The role of Vif during HIV-1 infection: interaction with novel host cellular factors.
BACKGROUND
Current research suggests that human immunodeficiency virus type-1 (HIV-1) virion infectivity factor (Vif) acts during viral assembly in producer cells to ensure infectivity in target cells but the exact mechanism of action has not been defined. Vif interacts with Gag, viral protease and RNA and these interactions are proposed to be important for correct particle assembly and stability of the reverse transcription complex.


OBJECTIVE
The existence of cells that are either permissive or non-permissive for replication of Vif deficient viruses suggests the involvement of host cellular factors in its function. Current research suggests an association of Vif with the intermediate filament protein, vimentin, and the tyrosine kinase, Hck, but the significance of these associations remains to be defined. More recently HP68, a cellular ATP binding protein, has been shown to be important for capsid formation and an interaction between Vif and HP68 has been shown. Our aim was to further identify host cellular factors involved in Vif function.


METHODS
We have employed the yeast 2-hybrid system to identify cellular proteins which interact with HIV-1 Vif. Sixteen clones were isolated from a high stringency yeast-2-hybrid screen of a human leucocyte cDNA library with Vif derived from the T-cell tropic HIV-1 strain NL4.3. Of these, 8 clones were confirmed as specifically binding Vif, fully sequenced and identified via GenBank homology searches.


RESULTS
Thus far 3 of these clones, spermine/spermidine N1-acetyltransferase, Triad 3 and a novel gene which we have termed 'novel Vif binding protein', have been characterised and represent attractive candidates for mediating Vif action during HIV replication.


CONCLUSIONS
Through identification and characterisation of cellular factors interacting with HIV-1 Vif we hope to unravel the mechanism of action of Vif which may ultimately aid therapeutic design.
Lake
Julie-anne
JA
National Centre for HIV Virology Research, Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, Frome Road, Adelaide 5000, Australia.
Carr
Jillian
J
Feng
Feng
F
Mundy
Linda
L
Burrell
Christopher
C
Li
Peng
P
D016346:Gene Products, vif / Q000235:genetics / Q000502:physiology*; D015658:HIV Infections / Q000209:etiology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009154:Mutation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051572:Proto-Oncogene Proteins c-hck; D012367:RNA, Viral / Q000378:metabolism; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D014746:Vimentin / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism; D019065:Virus Assembly; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus
D016346:Gene Products, vif; D011518:Proto-Oncogene Proteins; D012367:RNA, Viral; D014746:Vimentin; D014764:Viral Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D011505:Protein-Tyrosine Kinases; C496631:HCK protein, human; D051572:Proto-Oncogene Proteins c-hck