HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 9, 8553-8563, March 4, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/9/8553    most recent M407863200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rajendra Kumar, P. Articles by Mahalingam, S. Search for Related Content PubMed PubMed Citation Articles by Rajendra Kumar, P. Articles by Mahalingam, S. Social Bookmarking                      What's this?

Phosphorylation by MAPK Regulates Simian Immunodeficiency Virus Vpx Protein Nuclear Import and Virus Infectivity^*

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

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

Transport of the viral genome into the nucleus required phosphorylation of components in the preintegration complex by virion-associated host cellular kinases. In this study, we showed that ERK-2/MAPK is associated with simian immunodeficiency virus (SIV) virions and regulated the nuclear transport of Vpx and virus replication in non-proliferating target cells by phosphorylating Vpx. Suppression of the virion-associated ERK-2 activity by MAPK pathway inhibitors impaired both Vpx nuclear import and viral infectivity without affecting virus particle maturation and release. In addition, mutation analysis indicated that the inactivation of Vpx phosphorylation precluded nuclear import and reduced virus replication in macrophage cultures, even when functional integrase and Gag matrix proteins implicated in viral preintegration complex nuclear import are present. In this study, we also showed that co-localization of Vpx with Gag precursor in the cytoplasm is a prerequisite for Vpx incorporation into virus particles. Substitution of hydrophobic Leu-74 and Ile-75 with serines in the helical domain abrogated Vpx nuclear import, and its incorporation into virus particles, despite its localization in the cytoplasm, suggested that the structural integrity of helical domains is critical for Vpx functions. Taken together, these studies demonstrated that the host cell MAPK signal transduction pathway regulated an early step in SIV infection.

Received for publication, July 13, 2004 , and in revised form, November 18, 2004.

^* This work was supported by a grant from Department of Biotechnology, Government of India (to S. M.), core support from the Department of Biotechnology and Centre for DNA Fingerprinting and Diagnostics, and by graduate fellowships from Council of Scientific and Industrial Research, Government of India (to P. R. K., P. K. S., and M. R. K. S. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Laboratory of Molecular Virology, Centre for DNA Fingerprinting and Diagnostics, ECIL Rd., Nacharam, Hyderabad 500 076, India. Tel.: 11-91-40-27171478; Fax: 11-91-40-27155610; E-mail: maha{at}cdfd.org.in.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Goujon, V. Arfi, T. Pertel, J. Luban, J. Lienard, D. Rigal, J.-L. Darlix, and A. Cimarelli Characterization of Simian Immunodeficiency Virus SIVSM/Human Immunodeficiency Virus Type 2 Vpx Function in Human Myeloid Cells J. Virol., December 15, 2008; 82(24): 12335 - 12345. [Abstract] [Full Text] [PDF]

				P. K. Singhal, P. Rajendra Kumar, M. R. K. Subba Rao, and S. Mahalingam Nuclear Export of Simian Immunodeficiency Virus Vpx Protein J. Virol., December 15, 2006; 80(24): 12271 - 12282. [Abstract] [Full Text] [PDF]

				P. K. Singhal, P. R. Kumar, M. R. K. S. Rao, M. Kyasani, and S. Mahalingam Simian Immunodeficiency Virus Vpx Is Imported into the Nucleus via Importin Alpha-Dependent and -Independent Pathways J. Virol., January 1, 2006; 80(1): 526 - 536. [Abstract] [Full Text] [PDF]