ASSOCIATION OF SIMIAN IMMUNODEFICIENCY VIRUS NEF WITH CELLULAR SERINETHREONINE KINASES IS DISPENSABLE FOR THE DEVELOPMENT OF AIDS IN RHESUS MACAQUES/

The nef gene of simian immunodeficiency virus (SIV) is essential for h igh viral load and induction of AIDS in rhesus monkeys. A mutant form of the SIVmac239 Nef, which contains changes in a putative SH3-binding domain (amino acids 104 and 107 have been changed from PxxP to AxxA), does not associate with cellular serine/threonine kinases, but is ful ly active in CD4 downregulation and associates with the cellular tyros ine kinase Src. Infection of two rhesus macaques with SIVmac239 contai ning the mutant AxxA-Nef caused AIDS and rapid death in both animals. No reversions were observed in the majority of nef sequences analyzed from different time points during infection and from lymphatic tissues at the time of death. Our findings indicate that the putative SH3-lig and domain in SIVmac Nef and the association with cellular serine/thre onine kinases are not important for efficient replication and pathogen icity of SIVmac in rhesus macaques.