HIV Accessory Proteins: Emerging Therapeutic Targets

Table 1 HIV accessory proteins

	Molecular Weight (kD)	Modifications	Cellular Location	Virus Association	Interacting Cellular Factor(s) (size, kD)	Known/Putative Functions
Nef	27	Myristoylated	Cytoplasm	Yes	lck (56)^a	• Increases virion infectivity
						• Down-regulates surface CD4
Vif	23	?	Cytoplasm	Yes	(?)^b	• Increases virion infectivity
						• Reorganizes cytoskeletal elements
Vpr	14	?	Nucleus	Yes	Rip-1 (41)^c	• Promotes cellular differentiation
					RIP (180)^d	• Arrests cells in G2 phase of cell cycle
						• Interacts with glucocorticoid steroid pathway
						• Prevents cell proliferation during chronic infection
Vpu	16	Phosphorylated	Cytoplasm	?	UBP (69)^e	• Enhances viral export from infected cells via ion channel formation
						• Promotes CD4 degradation in ER

^aNef appears to compete for a CD4 binding site with the p56^lck tyrosine kinase to induce endocytosis of CD4. ^bVif may interact with two uncharacterized cellular factors: (i) a membrane-associated protein which stably anchors Vif on the membrane surface and (ii) a vimentin-associated factor capable of moving a Vif-containing pre-integration complex along intermediate filaments.
^cRip-1 is a cytosolic protein that is translocated to the nucleus by Vpr. Rip-1 coprecipitates with Vpr and the glucocorticoid receptor.
^dRIP is also reported to be involved in Vpr nuclear transport but the exact relationship of Rip-1 and RIP has not yet been established. The fact that both Rip-1 and RIP appear to be involved in Vpr nuclear transport has led to the speculation that the latter represents a multimeric form of Rip-1.
^eUBP shares similarities with the immunophilin family of proteins that includes the cyclophilins and the FK506 binding proteins. It has been speculated that UBP may be involved in the ion channel formation capability of Vpu.

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