Membrane Traffic Pathways in Viral Replication and Pathogenesis

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Whether direct infections of man or infections that impact on domestic animals, crops or the environment in general, virus infections are a major health and economic burdens for mankind. Viruses require cells for infection and replication. Understanding the various ways in which viruses gain entry to cells, exploit cellular mechanisms for their replication and exert their pathogenic potential is key to intervening in these processes. Our work aims to understand aspects of the cell biology of human immunodeficiency viruses (HIV), the infectious agents associated with AIDS, and the arboviruses Dengue virus and Semliki Forest virus, representatives of two families of viruses transmitted by mosquitoes and currently responsible for wide-spread epidemics in the tropics. We will focus on understanding how a set of cellular proteins can prevent specific events in the entry of these viruses into cells, with a view to exploiting these proteins as natural inhibitors of infection. In parallel, we aim to use knowledge acquired over many years to identify broad-spectrum, small molecule, inhibitors of arbovirus infection that can be used as prophylactics or in epidemic situations. We will continue current work on virus assembly, using new methods to understand the cell biology of virus formation and, for HIV in particular, how modification of key signals in viral proteins, required for correct virus assembly, impact on viral pathogenesis.