Centro de Investigación en Sanidad Animal (CISA-INIA), Madrid, Spain.
INRA, UMR 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France.
mBio. 2021 Mar 16;12(2):e03508-20. doi: 10.1128/mBio.03508-20.
Early studies in transgenic mouse lines have shown that the coexpression of endogenous murine prion protein (PrP) and transgenic PrP from another species either inhibits or allows the propagation of prions, depending on the infecting prion strain and interacting protein species. The way whereby this phenomenon, so-called "interference," is modulated remains to be determined. In this study, different transgenic mouse lines were crossbred to produce mice coexpressing bovine and porcine PrP, bovine and murine PrP, or murine and porcine PrP These animals and their respective hemizygous controls were inoculated with several prion strains from different sources (cattle, mice, and pigs) to examine the effects of the simultaneous presence of PrP from two different species. Our results indicate interference with the infection process, manifested as extended survival times and reduced attack rates. The interference with the infectious process was reduced or absent when the potentiality interfering PrP species was efficiently converted by the inoculated agent. However, the propagation of the endogenous murine PrP was favored, allowing us to speculate that host-specific factors may disturb the interference caused by the coexpression of an exogenous second PrP Prion propagation can be interfered with by the expression of a second prion protein in the host. In the present study, we investigated prion propagation in a host expressing two different prion protein genes. Our findings indicate that the ability of the second prion protein to interfere with prion propagation is related to the transmissibility of the prion in the host expressing only the interfering prion protein. The interference detected occurs in a prion strain-dependent manner. Interestingly, a bias favoring the propagation of the murine PrP allele has been observed. These results open the door to future studies in order to determine the role of host factors other than the PrP amino acid sequence in the interference in prion propagation.
早期的转基因小鼠研究表明，内源性鼠朊蛋白（PrP）与另一种物种的转基因 PrP 的共表达，取决于感染的朊病毒株和相互作用的蛋白种类，要么抑制要么允许朊病毒的传播。这种现象，即所谓的“干扰”，是如何被调节的仍有待确定。在这项研究中，不同的转基因小鼠系被杂交，以产生共表达牛和猪 PrP、牛和鼠 PrP 或鼠和猪 PrP 的小鼠。这些动物及其各自的半合子对照被接种了来自不同来源（牛、鼠和猪）的几种朊病毒株，以检查两种不同物种的 PrP 同时存在对感染过程的影响。我们的结果表明，干扰了感染过程，表现为延长的存活时间和降低的攻击率。当接种剂有效地将潜在干扰的 PrP 物种转化时，这种对感染过程的干扰会减少或消失。然而，内源性鼠 PrP 的增殖得到了促进，这使我们推测宿主特异性因素可能会干扰由外源性第二种 PrP 共表达引起的干扰。朊病毒的增殖可以通过宿主中第二种朊病毒蛋白的表达而受到干扰。在本研究中，我们研究了在表达两种不同朊病毒蛋白基因的宿主中朊病毒的增殖。我们的发现表明，第二种朊病毒蛋白干扰朊病毒增殖的能力与在仅表达干扰性朊病毒蛋白的宿主中朊病毒的传染性有关。检测到的干扰以朊病毒株依赖性的方式发生。有趣的是，观察到有利于鼠 PrP 等位基因增殖的偏向。这些结果为未来的研究打开了大门，以便确定除 PrP 氨基酸序列以外的宿主因素在朊病毒增殖中的干扰作用。
