Parvovirus structure-function relationships (viral cycle and tropism)

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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.