Analysis of human interferon resistant genes of herpes simplex virus

单纯疱疹病毒人干扰素抗性基因分析

• 批准号: 07807037
• 负责人: ARAO Yujiro
• 金额: $ 1.34万
• 依托单位: National Institute of Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07807037/
• 关键词: Herpes simplex virus type 1; Herpes simplex virus type 2; Human interferon alpha; Human interferon beta; Human interferon gamma; interferon resistance; Intertypic recombinant virus; Marker rescue

To better understand how herpes simplex virus (HSV) counteracts anti-HSV effects of interferons (IFNs), first, the sensitivity of 19 HSV strains to type I and II IFNs was compared in the infection processes of cultured human epithelial cells. There was good correlation between the sensitivities to the IFNs although they have different anti-HSV actions. This correlation was not due to induction of endogenous type I IFN by type II IFN treatment, because a neutralizing antibody to IFN beta did not diminish the anti-HSV effects of type II IFN.A similar correlation also was observed in human embryonic lung fibroblast cells. These results suggest that HSV has an ability to overcome the anti-HSV actions of both types of IFNs independently but with similar sensitivity.Secomd, we examined complementation and recombination between two interferon (IFN) sensitive strains, 17syn of herpes simplex virus type 1 [HSV-1 (17syn)] and UW268 of HSV type 2 [HSV-2 (UW268)]. Double infection with the two str … More ains resists reduction in virus yield by IFN.Intertypic recombinants with restored IFN resistance were obtained from progeny viruses in the doubly-infected cultures. These results indicate that IFN resistance of HSV is controlled by at least two genetic regions.Third, restriction endonuclease analysis of the intertypic recombinants deduced that one of the HSV coding regions for IFN resistance locates in BamHI-A,BglII-N or the neighboring fragments of HSV-2. Four cloned fragments, Bam HI-A and-E and BglII-I and-N,of an IFN resistant HSV-2 strain, G[HSV-2 (G)] were tested for their abilities to rescue IFN resistance of HSV-2 (UW268), resulting in that only BglII-N incresed plating efficiency of progeny viruses in co-transfected cultures. An IFN resistant HSV-2 clone was obtained from the co-transfected culture with BglII-N of HSV-2 (G) and the HSV-2 clone contained a DNA sequence within the fragment. Therefore, it is concluded that one of the HSV coding regions for IFN resistance locates in the BglII-N fragment of HSV-2. Less

为了更好地了解单纯疱疹病毒（HSV）如何抵消干扰素（ifn）的抗HSV作用，首先比较了19株HSV在培养的人上皮细胞感染过程中对I型和II型干扰素的敏感性。尽管干扰素具有不同的抗hsv作用，但它们对干扰素的敏感性之间存在良好的相关性。这种相关性不是由于II型IFN治疗诱导内源性I型IFN，因为IFN β的中和抗体并没有减弱II型IFN的抗hsv作用。在人胚胎肺成纤维细胞中也观察到类似的相关性。这些结果表明，HSV具有独立克服两种类型ifn的抗HSV作用的能力，但具有相似的敏感性。其次，我们检测了两种干扰素（IFN）敏感菌株，单纯疱疹病毒1型的17syn [HSV-1 (17syn)]和HSV 2型的UW268 [HSV-2 (UW268)]之间的互补和重组。两株菌株的双重感染可抵抗干扰素对病毒产量的降低。在双重感染的培养中，从子代病毒中获得了恢复IFN抗性的型间重组体。这些结果表明，HSV的IFN耐药性至少受两个遗传区域的控制。第三，通过型间重组体的限制性内切酶分析，推断HSV对IFN耐药的编码区之一位于HSV-2的BamHI-A、BglII-N或邻近片段。对抗干扰素的HSV-2菌株G[HSV-2 (G)]的4个克隆片段Bam HI-A和e以及BglII-I和n进行了测试，以检测它们挽救抗干扰素的HSV-2 （UW268）的能力，结果表明只有BglII-N在共转染的培养物中提高了子代病毒的接种效率。从HSV-2 (G)的BglII-N共转染培养物中获得了一个耐IFN的HSV-2克隆，该克隆片段中含有一个DNA序列。因此，我们认为HSV-2的BglII-N片段可能是HSV对IFN耐药的编码区之一。少

项目成果

Y.Yamaguchi, Y.Arao, T.Kurata, T.Kurimura, H.Kawana, K.Yamanishi, T.Morishima, M.Honda, M.Niimira, R.Hondo, M.Yoshida: "Typing of herpes simplex virus by polymerase chain reaction." Rinsho to Uirusu. 24. 63-68 (1996)

Y.Yamaguchi、Y.Arao、T.Kurata、T.Kurimura、H.Kawana、K.Yamanishi、T.Morishima、M.Honda、M.Niimira、R.Hondo、M.Yoshida：“单纯疱疹病毒的分型

Y.Arao, S.Nii: "Mechanism of establishment of herpes simplex virus latency." Igaku no ayumi. 177. 857-863

Y.Arao，S.Nii：“单纯疱疹病毒潜伏期的建立机制。”

Y.Arao, Y.Ando, M.Narita and T.Kurata: "A similar sensitivity of herpes simplex virus infection to type I and II interferons." Journal of Interferon Research. (in press).

Y.Arao、Y.Ando、M.Narita 和 T.Kurata：“单纯疱疹病毒感染对 I 型和 II 型干扰素具有相似的敏感性。”

山口優樹、荒尾雄二郎、倉田毅、栗村敬、川名尚、山西弘一、森島恒雄、本田まりこ、新村眞人、本藤良、吉田正己: "DNA診断による単純ヘルペスウイルスの型判定" 臨床とウイルス. 24. 63-68 (1996)

Yuki Yamaguchi、Yujiro Arao、Tsuyoshi Kurata、Takashi Kurimura、Nao Kawana、Koichi Yamanishi、Tsuneo Morishima、Mariko Honda、Masato Niimura、Ryo Motodo、Masami Yoshida：“通过 DNA 诊断确定单纯疱疹病毒的类型”临床和病毒学 24。 63-68 (1996)

荒尾雄二郎: "Molecular Medicine" 単純ヘルペスウイルス潜伏感染化の制御因子, 1444-1445 (1996)

荒尾雄二郎：《分子医学》单纯疱疹病毒潜伏感染的控制因素，1444-1445（1996）