Cellular motor protein KIF-4 associates with retroviral Gag

Previously we demonstrated that murine retroviral Gag proteins associate wi th a cellular motor protein, I(KIF-4. Using the yeast two-hybrid assay, we also found an association of KIF-4 with Gag proteins of Mason-Pfizer monkey virus (MPMV). simian immunodeficiency virus (SIV), and human immunodeficie ncy virus type 1 (HIV-1), Studies performed with mammalian fell systems con firmed that the HIV-1 Gag protein associates with KIF-4. Soluble cytoplasmi c proteins from cells infected with recombinant vaccinia virus expressing t he entire Gag-Pol precursor protein of HIV-1 or transfected with HIV-1 mole cular clone pNL4-3 were fractionated by sucrose gradient centrifugation and further separated by size-exclusion and anion-exchange chromatographies, K IF-4 and HIV-1 Gag cofractionated in both chromatographic separations, Immu noprecipitation assays have also verified the KIF-4-Gag association. KIF-4 binds mainly to the Gag precursor (Pr55 Gag) and a matrix-capsid processing intermediate (Pr42) but not to other processed Gag products. The binding o f Gag is mediated hy a domain of KIF-4 proximal to the C terminus. These re sults, and our previous studies, raise the possibility that KIF-4 may play an important role in retrovirus Gag protein transport.