Shikova E, Lin Y C, Saha K, Brooks B R, Wong P K
University of Texas M. D. Anderson Cancer Center, Smithville 78957.
J Virol. 1993 Mar;67(3):1137-47. doi: 10.1128/JVI.67.3.1137-1147.1993.
ts1 is a highly neuropathogenic and lymphocytopathic mutant of Moloney murine leukemia virus TB (MoMuLV-TB). We previously reported that the primary neuropathogenic determinant of ts1 maps to a single amino acid substitution, Val-25-->Ile, in precursor envelope protein gPr80env. This Val-25-->Ile substitution apparently renders gPr80env inefficient for transport from the endoplasmic reticulum to the Golgi apparatus. These findings suggest that the cytopathic effect of ts1 in neural cells might be due to the accumulation of gPr80env in the endoplasmic reticulum. Since endothelial and glial cells are targets of ts1 infection in the central nervous system, we established primary endothelial and astrocyte cultures to investigate the mechanism of cell killing caused by ts1. A continuous cell line, TB, was used as a control. Our results showed that both ts1 and MoMuLV-TB replicated and induced a cytopathic effect in astrocyte cultures, albeit to different degrees; ts1 appeared to be more lethal than MoMuLV-TB. On the other hand, ts1 and MoMuLV-TB infections of endothelial or TB cells were not cytopathic. The cytopathic effect in infected astrocytes correlated with the inefficiency of gPr80env transport and the intracellular accumulation of gPr80env as well as aberrant virus particles.
ts1是莫洛尼鼠白血病病毒TB（MoMuLV-TB）的一种高度神经致病和淋巴细胞致病的突变体。我们之前报道过，ts1的主要神经致病决定因素定位在前体包膜蛋白gPr80env中的一个单氨基酸取代，即Val-25→Ile。这种Val-25→Ile取代显然使gPr80env从内质网运输到高尔基体的效率低下。这些发现表明，ts1在神经细胞中的细胞病变效应可能是由于gPr80env在内质网中的积累。由于内皮细胞和神经胶质细胞是ts1在中枢神经系统中的感染靶点，我们建立了原代内皮细胞和星形胶质细胞培养物来研究ts1引起细胞杀伤的机制。使用连续细胞系TB作为对照。我们的结果表明，ts1和MoMuLV-TB在星形胶质细胞培养物中均能复制并诱导细胞病变效应，尽管程度不同；ts1似乎比MoMuLV-TB更具致死性。另一方面，ts1和MoMuLV-TB感染内皮细胞或TB细胞不会产生细胞病变效应。感染星形胶质细胞中的细胞病变效应与gPr80env运输效率低下、gPr80env的细胞内积累以及异常病毒颗粒相关。
