The objective of this proposal is to study the relationship between the structural and functional domains of the proteins of a DNA tumor virus, Simian virus 40, during assembly and morphogenesis. We have evidence which suggests that: (1) initiation of oligomerization of a major structural protein, Vpl, occurs immediately after synthesis in the cytoplasm; (2) interaction of the minor coat proteins Vp2 and Vp3 with Vpl occurs in the cytoplasm; (3) partially assembled viral complexes are transported to the nucleus; (4) cellular proteins may catalyze cytoplasmic viral protein assembly and trafficking; and (5) maturation of pre-assembled viral proteins to SV40 minichromosomes occurs in the nucleus. We will test our hypothesis that each viral protein contains several sub-sequences that play specific roles in the molecular interactions enumerated above, that lead to the morphogenesis of virions. We will use various molecular biological, biochemical, and cell biological procedures to define individual domains and relate them to their biological activities. Understanding how these assembly, trafficking, and cellular localization processes are controlled is central to the understanding of the cell biology of gene expression. Aberrations in these biological processes lead to alterations in the normal cell proliferation that controls differentiation and development, and eventually lead to cell death or cancer. Additionally, understanding the fundamental aspects of the structure-function relationships of viral proteins in virion assembly should contribute, in general, to the methods used for the prevention of infectious diseases.
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