Upton C, Macen J L, Maranchuk R A, DeLange A M, McFadden G
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Virology. 1988 Sep;166(1):229-39. doi: 10.1016/0042-6822(88)90164-x.
Malignant rabbit fibroma virus (MRV) has been shown to be a lethal tumorigenic poxvirus of rabbits derived from a recombination event between Shope fibroma virus (SFV), which induces benign fibromas in rabbits, and myxoma virus, the agent of myxomatosis. We have cloned and sequenced all of the MRV recombination junctions, which are located near the left and right terminal inverted repeat (TIR) regions, and present a composite map of the MRV genome with respect to the relevant gene products. The two junctions closet to the MRV termini, at identical positions at the left and right ends, are at nucleotide 5272 and result in an in-frame fusion protein (ORF T-5) in which the N-terminal 232 aa are derived from an SFV sequence linked to a C-terminus derived from myxoma. At the left MRV TIR the recombination junction distal from the terminus maps to nucleotide 9946 but leaves the adjacent gene virtually unchanged from its SFV homolog. At the right terminus, the relevant junction sequences from MRV and myxoma could not be cloned in wild-type Escherichia coli but were maintained stably in a recA recBC sbcB host. The SFV/myxoma junction at this location maps 5' to a growth factor gene (SFGF) which is related to those encoding epidermal growth factor and transforming growth factor-alpha. As a result, the myxoma growth factor gene has been deleted in MRV and replaced in toto by the SFV gene. The recombination junction upstream from the SFGF gene creates an in-frame fusion in ORF T11-R in which the N-terminal amino acids are derived from myxoma and the remainder from SFV. In summary, MRV has received the following ORFs from SFV: at the left terminus T5 (fusion), T6, T7, and T8; at the right terminus, T5 (fusion), T6, T7, T8, T9-R, SFGF, and T11-R (fusion).
恶性兔纤维瘤病毒（MRV）已被证明是一种致死性致瘤痘病毒，源自兔纤维瘤病毒（SFV，可在兔体内诱发良性纤维瘤）与黏液瘤病毒（黏液瘤病病原体）之间的重组事件。我们已克隆并测序了所有MRV重组连接点，这些连接点位于左右末端反向重复（TIR）区域附近，并给出了MRV基因组相对于相关基因产物的复合图谱。最靠近MRV末端的两个连接点，在左右两端的相同位置，位于核苷酸5272处，产生一个读码框内融合蛋白（ORF T-5），其中N端的232个氨基酸源自SFV序列，与源自黏液瘤的C端相连。在MRV左TIR处，远离末端的重组连接点定位于核苷酸9946，但相邻基因与其SFV同源物几乎没有变化。在右端，来自MRV和黏液瘤的相关连接点序列无法在野生型大肠杆菌中克隆，但在recA recBC sbcB宿主中稳定维持。该位置的SFV/黏液瘤连接点位于一个生长因子基因（SFGF）的5'端，该基因与编码表皮生长因子和转化生长因子-α的基因相关。结果，黏液瘤生长因子基因在MRV中被删除，并被SFV基因完全取代。SFGF基因上游的重组连接点在ORF T11-R中产生一个读码框内融合，其中N端氨基酸源自黏液瘤，其余部分源自SFV。总之，MRV从SFV获得了以下ORF：在左端为T5（融合）、T6、T7和T8；在右端为T5（融合）、T6、T7、T8、T9-R、SFGF和T11-R（融合）。
