title: Capsid-binding retrovirus restriction factors: discovery, restriction specificity and implications for the development of novel therapeutics.
abstract: The development of drugs against human immunodeficiency virus type 1 infection has been highly successful, and numerous combinational treatments are currently available. However, the risk of the emergence of resistance and the toxic effects associated with prolonged use of antiretroviral therapies have emphasized the need to consider alternative approaches. One possible area of investigation is provided by the properties of restriction factors, cellular proteins that protect organisms against retroviral infection. Many show potent viral inhibition. Here, we describe the discovery, properties and possible therapeutic uses of the group of restriction factors known to interact with the capsid core of incoming retroviruses. This group comprises Fv1, TRIM5α and TRIMCypA: proteins that all act shortly after virus entry into the target cell and block virus replication at different stages prior to integration of viral DNA into the host chromosome. They have different origins and specificities, but share general structural features required for restriction, with an N-terminal multimerization domain and a C-terminal capsid-binding domain. Their overall efficacy makes it reasonable to ask whether they might provide a framework for developing novel antiretroviral strategies.
authors.affiliation: Division of Virology, MRC National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Sanz-Ramos
authors.affiliation: Department of Medicine, Imperial College London, London W2 1PG, UK.|Division of Virology, MRC National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Stoye
mesh_terms: D000818:Animals; D000090103:Antiviral Restriction Factors; D002213:Capsid / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism / Q000627:therapeutic use*; D002460:Cell Line; D006801:Humans; D051379:Mice; D011506:Proteins / Q000378:metabolism / Q000627:therapeutic use*; D012190:Retroviridae / Q000187:drug effects* / Q000378:metabolism; D012192:Retroviridae Infections / Q000188:drug therapy*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; C103189:Fv1 protein, mouse; D011506:Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases