HIV Interactions with Host Cell Proteins
The authors seek to understand the assembly process of human immunodeficiency virus (HIV) and to develop a vaccine that can effectively neutralize HIV. HIV assembly is a process directed by the viral Gag polyprotein. Gag is a myristoylated precursor protein that is translated in the cytoplasm and then traffics to the plasma membrane or to endosomal vesicles for assembly. The authors have recently described an interaction between Gag and the delta subunit of the AP-3 adaptor protein complex (1). The mechanism and structural basis for this interaction is now under intense study. Our hypothesis is that the AP-3 interaction is responsible for the trafficking of Gag to the multivesicular body (MVB) and that this event is part of a normal productive particle assembly pathway. The Vpu protein of HIV assists the virus assembly process through a poorly-defined mechanism. The authors have presented evidence that Vpu overcomes a host cell restriction to assembly (2). Vpu appears to act through interactions with the recycling pathways in the cell, rather than directly interacting with Gag (3). The nature of the host restriction to assembly that Vpu overcomes is a focus of our ongoing work.