Parvovirus structure-function relationships (viral cycle and tropism)

细小病毒感染人类和动物，并以其改变宿主专一性而臭名昭著，导致严重的流行病。一个著名的例子是猫细小病毒，它在20世纪40年代末适应于水貂，在70年代末适应于狗。大多数细小病毒从不同的宿主进入细胞，但在繁殖的后期无法完成病毒周期。猫细小病毒是一个例外，因为它识别特定的细胞(转铁蛋白)受体，只有在突变使它们适应这些宿主特有的受体后才能进入。我们最近观察到，猪细小病毒通过一条新的途径进入不同来源的细胞。这一途径的特征是这项提议的主要主题之一，可能会对许多其他病毒产生影响。另一个被证明对宿主特异性很重要的主题是病毒的形态发生和使有效的病毒组装成为可能的反馈控制机制。我们提出了一种新的途径，通过这种途径，病毒蛋白在合成过程中在均聚物中折叠，从而创建核定位基序，从而避免错误折叠的蛋白质的干扰。这一策略还将对细胞进入和膜破裂产生影响。最后，我们打算阐明一类新的小非结构蛋白的作用，这些蛋白在感染后期起作用。

Parvoviruses infect both humans and animals and are notorious for their ability to change host specificity resulting in serious pandemics. A well-known example is the cat parvovirus that adapted to mink in the late 1940s and to dogs in the late 1970s. Most parvoviruses enter cells from different hosts but fail to complete the viral cycle later in their reproduction. The cat parvovirus is an exception in that it recognizes specific cell (transferrin) receptors and are able to enter only after mutations adapted them to these host-specific receptors. We observed recently that porcine parvoviruses enter cells of different origin by a new pathway. The characterization of this pathway is one of the main topics of this proposal and may have repercussions for many other viruses. Another main topic, shown to be important for host specificity, is viral morphogenesis and the feedback control mechanism that enables an efficient virus assembly. We propose a novel pathway by which viral proteins are folded during synthesis in homopolymers and thus create nuclear localization motifs and thus avoid interference by misfolded proteins. This strategy will also have an impact on cell entry and membrane breaching. Finally, we intend to clarify the role of a new class of small non-structural proteins that have a role late in the infection.