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Journal of Virology, November 2008, p. 11228-11238, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.00981-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Retroviruses Human Immunodeficiency Virus and Murine Leukemia Virus Are Enriched in Phosphoinositides ^,

Robin Chan,¹ Pradeep D. Uchil,³ Jing Jin,³ Guanghou Shui,¹ David E. Ott,^4, Walther Mothes,^3, and Markus R. Wenk^1,2,*

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore,¹ Department of Biological Sciences, National University of Singapore, Singapore, Singapore,² Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut,³ SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, Maryland⁴

Received 12 May 2008/ Accepted 28 August 2008

Retroviruses acquire a lipid envelope during budding from the membrane of their hosts. Therefore, the composition of this envelope can provide important information about the budding process and its location. Here, we present mass spectrometry analysis of the lipid content of human immunodeficiency virus type 1 (HIV-1) and murine leukemia virus (MLV). The results of this comprehensive survey found that the overall lipid content of these viruses mostly matched that of the plasma membrane, which was considerably different from the total lipid content of the cells. However, several lipids are enriched in comparison to the composition of the plasma membrane: (i) cholesterol, ceramide, and GM3; and (ii) phosphoinositides, phosphorylated derivatives of phosphatidylinositol. Interestingly, microvesicles, which are similar in size to viruses and are also released from the cell periphery, lack phosphoinositides, suggesting a different budding mechanism/location for these particles than for retroviruses. One phosphoinositide, phosphatidylinositol 4,5-bisphosphate [PI(4,5)P₂], has been implicated in membrane binding by HIV Gag. Consistent with this observation, we found that PI(4,5)P₂ was enriched in HIV-1 and that depleting this molecule in cells reduced HIV-1 budding. Analysis of mutant virions mapped the enrichment of PI(4,5)P₂ to the matrix domain of HIV Gag. Overall, these results suggest that HIV-1 and other retroviruses bud from cholesterol-rich regions of the plasma membrane and exploit matrix/PI(4,5)P₂ interactions for particle release from cells.

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* Corresponding author. Mailing address: Centre for Life Sciences (CeLS), Yong Loo Lin School of Medicine, National University of Singapore, 28 Medical Drive, Level 04-21, Singapore 117607, Singapore. Phone: 65 6516 3624. Fax: 65 6777 3271. E-mail: bchmrw{at}nus.edu.sg

Published ahead of print on 17 September 2008.

Supplemental material for this article may be found at http://jvi.asm.org/.

D.E.O., W.M., and M.R.W. are co-senior authors of the paper.

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Journal of Virology, November 2008, p. 11228-11238, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.00981-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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