title: Structural and Functional Properties of the Hepatitis C Virus p7 Viroporin.
abstract: The high prevalence of hepatitis C virus (HCV) infection in the human population has triggered intensive research efforts that have led to the development of curative antiviral therapy. Moreover, HCV has become a role model to study fundamental principles that govern the replication cycle of a positive strand RNA virus. In fact, for most HCV proteins high-resolution X-ray and NMR (Nuclear Magnetic Resonance)-based structures have been established and profound insights into their biochemical and biological properties have been gained. One example is p7, a small hydrophobic protein that is dispensable for RNA replication, but crucial for the production and release of infectious HCV particles from infected cells. Owing to its ability to insert into membranes and assemble into homo-oligomeric complexes that function as minimalistic ion channels, HCV p7 is a member of the viroporin family. This review compiles the most recent findings related to the structure and dual pore/ion channel activity of p7 of different HCV genotypes. The alternative conformations and topologies proposed for HCV p7 in its monomeric and oligomeric state are described and discussed in detail. We also summarize the different roles p7 might play in the HCV replication cycle and highlight both the ion channel/pore-like function and the additional roles of p7 unrelated to its channel activity. Finally, we discuss possibilities to utilize viroporin inhibitors for antagonizing p7 ion channel/pore-like activity.
authors.affiliation: Department of Infectious Diseases, Molecular Virology, University of Heidelberg, 69120 Heidelberg, Germany. vanesa.madan@med.uni-heidelberg.de.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Madan
authors.affiliation: Department of Infectious Diseases, Molecular Virology, University of Heidelberg, 69120 Heidelberg, Germany. ralf_bartenschlager@med.uni-heidelberg.de.|Division of Virus-Associated Carcinogenesis, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. ralf_bartenschlager@med.uni-heidelberg.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Bartenschlager
mesh_terms: D016174:Hepacivirus / Q000201:enzymology* / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism*; D019065:Virus Assembly; D057074:Virus Release; D000086082:Viroporin Proteins
chemical_list: D014764:Viral Proteins; C088369:p7 protein, Hepatitis C virus; D000086082:Viroporin Proteins
keywords: antiviral target; hepatitis C virus; ion channel activity; oligomeric structure; p7 protein; pore-like function; small membrane protein; viroporins; virus assembly and release