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Journal of Virology, December 2006, p. 12271-12282, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.00563-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Nuclear Export of Simian Immunodeficiency Virus Vpx Protein{triangledown}

Prabhat K. Singhal, P. Rajendra Kumar, Malireddi R. K. Subba Rao, and Sundarasamy Mahalingam*

Laboratory of Molecular Virology, Centre for DNA Fingerprinting and Diagnostics, ECIL Road, Hyderabad 500 076, India

Received 17 March 2006/ Accepted 6 September 2006

Lentiviruses, human immunodeficiency viruses (HIVs), and simian immunodeficiency viruses (SIVs) are distinguished from oncoretroviruses by their ability to infect nondividing cells such as macrophages. Retroviruses must gain access to the host cell nucleus for replication and propagation. HIV and SIV preintegration complexes (PIC) enter nuclei after traversing the central aqueous channel of the limiting nuclear pore complex without membrane breakdown. Among the nucleophilic proteins, namely, matrix, integrase, Vpx, and Vpr, present in HIV type 2/SIV PIC, Vpx is implicated in nuclear targeting and is also available for incorporation into budding virions at the plasma membrane. The mechanisms of these two opposite functions are not known. We demonstrate that Vpx is a nucleocytoplasmic shuttling protein and contains two novel noncanonical nuclear import signals and a leptomycin B-sensitive nuclear export signal. In addition, Vpx interacts with the cellular tyrosine kinase Fyn through its C-terminal proline-rich motif. Furthermore, our data indicate that Fyn kinase phosphorylates Vpx and regulates its export from nucleus. Replacement of conserved tryptophan residues within domain 41 to 63 and tyrosine residues at positions 66, 69, and 71 in Vpx impairs its nuclear export, virion incorporation, and SIV replication in macrophages. Nuclear export is essential to ensure the availability of Vpx in the cytoplasm for incorporation into virions, leading to efficient viral replication within nondividing cells.

* Corresponding author. Mailing address: Laboratory of Molecular Virology, Centre for DNA Fingerprinting and Diagnostics (CDFD), ECIL Road, Nacharam, Hyderabad 500 076, India. Phone: (91-40)-27171478. Fax: (91-40)-27155610. E-mail: maha{at}cdfd.org.in.

{triangledown} Published ahead of print on 20 September 2006.

Journal of Virology, December 2006, p. 12271-12282, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.00563-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Goujon, C., Arfi, V., Pertel, T., Luban, J., Lienard, J., Rigal, D., Darlix, J.-L., Cimarelli, A. (2008). Characterization of Simian Immunodeficiency Virus SIVSM/Human Immunodeficiency Virus Type 2 Vpx Function in Human Myeloid Cells. J. Virol. 82: 12335-12345 [Abstract] [Full Text]  


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