Rajcáni J, Kúdelová M, Oravcová I, Vojvodová A, Kosovský J, Matis J
Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Folia Microbiol (Praha). 1999;44(6):713-9. doi: 10.1007/BF02825668.
The genetic background of HSZP virus, an HSV1 strain with extensive passage history, was analyzed by parallel comparative sequencing of four relevant genes (UL27/gB, UL41/vhs, UL44/gC and UL53/gK) of HSZP and additional three selected viruses [strains ANGpath, strains KOS(a) and KOS(b) and the prototype strain 17]. Mutation at position 858 (His for Arg) in gB of HSZP was found to be responsible for giant cell formation (syn3gB mutation) similarly as the 855 mutation (Val for Ala) in the gB of ANGpath. No syn1gK mutations were detected in the UL53 gene either of HSZP or of ANGpath viruses. The reduced virulence of HSZP for adult mice after peripheral inoculation, similarly as that of KOS virus, seems to be related (at least in part) to numerous mutations in the gB ectodomain. Of these, two mutations located in the antigenic domain IV were the same in gBHSZP as well as in gBKOS (at amino acids 59 and 79), at least two (amino acids 313 and 553) were specific for gBKOS, while one mutation (Ser for Ala at position 108) was specific for gBHSZP. The abolished shutoff function of the HSZP virus was related to at least four out of six specific mutations seen in the vhs polypeptide (vhsHSZP) encoded by the UL41 gene, of which three (amino acids 374, 386, 392) were clustered in the semiconservative box A of vhsHSZP (the truncation of which abrogates the inhibition provided by this protein) and one mutation (at amino acid 18) was situated in the highly conservative locus I of vhsHSZP. In addition, the two vhsKOS specific mutations (amino acids 19 and 317) not found in vhsHSZP, enhanced the early host shutoff function of the vhsKOS protein. Finally, gCHSZP had two specific mutations (amino acids 137 and 147) located in the antigenic domain II of gC, which is responsible for binding of HSV1 virions to the glycosoaminoglycan (GAG) receptor. When expressed in Sf21 cells using the recombinant baculovirus system (Bac-to-Bac), gCHSZP and gCKOS showed no essential antigenic differences.
通过对HSZP以及另外三种选定病毒（ANGpath株、KOS(a)株和KOS(b)株以及原型株17）的四个相关基因（UL27/gB、UL41/vhs、UL44/gC和UL53/gK）进行平行比较测序，分析了具有广泛传代历史的HSV1毒株HSZP病毒的遗传背景。发现HSZP的gB基因中858位（His突变为Arg）的突变与巨细胞形成（syn3gB突变）有关，这与ANGpath的gB基因中855位（Val突变为Ala）的突变情况类似。在HSZP病毒或ANGpath病毒的UL53基因中均未检测到syn1gK突变。外周接种后HSZP对成年小鼠的毒力降低，与KOS病毒类似，似乎（至少部分）与gB胞外结构域中的大量突变有关。其中，位于抗原结构域IV的两个突变在gBHSZP和gBKOS中相同（第59和79位氨基酸），至少两个（第313和553位氨基酸）是gBKOS特有的，而一个突变（第108位Ser突变为Ala）是gBHSZP特有的。HSZP病毒关闭功能的丧失与UL41基因编码的vhs多肽（vhsHSZP）中六个特定突变中的至少四个有关，其中三个（第374、386、392位氨基酸）聚集在vhsHSZP的半保守框A中（该框的截断消除了该蛋白提供的抑制作用），一个突变（第18位氨基酸）位于vhsHSZP高度保守的位点I。此外，vhsKOS特有的两个突变（第19和317位氨基酸）在vhsHSZP中未发现，增强了vhsKOS蛋白的早期宿主关闭功能。最后，gCHSZP在gC的抗原结构域II中有两个特定突变（第137和147位氨基酸），该结构域负责HSV1病毒粒子与糖胺聚糖（GAG）受体的结合。当使用重组杆状病毒系统（Bac-to-Bac）在Sf21细胞中表达时，gCHSZP和gCKOS没有显示出本质的抗原差异。
