Nef Induces Multiple Genes Involved in Cholesterol Synthesis and Uptake in Human Immunodeficiency Virus Type 1-infected T Cells

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2005 Jul 15

PMID 16014965

Citations 60

Authors

Angelique B van t Wout

J Victor Swain

Michael Schindler

Ushnal Rao

Melissa S Pathmajeyan

James I Mullins

Frank Kirchhoff

Affiliations

Soon will be listed here.

Abstract

Several recent reports indicate that cholesterol might play an important role in human immunodeficiency virus type 1 (HIV-1) replication. We investigated the effects of HIV-1 infection on cholesterol biosynthesis and uptake using microarrays. HIV-1 increased gene expression of cholesterol genes in both transformed T-cell lines and primary CD4(+) T cells. Consistent with our microarray data, (14)C-labeled mevalonate and acetate incorporation was increased in HIV-1-infected cells. Our data also demonstrate that changes in cholesterol biosynthesis and uptake are only observed in the presence of functional Nef, suggesting that increased cholesterol synthesis may contribute to Nef-mediated enhancement of virion infectivity and viral replication.

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References

Chazal N, Gerlier D . Virus entry, assembly, budding, and membrane rafts. Microbiol Mol Biol Rev. 2003; 67(2):226-37, table of contents. PMC: 156468. DOI: 10.1128/MMBR.67.2.226-237.2003. View

Holm K, Weclewicz K, Hewson R, Suomalainen M . Human immunodeficiency virus type 1 assembly and lipid rafts: Pr55(gag) associates with membrane domains that are largely resistant to Brij98 but sensitive to Triton X-100. J Virol. 2003; 77(8):4805-17. PMC: 152122. DOI: 10.1128/jvi.77.8.4805-4817.2003. View

Schindler M, Wurfl S, Benaroch P, Greenough T, Daniels R, Easterbrook P . Down-modulation of mature major histocompatibility complex class II and up-regulation of invariant chain cell surface expression are well-conserved functions of human and simian immunodeficiency virus nef alleles. J Virol. 2003; 77(19):10548-56. PMC: 228419. DOI: 10.1128/jvi.77.19.10548-10556.2003. View

Popik W, Alce T . CD4 receptor localized to non-raft membrane microdomains supports HIV-1 entry. Identification of a novel raft localization marker in CD4. J Biol Chem. 2003; 279(1):704-12. DOI: 10.1074/jbc.M306380200. View

Sol-Foulon N, Esnault C, Percherancier Y, Porrot F, Metais-Cunha P, Bachelerie F . The effects of HIV-1 Nef on CD4 surface expression and viral infectivity in lymphoid cells are independent of rafts. J Biol Chem. 2004; 279(30):31398-408. DOI: 10.1074/jbc.M401621200. View

Del Real G, Jimenez-Baranda S, Mira E, Lacalle R, Lucas P, Gomez-Mouton C . Statins inhibit HIV-1 infection by down-regulating Rho activity. J Exp Med. 2004; 200(4):541-7. PMC: 2211926. DOI: 10.1084/jem.20040061. View

Aloia R, Tian H, JENSEN F . Lipid composition and fluidity of the human immunodeficiency virus envelope and host cell plasma membranes. Proc Natl Acad Sci U S A. 1993; 90(11):5181-5. PMC: 46679. DOI: 10.1073/pnas.90.11.5181. View

Maziere J, Landureau J, Giral P, Auclair M, Fall L, Lachgar A . Lovastatin inhibits HIV-1 expression in H9 human T lymphocytes cultured in cholesterol-poor medium. Biomed Pharmacother. 1994; 48(2):63-7. DOI: 10.1016/0753-3322(94)90077-9. View

Haughan P, Chance M, Goad L . Effects of an azasterol inhibitor of sterol 24-transmethylation on sterol biosynthesis and growth of Leishmania donovani promastigotes. Biochem J. 1995; 308 ( Pt 1):31-8. PMC: 1136839. DOI: 10.1042/bj3080031. View

10.

Rossio J, Esser M, Suryanarayana K, Schneider D, Bess Jr J, Vasquez G . Inactivation of human immunodeficiency virus type 1 infectivity with preservation of conformational and functional integrity of virion surface proteins. J Virol. 1998; 72(10):7992-8001. PMC: 110135. DOI: 10.1128/JVI.72.10.7992-8001.1998. View

11.

Folch J, Lees M, SLOANE STANLEY G . A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957; 226(1):497-509. View

12.

Nguyen D, Hildreth J . Evidence for budding of human immunodeficiency virus type 1 selectively from glycolipid-enriched membrane lipid rafts. J Virol. 2000; 74(7):3264-72. PMC: 111827. DOI: 10.1128/jvi.74.7.3264-3272.2000. View

13.

Rousso I, Mixon M, Chen B, Kim P . Palmitoylation of the HIV-1 envelope glycoprotein is critical for viral infectivity. Proc Natl Acad Sci U S A. 2000; 97(25):13523-5. PMC: 17608. DOI: 10.1073/pnas.240459697. View

14.

Manes S, del Real G, Lacalle R, Lucas P, Sanchez-Palomino S, Delgado R . Membrane raft microdomains mediate lateral assemblies required for HIV-1 infection. EMBO Rep. 2001; 1(2):190-6. PMC: 1084257. DOI: 10.1093/embo-reports/kvd025. View

15.

Lindwasser O, Resh M . Multimerization of human immunodeficiency virus type 1 Gag promotes its localization to barges, raft-like membrane microdomains. J Virol. 2001; 75(17):7913-24. PMC: 115035. DOI: 10.1128/jvi.75.17.7913-7924.2001. View

16.

Liao Z, Cimakasky L, Hampton R, Nguyen D, Hildreth J . Lipid rafts and HIV pathogenesis: host membrane cholesterol is required for infection by HIV type 1. AIDS Res Hum Retroviruses. 2001; 17(11):1009-19. DOI: 10.1089/088922201300343690. View

17.

Ono A, Freed E . Plasma membrane rafts play a critical role in HIV-1 assembly and release. Proc Natl Acad Sci U S A. 2001; 98(24):13925-30. PMC: 61143. DOI: 10.1073/pnas.241320298. View

18.

Horton J, Goldstein J, Brown M . SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 2002; 109(9):1125-31. PMC: 150968. DOI: 10.1172/JCI15593. View

19.

Guyader M, Kiyokawa E, Abrami L, Turelli P, Trono D . Role for human immunodeficiency virus type 1 membrane cholesterol in viral internalization. J Virol. 2002; 76(20):10356-64. PMC: 136590. DOI: 10.1128/jvi.76.20.10356-10364.2002. View

20.

van t Wout A, Lehrman G, Mikheeva S, OKeeffe G, Katze M, Bumgarner R . Cellular gene expression upon human immunodeficiency virus type 1 infection of CD4(+)-T-cell lines. J Virol. 2002; 77(2):1392-402. PMC: 140827. DOI: 10.1128/jvi.77.2.1392-1402.2003. View