Papillomaviruses are a large family of closely related viruses that give rise to warts in their hosts. Infection of the genital tract by the human viruses from this group represents one of the few firmly established links between viral infection and the development of cancer. The bovine papillomavirus, BPV, has served as a prototype for this group especially regarding viral DNA replication, but its relative simplicity serves also to examine mechanistic features of DNA replication in general. This system, whereby a single protein encompasses the key events in replication initiation through its different oligomeric forms, provides a great opportunity to examine these events in detail. Our goals are to build a mechanistic view of the assembly of E1 on the origin of replication and an understanding toward the workings of hexameric helicases in general at an atomic level. In addition, the viral DNA replication machinery itself represents an obvious target for antiviral therapy. Detailed information such as high-resolution structures of viral proteins required for replication will greatly facilitate the development and testing of antiviral agents. Relevance: infection of the genital tract by the human papillomaviruses represents one of the few firmly established links between viral infection and the development of cancer. The bovine papillomavirus, BPV, has served as a prototype for this group especially regarding viral replication. It also enables the understanding of key features in DNA replication in general due to its relative simplicity Our objective is to gain a mechanistic understanding of the events that initiate viral replication. This type of detailed information of viral proteins required for its replication and that can serve as targets for antiviral therapy, will greatly facilitate the development and testing of antiviral agents. Through there have been important recent advances in vaccine development, these may not be effective to a population that has already been infected.
|Enemark, Eric J; Joshua-Tor, Leemor (2008) On helicases and other motor proteins. Curr Opin Struct Biol 18:243-57|
|Sankale, J-L G; Tong, Q; Hadigan, C M et al. (2006) Regulation of adiponectin in adipocytes upon exposure to HIV-1. HIV Med 7:268-74|
|Auster, Anitra S; Joshua-Tor, Leemor (2004) The DNA-binding domain of human papillomavirus type 18 E1. Crystal structure, dimerization, and DNA binding. J Biol Chem 279:3733-42|
|Enemark, Eric J; Stenlund, Arne; Joshua-Tor, Leemor (2002) Crystal structures of two intermediates in the assembly of the papillomavirus replication initiation complex. EMBO J 21:1487-96|