Mapping the genetic region coding for herpes simplex virus resistance to mouse interferon alpha/beta.
Mapping the genetic region coding for herpes simplex virus resistance to mouse interferon alpha/beta.
复制标题
绘制单纯疱疹病毒对小鼠干扰素α/β抗性的遗传区域编码图。
DOI：
10.1099/0022-1317-74-11-2325
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Lausch,RN
中科院分区：
文献类型：
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作者：
Su,YH;Oakes,JE;Lausch,RN
单纯疱疹病毒眼部毒力与小鼠干扰素-α/β的菌株敏感性有关。为了鉴定病毒基因组中与对这种细胞因子的高抵抗力相关的区域，用无毒、干扰素敏感的1型单纯疱疹病毒(35株)的完整基因组和强毒、耐干扰素的2型单纯疱疹病毒(186株)的XbaI酶切DNA构建了异型重组体。在小鼠眼组织中分离到一种异型重组病毒，命名为HSV-R4，其滴度可达HSV-1(35)的10~100倍，并可引起间质角膜炎。重组病毒对小鼠干扰素-α/β的抵抗力比单纯疱疹病毒1型(35)高几个数量级，除单纯疱疹病毒2型(186)的12kb片段(0.15~0.23map单位)外，其余均由单纯疱疹病毒1型(35)DNA组成。为了进一步确定干扰素抗性位点，从HSV-2(186)基因组中构建了该12kb片段的3个重叠亚克隆，并进行了标记抢救实验。克隆的BamHI D片段是体内唯一促进HSV-1(35)眼部生长的亚克隆。从35×186BamHI D转基因后代库中分离到一种跨型重组病毒，命名为HSV-R(BD)。与单纯疱疹病毒1型(35)相比，该重组病毒在体外对小鼠干扰素-α/β抑制的抵抗力提高了几个数量级，在小鼠眼组织中的生长速度提高了10-100倍，并在BALB/c小鼠中引起了严重的坏死性基质角膜炎。对重组基因组的分析表明，导致HSV-R(BD)对干扰素抗性的HSV-2基因信息位于BamHI D片段中，很可能定位于含有三个部分开放阅读框的区域，分别为UL14、UL15和UL16。该区域编码的产物仍有待鉴定。
Herpes simplex virus (HSV) ocular virulence has been associated with strain sensitivity to mouse interferon (IFN)-α/β. To identifiy the region of the virus genome associated with heightened resistance to this cytokine, intertypic recombinants were constructed using the intact genome of avirulent, IFN-sensitive HSV type 1 (strain 35) andXbaI-digested DNA from virulent, IFN-resistant HSV type 2 (strain 186). An intertypic recombinant, designated HSV-R4, was isolated which grew to titres 10- to 100-fold higher than HSV-1(35) in mouse ocular tissuein vivo, and induced stromal keratitis. The recombinant which was several orders of magnitude more resistant to mouse IFN-α/βthan HSV-1(35) had a genome composed of HSV-1(35) DNA except for a 12 kb fragment (0.15 to 0.23 map units) derived from HSV-2(186). To define the IFN resistance locus further, three overlapping subclones of this 12 kb fragment were constructed from the HSV-2(186) genome and subjected to marker rescue experiments. The clonedBamHI D fragment was the only subclone that promoted HSV-1(35) ocular growthin vivo. An intertypic recombinant, designated HSV-R(BD), was isolated from the 35 × 186BamHI D transfection progeny pool. This recombinant, in contrast to HSV-1(35), was several orders of magnitude more resistant to mouse IFN-α/βinhibitionin vitro, grew 10- to 100-fold better in mouse ocular tissuein vivo, and caused severe necrotizing stromal keratitis in BALB/c mice. Analysis of the recombinant genome indicated that the HSV-2 genetic information responsible for IFN resistance of HSV-R(BD) was located within theBamHI D fragment, most likely mapping to that region containing three partial open reading frames designated UL14, UL15 and UL16. The products encoded by this region remain to be identified.