Immunogenicity of herpes simplex virus glycoproteins gC and gB and their role in protective immunity.
Immunogenicity of herpes simplex virus glycoproteins gC and gB and their role in protective immunity.
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单纯疱疹病毒糖蛋白 gC 和 gB 的免疫原性及其在保护性免疫中的作用。
DOI：
10.1128/jvi.50.3.805-812.1984
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发表时间：
1984
影响因子：
5.4
通讯作者：
Levine,M
中科院分区：
文献类型：
--
作者：
Glorioso,J;Schroder,CH;Kumel,G;Szczesiul,M;Levine,M
在BALB/c小鼠中，通过使用科斯突变体在感染过程中在细胞表面膜上呈递这些抗原的能力改变，分析了单个单纯疱疹病毒1型（科斯）糖蛋白gC和gB的相对抗原性。所用的突变体如下：syn LD 70，一种在细胞表面膜gC合成中有缺陷的非温度敏感性突变体; tsF 13，一种在39 ℃下gB前体形式加工成成熟细胞表面形式中有缺陷的温度敏感性突变体;和TS 606，一种在包括糖蛋白在内的所有早期和晚期蛋白质的产生中有缺陷的立即早期温度敏感突变体。通过比较在39 ℃下用野生型病毒感染的小鼠3 T3细胞对免疫溶解的相对易感性，所述野生型病毒呈递糖蛋白抗原gC、gB和gD的完整补体，而用仅呈递这些抗原的子集的突变体感染的靶细胞，我们确定了超免疫抗单纯疱疹病毒1型（科斯）中所含的溶细胞抗体的主要部分，小鼠抗血清针对糖蛋白gC和gB。在BALB/c小鼠中比较了野生型和突变型病毒感染细胞的相对免疫原性。缺乏成熟形式的gB的免疫原诱导的溶细胞抗体滴度与野生型病毒相当，而缺乏成熟形式的gC显示滴度降低70%。免疫原制剂中缺乏成熟细胞表面形式的gB和gC导致病毒中和滴度降低4- 15倍。用ts 606感染的细胞（39 ℃）免疫的动物诱导相对较少的病毒特异性细胞溶解和中和抗体。通过放射免疫沉淀分析这些抗血清的糖蛋白特异性表明，免疫沉淀的抗原反映了免疫原的病毒质膜糖蛋白谱。免疫制剂中缺乏成熟形式的gC或gB不会明显影响对其他抗原的免疫沉淀抗体应答。用野生型和突变病毒感染的细胞免疫小鼠，测试其对1型单纯疱疹病毒的高毒力WAL株的颅内和腹腔内攻击的抗性。尽管观察到单个免疫原诱导的血清病毒特异性抗体发生变化，但所有动物均在10 - 50%致死剂量的腹腔内攻击中存活。然而，颅内激发后动物的存活率存在差异。（400字处截断摘要）
The relative antigenicity of the individual herpes simplex virus type 1 (KOS) glycoproteins gC and gB was analyzed in BALB/c mice by using KOS mutants altered in their ability to present these antigens on cell surface membranes during infection. The mutants employed were as follows: syn LD70 , a non-temperature-sensitive mutant defective in the synthesis of cell surface membrane gC; tsF13 , a temperature-sensitive mutant defective in the processing of the precursor form of gB to the mature cell surface form at 39 degrees C; and ts606 , an immediate early temperature-sensitive mutant defective in the production of all early and late proteins including the glycoproteins. By comparing the relative susceptibility to immunolysis of mouse 3T3 cells infected at 39 degrees C with wild-type virus, presenting the full complement of the glycoprotein antigens, gC, gB, and gD, with target cells infected with mutants presenting only subsets of these antigens, we determined that a major portion of cytolytic antibody contained in hyperimmune anti-herpes simplex virus type 1 (KOS) mouse antiserum was directed against glycoproteins gC and gB. The relative immunogenicity of wild-type and mutant virus-infected cells also was compared in BALB/c mice. Immunogen lacking the mature form of gB induced a cytolytic antibody titer comparable to that of the wild-type virus, whereas that lacking the mature form of gC showed a 70% reduction in titer. The absence of the mature cell surface forms of gB and gC in immunogen preparations resulted in a 4- to 15-fold reduction in in virus neutralizing titer. Animals immunized with ts606 -infected cells (39 degrees C) induced relatively little virus-specific cytolytic and neutralizing antibody. Analysis of the glycoprotein specificities of these antisera by radioimmunoprecipitation showed that the antigens immunoprecipitated reflected the viral plasma membrane glycoprotein profiles of the immunogens. The absence of the mature forms of gC or gB in the immunizing preparation did not appreciably affect the immunoprecipitating antibody response to other antigens. Mice immunized with wild-type and mutant virus-infected cells were tested for their resistance to intracranial and intraperitoneal challenge with the highly virulent WAL strain of herpes simplex virus type 1. Despite the observed alterations in serum virus-specific antibody induced with the individual immunogens, all animals survived an intraperitoneal challenge of 10 50% lethal doses. However, differences in the survival of animals were obtained upon intracranial challenge.(ABSTRACT TRUNCATED AT 400 WORDS)