Hippenmeyer P J, Rankin A M, Luckow V A, Neises G R
G.D. Searle, St. Louis, Missouri 63198, USA.
J Virol. 1997 Feb;71(2):988-95. doi: 10.1128/JVI.71.2.988-995.1997.
Null mutants and attenuated mutants of herpes simplex virus (HSV) have been shown to induce immunity against challenge from wild-type virus. Null viruses with a defect in late gene products would be expected to express more viral genes than viruses with defects in essential early gene products and thus induce a better immune response. Herpesviruses encode a late gene product (serine protease) that is autocatalytic and cleaves the capsid assembly protein during viral replication. To determine whether a virus with a mutation in this gene could induce immunity, we constructed a recombinant virus containing the gusA reporter gene in the protease domain of the HSV type 1 UL26 open reading frame (ORF). Consistent with previous results (M. Gao, L. Matusick-Kumar, W. Hurlburt, S. F. DiTusa, W. W. Newcomb, J. C. Brown, P. J. McCann, I. Deckman, and R. J. Colonno, J. Virol. 68:3702-3712, 1994), recombinant virus could be isolated only from helper cell lines expressing the product of the UL26 ORF. Mice inoculated with the recombinant virus were unaffected by doses of virus that were lethal to mice infected with wild-type virus. Mice which were previously inoculated with the recombinant virus were also protected by a subsequent challenge with wild-type virus in a dose-dependent manner. These results indicate that recombinant viruses lacking the protease gene are avirulent but render protection from subsequent challenge.
单纯疱疹病毒（HSV）的缺失突变体和减毒突变体已被证明能诱导针对野生型病毒攻击的免疫力。预计晚期基因产物有缺陷的缺失病毒比必需早期基因产物有缺陷的病毒能表达更多病毒基因，从而诱导更好的免疫反应。疱疹病毒编码一种晚期基因产物（丝氨酸蛋白酶），该产物具有自催化作用，并在病毒复制过程中切割衣壳组装蛋白。为了确定该基因发生突变的病毒是否能诱导免疫力，我们构建了一种重组病毒，该病毒在1型单纯疱疹病毒UL26开放阅读框（ORF）的蛋白酶结构域中含有gusA报告基因。与先前的结果一致（M. Gao、L. Matusick-Kumar、W. Hurlburt、S. F. DiTusa、W. W. Newcomb、J. C. Brown、P. J. McCann、I. Deckman和R. J. Colonno，《病毒学杂志》68:3702 - 3712，1994），重组病毒只能从表达UL26 ORF产物的辅助细胞系中分离出来。接种重组病毒的小鼠不受对感染野生型病毒的小鼠致死剂量病毒的影响。先前接种过重组病毒的小鼠也能以剂量依赖的方式受到随后野生型病毒攻击的保护。这些结果表明，缺乏蛋白酶基因的重组病毒无毒，但能提供针对后续攻击的保护。
