Vaccine potential of a herpes simplex virus type 2 mutant deleted in the PK domain of the large subunit of ribonucleotide reductase (ICP10)
Vaccine potential of a herpes simplex virus type 2 mutant deleted in the PK domain of the large subunit of ribonucleotide reductase (ICP10)
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DOI：
10.1016/s0264-410x(98)00470-8
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发表时间：
1999-04-09
期刊：
影响因子：
5.5
通讯作者：
Smith, CC
中科院分区：
文献类型：
--
作者：
Aurelian, L;Kokuba, H;Smith, CC
单纯疱疹病毒2型(HSV-2)核糖核苷酸还原酶(ICP10)大亚基PK区缺失突变株作为预防HSV-2感染和疾病的疫苗。该病毒命名为ICP10 Delta PK，表达一个95 kDa的ICP10蛋白，缺乏PK活性和转化潜能。ICP10 Delta PK在分裂细胞和未分裂细胞的培养中生长受阻。在分裂细胞中，病毒生长的开始延迟，复制开始于10-15小时P.I.根据感染的多样性，除了生长开始延迟外，病毒复制在非分裂细胞中显著受损(低1000倍)。一株回复病毒(HSV-2(R))表达ICP10，恢复转化活性，具有野生型生长特性。ICP10 Delta PK在感染动物中的生长也受到影响。从感染部位分离于第2天，但不是第7天P.I.病毒滴度(2×10(2)pfu/ml)明显低于单纯疱疹病毒2型(5×10(4)pfu/ml)。注射高滴度ICP10 Delta PK(5×10(7)pfu/FootPad)的小鼠在21天的随访期内仍然没有临床症状并存活下来，并且在30天P.I.潜伏感染的神经节中没有分离到病毒。ICP10 Delta PK免疫的动物产生了HSV特异性体液和T细胞反应，并证明对HSV-2感染和病毒诱导的疾病具有绝对的保护作用。(C)1999爱思唯尔科学有限公司，保留所有权利。
A herpes simplex virus type 2 (HSV-2) mutant deleted in the PK domain of the large subunit of ribonucleotide reductase (ICP10) was evaluated as a potential vaccine for the prevention of HSV-2 infection and disease. This virus, designated ICP10 Delta PK, expressed a 95 kDa ICP10 protein that lacked PK activity and transforming potential. ICP10 Delta PK was growth compromised in dividing and nondividing cells in culture. In dividing cells, onset of virus growth was delayed, with replication initiating at 10-15 h p.i. depending on the multiplicity of infection, In addition to the delayed growth onset, virus replication was significantly impaired (1000-fold lower tilers) in nondividing cells. A revertant virus (HSV-2(R)) expressed ICP10, regained transforming activity and had wild type growth properties. ICP10 Delta PK was growth compromised also in infected animals. It was isolated from the site of infection on day 2, bur not day 7 p.i. and its titers at this time (2 x 10(2) pfu/ml) were significantly lower than those of HSV-2 (5 x 10(4) pfu/ml). Mice given high titers of ICP10 Delta PK (5 x 10(7) pfu/footpad) remained free of clinical symptoms and survived infection during a 21-day follow-up period and virus was not isolated from latently infected ganglia at 30 days p.i. ICP10 Delta PK immunized animals developed HSV-specific humoral and T-cell responses and evidenced absolute protection from HSV-2 infection and virus-induced disease. (C) 1999 Elsevier Science Ltd, All rights reserved.