Yamada Shinya, Matsumoto Yasunobu, Takashima Yasuhiro, Otsuka Haruki
Department of Global Agricultural Science, University of Tokyo, Yayoi 1-1-1, 113-8657, Tokyo, Bunkyo-ku, Japan.
Virus Genes. 2005 Aug;31(1):107-11. doi: 10.1007/s11262-005-2206-y.
The guanine and cytosine content (GC-content) of alpha-herpesvirus genes are highly variable despite similar genome structures. It is known that drug resistant HSV, which has the genome with a high GC-content (approximately 70%), commonly includes frameshift mutations in homopolymer stretches of guanine (G) and cytosine (C) within the thymidine kinase (TK) gene. However, whether such mutation hotspots exist in the TK gene of canine herpesvirus (CHV) which has a low GC-content was unknown. In this study, we investigated mutations in the TK gene of CHV. CHV was passaged in the presence of iodo-deoxyuridine (IDU), and IDU-resistant clones were isolated. In all IDU-resistant virus clones, mutations in the TK gene were observed. The majority of these mutations were frameshift mutations of an adenine (A) insertion or deletion within either of 2 stretches of eight A's in the TK gene. It was demonstrated that CHV TK mutations frequently occur at a limited number of hot spots within long homopolymer nucleotide stretches.
尽管α-疱疹病毒基因的基因组结构相似，但其鸟嘌呤和胞嘧啶含量（GC含量）却高度可变。已知具有高GC含量（约70%）基因组的耐药单纯疱疹病毒（HSV）通常在胸苷激酶（TK）基因内鸟嘌呤（G）和胞嘧啶（C）的同聚物延伸中包含移码突变。然而，GC含量低的犬疱疹病毒（CHV）的TK基因中是否存在此类突变热点尚不清楚。在本研究中，我们调查了CHV的TK基因中的突变。CHV在碘脱氧尿苷（IDU）存在的情况下传代，并分离出对IDU耐药的克隆。在所有对IDU耐药的病毒克隆中，均观察到TK基因中的突变。这些突变大多数是在TK基因中两个由八个A组成的延伸段之一内发生腺嘌呤（A）插入或缺失的移码突变。结果表明，CHV TK突变经常发生在长同聚物核苷酸延伸段内有限数量的热点处。
