title: Interactions between SIVNef, SIVGagPol and Alix correlate with viral replication and progression to AIDS in rhesus macaques.
abstract: Infection with Simian Immunodeficiency Virus (SIV) leads to high viral loads and progression to Simian AIDS (SAIDS) in rhesus macaques. The viral accessory protein Nef is required for this phenotype in monkeys as well as in HIV-infected humans. Previously, we determined that HIVNef binds HIVGagPol and Alix for optimal viral replication in cells. In this study, we demonstrated that these interactions could correlate with high viral loads leading to SAIDS in the infected host. By infecting rhesus macaques with a mutant SIV(mac239), where sequences in the nef gene that are required for these interactions were mutated, we observed robust viral replication and disease in two out of four monkeys, where they reverted to the wild type genotype and phenotype. These two rhesus macaques also died of SAIDS. Two other monkeys did not progress to disease and continued to harbor mutant nef sequences. We conclude that interactions between Nef, GagPol and Alix contribute to optimal viral replication and progression to disease in the infected host.
authors.affiliation: Departamento de Virologia, IMPPG, Universidade Federal do Rio de Janeiro, Brazil. ljcosta@micro.ufrj.br
authors.forename: Luciana
authors.initials: L
authors.lastname: Jesus da Costa
authors.forename: Adriana
authors.initials: A
authors.lastname: Lopes Dos Santos
authors.forename: Robert
authors.initials: R
authors.lastname: Mandic
authors.forename: Karen
authors.initials: K
authors.lastname: Shaw
authors.forename: Renato
authors.initials: R
authors.lastname: Santana de Aguiar
authors.forename: Amilcar
authors.initials: A
authors.lastname: Tanuri
authors.forename: Paul A
authors.initials: PA
authors.lastname: Luciw
authors.forename: B Matija
authors.initials: BM
authors.lastname: Peterlin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D015685:Fusion Proteins, gag-pol / Q000378:metabolism*; D015693:Gene Products, nef / Q000235:genetics / Q000378:metabolism*; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity*; D019562:Viral Load; D014779:Virus Replication
chemical_list: D002135:Calcium-Binding Proteins; D015685:Fusion Proteins, gag-pol; D015693:Gene Products, nef; D050505:Mutant Proteins