POINT MUTATION IN THE S-GENE OF HEPATITIS-B VIRUS FOR A D/Y OR W/R SUBTYPIC CHANGE IN 2 BLOOD-DONORS CARRYING A SURFACE-ANTIGEN OF COMPOUND SUBTYPE ADYR OR ADWR
POINT MUTATION IN THE S-GENE OF HEPATITIS-B VIRUS FOR A D/Y OR W/R SUBTYPIC CHANGE IN 2 BLOOD-DONORS CARRYING A SURFACE-ANTIGEN OF COMPOUND SUBTYPE ADYR OR ADWR
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DOI：
10.1128/jvi.61.10.3030-3034.1987
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发表时间：
1987-10-01
影响因子：
5.4
通讯作者：
MAYUMI, M
中科院分区：
文献类型：
--
作者：
OKAMOTO, H;IMAI, M;MAYUMI, M
从一名献血者的血浆中克隆出乙型肝炎病毒（HBV）基因组，该献血者携带三种不同亚型的亚病毒颗粒，比例如下：adr， 25%；埃尔,63%;adyr, 12%。HBV DNA克隆根据S基因只有一个核苷酸的差异被分为两组。两个克隆以A为核苷酸365，构成赖氨酸作为氨基酸残基122的部分密码子，并在转染的NIH 3T3细胞中产生adr亚型表面抗原。其余4个克隆有G决定精氨酸的密码子，并在转染细胞中产生ayr亚型的表面抗原。同样，从携带adr（71%）和adwr（29%）亚型亚病毒颗粒的个体血浆中克隆HBV基因组。两个克隆，T和A分别作为核苷酸476和479。其他7个克隆的核苷酸分别为C和G。通过与先前报道的各种亚型HBV基因组的比较，推断出核苷酸479的突变，形成赖氨酸或精氨酸作为氨基酸残基160的部分密码子，分别确定了w或r亚型。将含有adwr亚型表面抗原的血浆衍生的adw或adr亚型基因组分别转染NIH 3T3细胞，然后共培养，产生adw或adr亚型的亚病毒颗粒。然而，当细胞同时转染adw和adr亚型基因组时，在同一颗粒上产生具有w和r决定因子的亚病毒颗粒。这些结果将d/y或w/r亚型变化归因于S基因的点突变，并倾向于肝细胞与HBV基因组及其突变体的共同感染作为复合亚型的机制。
Genomes of hepatitis B virus (HBV) were cloned from the plasma of a blood donor who carried subviral particles of three distinct subtypes in the following proportions: adr, 25%; ayr, 63%; and adyr, 12%. HBV DNA clones were classified into two groups based on a difference at only one nucleotide in the S gene. Two clones had A as nucleotide 365 that formed part of the codon for lysine as amino acid residue 122 and produced a surface antigen of subtype adr in transfected NIH 3T3 cells. The remaining four clones had G determining the codon for arginine and produced a surface antigen of subtype ayr in transfected cells. Similarly, HBV genomes were cloned from the plasma of an individual who carried subviral particles of subtypes adr (71%) and adwr (29%). Two clones and T and A as nucleotides 476 and 479, respectively. The other seven clones had C and G as the respective nucleotides. Based on a comparison with previously reported HBV genomes of various subtypes, the mutation of nucleotide 479, forming part of the codon for lysine or arginine as amino acid residue 160, was deduced to determine the w or r subtype, respectively. When NIH 3T3 cells were transfected separately with the genome of subtypes adw or adr, derived from plasma containing a surface antigen of subtype adwr, and then cocultured, they produced subviral particles of either subtype adw or adr. When cells were transfected with the genomes of subtypes adw and adr simultaneously, however, subviral particles were produced that possessed w and r determinants on the selfsame particles. These results attributed the d/y or w/r subtypic change to a point mutation in the S gene and favored coinfection of hepatocytes with an HBV genome and its mutant as the mechanism of compound subtypes.