A virus initiates infection by binding to its specific receptor on the surface of a susceptible cell. Many viruses then enter the cell by receptor-mediated endocytosis, in which the virus-receptor complexes concentrate in clathrin-coated pits which constitutively invaginate to form intracellular vesicles.
Our research showed that entry of the tumor virus simian virus 40 (SV40) differs in important ways from the usual coated pit-mediated process. First, SV40 enters cells through non-coated plasma membrane invaginations called caveolae. Second, SV40 entry is induced by a signal that the virus transmits from the cell surface. Unlike coated pits, the functions of caveolae are not yet clear, although they have been implicated in both endocytosis and transmembrane signaling.
Leonard C. Norkin
Virus Entry through Cavaelae; Transmembrane
Signaling
A major goal of our research is to determine how the SV40-induced transmembrane signal actually promotes SV40 entry through caveolae. Our current work suggests that the signal enables SV40 to enter preformed empty caveolae. However, we need to identify the mediators and membrane targets of the signal. Also, we need to determine whether the signal also promotes downstream events in the entry pathway, such as budding of the caveolae and docking with intracellular targets.
This work is important because it is characterizing a previously unknown virus entry pathway and because it focuses on the not well-understood cellular mechanism of endocytosis through non-coated vesicles.
Methods used in our work include northern and western blotting, in vitro kinase reactions, immunocytochemistry, electron microscopy, and PCR in situ.
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