Interactions between SIVNef, SIVGagPol and Alix correlate with viral replication and progression to AIDS in rhesus macaques.
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.
Jesus da Costa
Luciana
L
Departamento de Virologia, IMPPG, Universidade Federal do Rio de Janeiro, Brazil. ljcosta@micro.ufrj.br
Lopes Dos Santos
Adriana
A
Mandic
Robert
R
Shaw
Karen
K
Santana de Aguiar
Renato
R
Tanuri
Amilcar
A
Luciw
Paul A
PA
Peterlin
B Matija
BM
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
D002135:Calcium-Binding Proteins; D015685:Fusion Proteins, gag-pol; D015693:Gene Products, nef; D050505:Mutant Proteins