acid substitutions,were in the gene 62 region alone. Further DNA sequence analysisshowed that these substitutions were specific for V-Oka andwere not present in nine clinical isolates. The immediate-earlygene 62 product (IE62) of P-Oka had stronger transactivationalactivity than the mutant IE62 contained in V-Oka in 293 andCV-1 cells. An infectious center assay of a plaque-purifiedclone (S7-01) from the V-Oka with 8 amino acid substitutionsin ORF 62 showed smaller plaque formation and less-efficientvirus-spreading activity than did P-Oka in human embryonic lungcells. Another clone (S-13) with only five substitutions inORF 62 spread slightly faster than S7-01 but not as effectivelyas P-Oka. Moreover, transient luciferase assay in 293 cellsshowed that transactivational activities of IE62s of S7-01 andS7-13 were lower than that of P-Oka. Based on these results,it appears that amino acid substitutions in ORF 62 are responsiblefor virus growth and spreading from infected to uninfected cells. Furthermore, the Oka vaccine virus was completely distinguishable from P-Oka and 54 clinical isolates by seven restriction-enzyme fragment length polymorphisms that detected differences in theDNA sequence.

* Corresponding author. Mailing address: Department of Microbiology, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. Phone: 81-6-6879-3321. Fax: 81-6-6879-3329. E-mail: yamanisi@micro.med.osaka-u.ac.jp.

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