Distal Leucines Are Key Functional Determinants of Alix-Binding Simian Immunodeficiency Virus SIVsmE543 and SIVmac239 Type 3 L Domains

In addition to PTAP L domains, primate lentiviruses carry Alix-binding motifs that include the recently described type 3 SREKPYKEVTEDLLHLNSLF sequence. We examined the requirements for the type 3 sequence motif in simian immunodeficiency virus SIVsmE543 and identified the 499LNSLF503 sequence as a key functional determinant. Mutation of distal leucines 499L and 502L (LL mutant) caused an inhibitory effect on Alix-dependent SIVsmE543 release that was quantitatively similar to that observed following disruption of the type 3 L domain or RNA interference (RNAi) depletion of Alix. Similar results were obtained with the SIVmac239 LL mutant. Thus, distal leucines are key determinants of SIVsmE543 and SIVmac239 type 3 L domains.