Parvovirus structure-function relationships (viral cycle and tropism)

细小病毒感染人类和动物，并因其改变宿主特异性的能力而臭名昭著，导致严重的大流行。一个著名的例子是猫细小病毒，它在20世纪40年代末适应了水貂，在70年代末适应了狗。大多数细小病毒进入来自不同宿主的细胞，但在繁殖后期不能完成病毒周期。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，并且只有在突变使它们适应这些宿主特异性受体后才能进入。我们最近观察到猪细小病毒通过一种新的途径进入不同来源的细胞。该途径的表征是本提案的主要主题之一，并可能对许多其他病毒产生影响。另一个对宿主特异性很重要的主题是病毒形态发生和使病毒有效组装的反馈控制机制。我们提出了一种新的途径，通过该途径，病毒蛋白在均聚物合成过程中折叠，从而产生核定位基序，从而避免被错误折叠的蛋白干扰。这种策略也会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在感染后期的作用。

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.