HEPATITIS-B VIRUS PRODUCED BY TRANSFECTED HEP G2 CELLS CAUSES HEPATITIS IN CHIMPANZEES
HEPATITIS-B VIRUS PRODUCED BY TRANSFECTED HEP G2 CELLS CAUSES HEPATITIS IN CHIMPANZEES
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DOI：
10.1073/pnas.84.13.4641
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发表时间：
1987-07-01
影响因子：
11.1
通讯作者：
POPPER, H
中科院分区：
文献类型：
--
作者：
ACS, G;SELLS, MA;POPPER, H
我们已经报道了用含有乙型肝炎病毒（HBV） DNA的质粒转染的Hep G2细胞衍生的克隆细胞在培养基中分泌球形和丝状乙型肝炎表面抗原（HBsAg）、核心颗粒和病毒粒子。在这里，我们描述了典型肝炎的发展，在两只黑猩猩静脉接种的培养基中，转染的细胞已经生长。这些动物的肝脏活组织检查显示薄壁组织和门管区的特征性病变，这些病变在较早的时候在接受了大量病毒粒子的黑猩猩中很明显。一只感染黑猩猩的血清中HBsAg的数量在初次接种后随时间增加，然后随着针对HBsAg和核心抗原的抗体的出现而减少。在整个实验过程中，另一只动物的HBsAg仍可检测到。两种动物的乙型肝炎e型抗原水平在第5周达到峰值，表明感染的急性期。作为坏死性炎症标志物的血清酶活性也有所增加。从患者身上分离出来的病毒粒子的乙肝表面抗原亚型，其DNA被克隆出来，然后用于转染乙肝G2细胞，与在黑猩猩身上发现的病毒粒子相同。此外，从黑猩猩身上分离的病毒DNA的限制性内切酶分析结果与克隆的DNA完全相同。因此，HBV dna转染的hepg2细胞可以支持病毒粒子的复制，从而在黑猩猩中产生肝炎。
We have reported that clonal cells derived from Hep G2 cells transfected with a plasmid containing hepatitis B virus (HBV) DNA secrete spherical and filamentous forms of hepatitis B surface antigen (HBsAg), core particles, and virions into the culture medium. Here we describe the development of typical hepatitis in two chimpanzees following intravenous inoculation with the medium in which the transfected cells had grown. The liver biopsies from these animals showed characteristic lesions in parenchyma and portal tracts, from conspicuous at an earlier time in the chimpanzee that had received a greater number of virions. The amount of HBsAg in the serum of one infected chimpanzee increased with time after the initial inoculation and then decreased concomitantly with the appearance of antibodies against HBsAg and core antigens. HBsAg remained detectable in the other animal throughout the course of the experiment. The levels of hepatitis B "e" antigen in both animals peaked at week 5, signifying the acute phase of the infection. The activities of serum enzymes that are markers for necroinflammation also increased. The hepatitis HBsAg subtype of the virions isolated from the patient whose DNA was cloned and then used for transfection of the Hep G2 cells was the same as that found in the chimpanzees. Furthermore, the restriction enzyme analysis of the viral DNA isolated from the chimpanzees was identical to the cloned DNA. Thus, HBV DNA-transfected Hep G2 cells can support the replication of virions that, in turn, produce hepatitis in chimpanzees.