Carmo C R, Esteves P J, Ferrand N, van der Loo W
Departamento de Zoologia e Antropologia-, Faculdade de Ciências da Universidade do Porto, Porto, Portugal.
Immunogenetics. 2006 Jun;58(5-6):494-501. doi: 10.1007/s00251-006-0095-4. Epub 2006 Apr 5.
Whereas in its natural host (Sylvilagus sps.) the effects of myxoma virus infections are benign, in European rabbit (Oryctolagus cuniculus), it causes a highly infectious disease with very high mortality rate, known as myxomatosis. There is evidence that, as with HIV-1 virus in human, myxoma virus may use chemokine receptors such as CCR5 of the host target cell for entry and activation of pathways of immune avoidance. We have characterized and compared CCR5 genes of leporid species with different susceptibility levels to myxomatosis. The CCR5 protein of O. cuniculus differs markedly from all those known from other species. The most striking was the replacement of a specific peptide motif of the second extracellular loop (ECL2) by a motif, which in other species characterizes the CCR2 molecules. While absent in Sylvilagus and Lepus species, this CCR2 imposed CCR5-ECL2 alteration was observed in all genomes of 25 European rabbits, representing the subspecies O. cuniculus algirus and O. cuniculus cuniculus. Allelic variation at the rabbit CCR5 locus confirmed that the gene conversion predates the subspecies split (1-2 Ma).
虽然黏液瘤病毒感染在其天然宿主（棉尾兔属物种）中产生的影响是良性的，但在欧洲兔（穴兔）中，它会引发一种传染性很强、死亡率极高的疾病，即黏液瘤病。有证据表明，与人类的HIV-1病毒一样，黏液瘤病毒可能利用宿主靶细胞的趋化因子受体（如CCR5）进入细胞并激活免疫逃避途径。我们已经对不同黏液瘤病易感性水平的兔科物种的CCR5基因进行了表征和比较。穴兔的CCR5蛋白与其他所有已知物种的CCR5蛋白明显不同。最显著的是，第二个细胞外环（ECL2）的一个特定肽基序被另一个基序取代，而在其他物种中，这个基序是CCR2分子的特征。虽然在棉尾兔属和兔属物种中不存在，但在代表穴兔亚种阿尔及利亚穴兔和穴兔指名亚种的25只欧洲兔的所有基因组中都观察到了这种CCR2导致的CCR5-ECL2改变。兔CCR5基因座的等位基因变异证实，基因转换发生在亚种分化（100-200万年前）之前。
