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Journal of Virology, December 1999, p. 10508-10513, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Cellular Motor Protein KIF-4 Associates with Retroviral Gag

Yao Tang,1 Ulrike Winkler,1 Eric O. Freed,2 Ted A. Torrey,1 Wankee Kim,3 Henry Li,4 Stephen P. Goff,4 and Herbert C. Morse III1,*

Laboratory of Immunopathology1 and Laboratory of Molecular Microbiology,2 National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; Institute for Medical Science, School of Medicine, Ajou University, Suwon, Korea3; and Department of Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, New York, New York4

Received 26 March 1999/Accepted 24 August 1999

Previously we demonstrated that murine retroviral Gag proteins associate with a cellular motor protein, 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 immunodeficiency virus type 1 (HIV-1). Studies performed with mammalian cell systems confirmed that the HIV-1 Gag protein associates with KIF-4. Soluble cytoplasmic proteins from cells infected with recombinant vaccinia virus expressing the entire Gag-Pol precursor protein of HIV-1 or transfected with HIV-1 molecular clone pNL4-3 were fractionated by sucrose gradient centrifugation and further separated by size-exclusion and anion-exchange chromatographies. KIF-4 and HIV-1 Gag cofractionated in both chromatographic separations. Immunoprecipitation 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 of Gag is mediated by a domain of KIF-4 proximal to the C terminus. These results, and our previous studies, raise the possibility that KIF-4 may play an important role in retrovirus Gag protein transport.

* Corresponding author. Mailing address: LIP, NIAID, NIH, Building 7, Room 304, MSC 0760, Bethesda, MD 20892-0760. Phone: (301) 496-6379. Fax: (301) 402-0077. E-mail: hm16c{at}nih.gov.

Journal of Virology, December 1999, p. 10508-10513, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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