To infect human cells viruses must overcome the barrier presented by the cell surface. We are studying how viruses overcome this barrier and enter the cell. We have recently shown that SV40 uses a previously undescribed pathway to enter cells. SV40 binds to the cell surface and then appears within caveolae. Our work suggests that the virus has evolved a strategy in which it hijacks the caveolae as a means to gain entry into the cell and ultimately to reach the cell nucleus where it replicates.
Work is in progress to elucidate the steps in the entry pathway which lead to infection.
As well as the medical interest in understanding and blocking this virus transport pathway, these studies are of considerable interest for gene therapy where specific molecules must be delivered from the outside of the cell to the cell nucleus. Muscular dystrophy is characterised by increased membrane fragility and disorganisation of surface domains in muscle cells. We recently identified a major component of the muscle plasma membrane which is associated with caveolae. This protein, caveolin-3, appears to play a key role in the organisation of the sarcolemma and to interact with dystrophin, the protein disrupted in Duchenne Muscular Dystrophy. Moreover, recent work has shown that mutations in caveolin-3 cause some types of muscular dystrophy.