Ott D, Friedrich R, Rein A
Laboratory of Molecular Virology and Carcinogenesis, NCI-Frederick Cancer Research Facility, Maryland 21701.
J Virol. 1990 Feb;64(2):757-66. doi: 10.1128/JVI.64.2.757-766.1990.
Viral interference studies have demonstrated the existence of four distinct murine leukemia virus (MuLV) receptors on NIH 3T3 mouse cells. The four viral interference groups are ecotropic MuLV; mink cell focus inducing virus (MCF); amphotropic MuLV; and 10A1, a recombinant derivative of amphotropic MuLV that uses a unique receptor but also retains affinity for the amphotropic MuLV receptor. We report here that 10A1 infects rat and hamster cells, unlike its amphotropic parent. We isolated an infectious molecular clone of 10A1 and present here the sequences of the env genes and enhancer regions of amphotropic MuLV and 10A1. The deduced amino acid sequences of amphotropic MuLV and 10A1 gp70su are remarkably similar to those of MCF and xenotropic MuLV (for which mouse cells lack receptors), with 64% amino acids identical in the four groups. We generated a consensus from these comparisons. Further, the differences are largely localized to a few discrete regions: (i) amphotropic MuLV has two short insertions relative to MCF, at residues 87 to 92 and 163 to 169, and (ii) amphotropic MuLV and MCF are totally different in a hypervariable region, which is greater than 30% proline, at residues approximately 253 to 304. 10A1 closely resembles amphotropic MuLV in its N terminus but contains an MCF-type hypervariable region. These results suggest the possibility that receptor specificity is localized in these short variable regions and further that the unique receptor specificity of 10A1 is due to the novel combination of amphotropic MuLV and MCF sequences rather than to the presence of any novel sequences. The Env proteins of ecotropic MuLV are far more distantly related to those of the other four groups than the latter are to each other. We also found that the enhancer regions of amphotropic MuLV and 10A1 are nearly identical, although 10A1 is far more leukemogenic than amphotropic MuLV.
病毒干扰研究已证明，NIH 3T3小鼠细胞上存在四种不同的鼠白血病病毒（MuLV）受体。这四个病毒干扰组分别是亲嗜性MuLV；貂细胞集落形成诱导病毒（MCF）；兼嗜性MuLV；以及10A1，它是兼嗜性MuLV的重组衍生物，使用独特的受体，但也保留了对兼嗜性MuLV受体的亲和力。我们在此报告，与它的兼嗜性亲本不同，10A1能感染大鼠和仓鼠细胞。我们分离出了10A1的感染性分子克隆，并在此展示了兼嗜性MuLV和10A1的env基因及增强子区域的序列。兼嗜性MuLV和10A1 gp70su的推导氨基酸序列与MCF和异嗜性MuLV（小鼠细胞缺乏其受体）的序列非常相似，这四组中有64%的氨基酸相同。我们从这些比较中得出了一个共识。此外，差异主要集中在几个离散区域：（i）相对于MCF，兼嗜性MuLV在第87至92位残基和第163至169位残基处有两个短插入；（ii）兼嗜性MuLV和MCF在一个高变区完全不同，该高变区脯氨酸含量超过30%，位于大约第253至304位残基处。10A1在其N端与兼嗜性MuLV非常相似，但包含一个MCF型高变区。这些结果表明，受体特异性可能定位于这些短可变区域，进一步表明10A1独特的受体特异性是由于兼嗜性MuLV和MCF序列的新组合，而不是由于任何新序列的存在。亲嗜性MuLV的Env蛋白与其他四组的Env蛋白的亲缘关系远比其他四组之间的亲缘关系远。我们还发现，兼嗜性MuLV和10A1的增强子区域几乎相同，尽管10A1比兼嗜性MuLV更具致白血病性。
