Coppola M A, Thomas C Y
Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
J Exp Med. 1990 May 1;171(5):1739-52. doi: 10.1084/jem.171.5.1739.
Heterogeneity in the structure of the envelope proteins has been observed in many human and animal retroviruses and may influence pathogenicity. However, the biological significance of this heterogeneity and the mechanisms by which it is generated are poorly understood. We have studied a mouse model in which the envelope gene structure of lymphoma-associated viruses appears to be controlled by a single host gene. The inoculation of HRS and CWD mice with a leukemogenic murine leukemia virus (MuLV) results in recombination between the injected virus and envelope gene sequences of endogenous retroviruses. The genomes of HRS (class I) env recombinants and CWD (class II) env recombinants differ in the sequences encoding the NH2-terminal portion of the transmembrane envelope protein (TM). We have shown that an HRS gene linked to the MHC on chromosome 17 mediates a dominant selection for recombinant retroviruses with the class I envelope gene structure. CBA mice, which share the H-2k haplotype with HRS, also carry the dominant allele at this locus. This system provides a useful model for studies of host factors involved in the selection of specific variants of pathogenic retroviruses.
在许多人类和动物逆转录病毒中都观察到包膜蛋白结构的异质性，这种异质性可能会影响致病性。然而，这种异质性的生物学意义以及其产生机制却知之甚少。我们研究了一种小鼠模型，其中淋巴瘤相关病毒的包膜基因结构似乎受单个宿主基因控制。用致白血病的鼠白血病病毒（MuLV）接种HRS和CWD小鼠，会导致注入病毒与内源性逆转录病毒的包膜基因序列之间发生重组。HRS（I类）env重组体和CWD（II类）env重组体的基因组在编码跨膜包膜蛋白（TM）氨基末端部分的序列上有所不同。我们已经表明，与17号染色体上的MHC连锁的HRS基因介导了对具有I类包膜基因结构的重组逆转录病毒的显性选择。与HRS共享H-2k单倍型的CBA小鼠在该位点也携带显性等位基因。该系统为研究参与致病性逆转录病毒特定变体选择的宿主因子提供了一个有用的模型。
