Molecular Characterization of SV40 infection

病毒性疾病是现代世界的主要健康危害。SV 40是一种相对简单的病毒，必须进入哺乳动物细胞才能复制。当它这样做时，它会导致受感染的细胞分裂，从而引发宿主体内的肿瘤形成。该提案旨在了解SV 40如何进入细胞，然后传递到细胞核并在那里复制。大多数病毒已经劫持了现有的途径进入细胞。例如，一些病毒利用细胞从外部培养基中吸收营养的途径。然而，我们已经表明，SV 40使用一个全新的途径，涉及表面坑称为小窝。该途径的后续步骤是未知的，难以研究。我们已经发现了许多抑制SV 40感染的药物。在这个提议中，我们将通过研究这些试剂在细胞中的确切位置来研究感染性进入途径。然后，我们将从细胞内分离病毒，并尝试在体外重建病毒进入途径的一部分。这些研究将提供对病毒进入途径的深入了解，这可能导致对抗病毒性疾病的新治疗策略。此外，对这种从细胞表面到细胞核的通路的研究可能为药物递送和/或基因靶向提供新的途径。

Viral disease is a major health hazard in the modern world. SV40 is a relatively simple virus which must enter mammalian cells in order to replicate. As it does so, it causes the infected cell to divide and hence triggers tumour formation in the host. This proposal is aimed at understanding how SV40 enters cells, and then passes to the nucleus where it replicates. Most viruses have hijacked existing pathways into cells. For example, some viruses have used the pathway by which cells take up nutrients from the external medium. However, we have shown that SV40 uses a completely novel pathway involving surface pits called caveolae. The subsequent steps in the pathway are unknown and have been difficult to study. We have discovered a number of agents which inhibit infection by SV40. In this proposal we will characterise the infectious entry pathway by investigating exactly where in the cell these agents work. We will then isolate the virus from within the cell and attempt to reconstitute part of the viral entry pathway in vitro. These studies will provide insights into the entry pathway of the virus which may lead to new therapeutic strategies to combat viral disease. In addition, study of this pathway, leading from the cell surface to the nucleus, may provide new avenues for drug delivery and-or gene targetting.