17Mar 2020

THE ROLE OF MOTOR PROTEIN KIF4 DURING VIRAL INFECTION AND ITS CLINICAL POTENTIAL

  • Institute of Pathological Sciences, Department of Medical Microbiology, Laboratory of Molecular Virology, Semmelweis University - Nagyvaradter 4, 1086, Budapest, Hungary.
  • Immunology Department, EotvosLorand University - Pazmany Peterstny. 1, 1117, Budapest, Hungary.
  • Clinical Experimental Research Institute, Department of Translational Medicine, Semmelweis University - Tuzolto u. 37-47, 1094, Budapest, Hungary.
  • Abstract
  • Keywords
  • References
  • Cite This Article as
  • Corresponding Author

Kinesin and dynein are two types of ATP-dependent mechanochemical motors that are involved in the transport of a variety of cytoplasmic cargos along microtubule fibers, the regulation of microtubule stability and the maintenance of centrosome integrity. Besides being responsible for both the maintenance of cell morphology and physiological functions, kinesins also play important roles in cell division, cell motility, spindle assembly, chromosome aggregation and separation. Although its role might be different in different types of cancer, some KIFS have been known to play a role in many types of cancer development, and they have also been pointed as interacting with viruses during viral infection, notably during viral egress. With an ongoing need for novel anti-retroviral treatments, these findings open the way for further studies with this motor protein, aiming the development of new and more efficient treatment strategies for chronic diseases such as AIDS caused by these fast-mutating viruses. This article presents an overview of KIF4 structure and functions and focus on its interactions with the Gag retroviral polyprotein during retroviral infection. Moreover, we draw attention to KIFs clinical potential as a therapeutic target to block retroviral infections by interfering with the production of new viral particles through microtubules destabilization.


  1. Camlin, N. J., McLaughlin, E. A. and Holt, J. E. (2017) ?Kif4 Is Essential for Mouse Oocyte Meiosis, PLOS ONE. Public Library of Science, 12(1), p. e0170650. Available at: https://doi.org/10.1371/journal.pone.0170650.
  2. Chang, Q. et al. (2013) ?Structural basis for the ATP-induced isomerization of kinesin, Journal of Molecular Biology. Elsevier Ltd, 425(11), pp. 1869?1880. doi: 10.1016/j.jmb.2013.03.004.
  3. Cochrane, A. W., Mcnally, M. T. and Mouland, A. J. (2006) ?The retrovirus RNA trafficking granule: from birth to maturity, Retrovirology, 18(3). doi: 10.1186/1742-4690-3-18.
  4. Coffin, J. M., Hughes, S. H. and Varmus, H. E. (eds) (1997) Retroviruses. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press. Available at: https://www.ncbi.nlm.nih.gov/books/NBK19376/.
  5. Elsner, C. and Bohne, J. (2017) ?The retroviral vector family: something for everyone, Virus Genes. Springer US, 53(5), pp. 714?722. doi: 10.1007/s11262-017-1489-0.
  6. Gao, J. et al. (2011) ?Overexpression of chromokinesin KIF4 inhibits proliferation of human gastric carcinoma cells both in vitro and in vivo, Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 32(1), p. 53?61. doi: 10.1007/s13277-010-0090-0.
  7. Gifford, R. and Tristem, M. (2003) ?The Evolution, Distribution and Diversity of Endogenous Retroviruses*, 26(3), pp. 291?315.
  8. Hu, C. K. et al. (2011) ?KIF4 regulates midzone length during cytokinesis, Current Biology. Elsevier Ltd, 21(10), pp. 815?824. doi: 10.1016/j.cub.2011.04.019.
  9. Kim, W. et al. (1998) ?Binding of murine leukemia virus Gag polyproteins to KIF4, a microtubule-based motor protein, Journal of Virology, 72(8), pp. 6898?6901. Available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9658142%5Cnpapers2://publication/uuid/44D0AE5D-E51C-43B1-AACF-CE3563524548.
  10. Kolomeisky, A. B. (2013) ?Motor proteins and molecular motors: How to operate machines at the nanoscale, Journal of Physics Condensed Matter, 25(46). doi: 10.1088/0953-8984/25/46/463101.
  11. Lee, Y. M. et al. (2001) ?Human kinesin superfamily member 4 is dominantly localized in the nuclear matrix and is associated with chromosomes during mitosis., The Biochemical journal, 360(Pt 3), pp. 549?56. doi: 10.1042/bj3600549.
  12. Martinez, N. W. et al. (2008) ?Kinesin KIF4 Regulates Intracellular Trafficking and Stability of the Human Immunodeficiency Virus Type 1 Gag Polyprotein, Journal of Virology, 82(20), pp. 9937?9950. doi: 10.1128/JVI.00819-08.
  13. Matsumoto, Y. et al. (2018) ?Enhanced expression of KIF4A in colorectal cancer is associated with lymph node metastasis, Oncology letters. 2017/12/08. D.A. Spandidos, 15(2), pp. 2188?2194. doi: 10.3892/ol.2017.7555.
  14. Miki, H. and Hirokawa, N. (2013) ?Kinesin Superfamily Classification, in Roberts, G. C. K. (ed.) Encyclopedia of Biophysics. Berlin, Heidelberg: Springer Berlin Heidelberg, pp. 1191?1200. doi: 10.1007/978-3-642-16712-6_762.
  15. Miki, H., Okada, Y. and Hirokawa, N. (2005) ?Analysis of the kinesin superfamily: Insights into structure and function, Trends in Cell Biology, 15(9), pp. 467?476. doi: 10.1016/j.tcb.2005.07.006.
  16. Morris, E. J. et al. (2014) ?Kif4 Interacts with EB1 and Stabilizes Microtubules Downstream of Rho-mDia in Migrating Fibroblasts, 9(3). doi: 10.1371/journal.pone.0091568.
  17. Naghavi, M. H. et al. (2007) ?Moesin regulates stable microtubule formation and limits retroviral infection in cultured cells, (November 2006), pp. 41?52. doi: 10.1038/sj.emboj.7601475.
  18. Naghavi, M. H. and Walsh, D. (2017) ?Microtubule Regulation and Function during Virus Infection, Journal of Virology, 91(16), pp. e00538-17. doi: 10.1128/JVI.00538-17.
  19. Nelson, E. E. and Guyer, A. E. (2012) ?The Taking of the Cytoskeleton One Two Three: How Viruses Utilize the Cytoskeleton During Egress, 1(3), pp. 233?245. doi: 10.1016/j.dcn.2011.01.002.The.
  20. Nunes Bastos, R. et al.(2013) ?Aurora B suppresses microtubule dynamics and limits central spindle size by locally activating KIF4A, The Journal of cell biology. 2013/08/12. The Rockefeller University Press, 202(4), pp. 605?621. doi: 10.1083/jcb.201301094.
  21. Ono, A. and Freed, E. O. (1999) ?Binding of Human Immunodeficiency Virus Type 1 Gag to Membrane: Role of the Matrix Amino Terminus, Aids Research, 73(5), pp. 4136?4144.
  22. Radtke, K., Dohner, K. and Sodeik, B. (2006) ?Viral interactions with the cytoskeleton: a hitchhikers guide to the cell, Cellular Microbiology, 8(3), pp. 387?400. doi: 10.1111/j.1462-5822.2005.00679.x.
  23. Sabo, Y. et al. (2013) ?HIV-1 induces the formation of stable microtubules to enhance early infection, Cell Host and Microbe. Elsevier Inc., 14(5), pp. 535?546. doi: 10.1016/j.chom.2013.10.012.
  24. Samejima, K. et al. (2012) ?Mitotic chromosomes are compacted laterally by KIF4 and condensin and axially by topoisomerase IIα, The Journal of cell biology. 2012/11/19. The Rockefeller University Press, 199(5), pp. 755?770. doi: 10.1083/jcb.201202155.
  25. Sekine, Y. et al. (1994) ?A novel microtubule-based motor protein (KIF4) for organelle transports, whose expression is regulated developmentally, Journal of Cell Biology, 127(1), pp. 187?201. doi: 10.1083/jcb.127.1.187.
  26. Sheng, L. et al. (2018a) ?The multiple functions of kinesin-4 family motor protein KIF4 and its clinical potential, Gene. Elsevier, 678(June), pp. 90?99. doi: 10.1016/j.gene.2018.08.005.
  27. Sheng, L. et al. (2018b) ?The multiple functions of kinesin-4 family motor protein KIF4 and its clinical potential, Gene. Elsevier B.V, 678, pp. 90?99. doi: 10.1016/j.gene.2018.08.005.
  28. Shrestha, S. et al. (2012) ?PRC1 controls spindle polarization and recruitment of cytokinetic factors during monopolar cytokinesis, Molecular Biology of the Cell, 23(7), pp. 1196?1207. doi: 10.1091/mbc.E11-12-1008.
  29. Sodeik, K. D. B. (2004) ?The Role of the Cytoskeleton During Viral Infection, pp. 67?108.
  30. Tang, Y. et al. (1999) ?Cellular motor protein KIF-4 associates with retroviral Gag., Journal of Virology, 73(12), pp. 10508?10513.
  31. Tiwari, N. et al. (2013) ?Klf4 Is a Transcriptional Regulator of Genes Critical for EMT, Including Jnk1 (Mapk8), PLoS ONE, 8(2). doi: 10.1371/journal.pone.0057329.
  32. Voets, E. et al. (2015) ?The lethal response to Cdk1 inhibition depends on sister chromatid alignment errors generated by KIF4 and isoform 1 of PRC1, Scientific reports. Nature Publishing Group, 5, p. 14798. doi: 10.1038/srep14798.
  33. Wu, G. et al. (2008) ?A novel role of the chromokinesin Kif4A in DNA damage response, Cell Cycle, 7(13), pp. 2013?2020. doi: 10.4161/cc.7.13.6130.
  34. Yuan, X. I. N. et al. (1993) ?Mutations in the N-terminal region of human immunodeficiency virus type 1 matrix protein block intracellular transport of the Gag precursor, Virol., 67(11), pp. 6387-6394.
  35. Zhou, J. et al. (2018) ?Role of kinesins in directed adenovirus transport and cytoplasmic exploration, PLoS Pathogens, 14(5), pp. 1?22. doi: 10.1371/journal.ppat.1007055.
  36. Zhou, W. et al. (1994) ?Identification of a membrane-binding domain within the amino-terminal region of human immunodeficiency virus type 1 Gag protein which interacts with acidic phospholipids., Journal of virology, 68(4), pp. 2556?69. doi: 10.1016/J.AB.2013.02.011.
  37. Zhu, C. and Jiang, W. (2005) ?Cell cycle-dependent translocation of PRC1 on the spindle by Kif4 is essential for midzone formation and cytokinesis, Proceedings of the National Academy of Sciences, 102(2), pp. 343?348. doi: 10.1109/TPDS.2006.94.

[Priscilla Gomes Da Silva, Hani Hashim Hammad and Pedro Henrique Leroy Viana (2020); THE ROLE OF MOTOR PROTEIN KIF4 DURING VIRAL INFECTION AND ITS CLINICAL POTENTIAL Int. J. of Adv. Res. 8 (Mar). 109-115] (ISSN 2320-5407). www.journalijar.com


Priscilla Gomes da Silva
Institute of Pathological Sciences, Department of Medical Microbiology, Laboratory of Molecular Virology, Semmelweis University

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