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Journal of Virology, January 1999, p. 352-361, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Diminished Production of Human Immunodeficiency Virus Type 1 in Astrocytes Results from Inefficient Translation of gag, env, and nef mRNAs despite Efficient Expression of Tat and Rev

Paul R. Gorry,1,2 Jane L. Howard,1 Melissa J. Churchill,3,5 Jenny L. Anderson,1,3 Anthony Cunningham,4,5 Deborah Adrian,4,5 Dale A. McPhee,1,5 and Damian F. J. Purcell1,*

AIDS Cellular1 and Molecular3Biology Units, Macfarlane Burnet Centre for Medical Research, Fairfield 3078, and Department of Medical Laboratory Science, RMIT University, Melbourne 3001,2 Victoria, Centre for Virus Research, Westmead Institutes of Health Research, Westmead Hospital, University of Sydney, Westmead 2145, New South Wales,4 and National Centre in HIV Virology Research, Fairfield 3078, Victoria,5 Australia

Received 18 May 1998/Accepted 14 October 1998

Astrocytes infected with human immunodeficiency virus type 1 (HIV-1) produce only minimal quantities of virus. The molecular events that limit acute-phase HIV-1 infection of astrocytes were examined after inducing acute-phase replication by transfection with the pNL4-3 proviral plasmid. The levels of HIV-1 mRNA were similarly high in both astrocytes and HeLa cells, but astrocytes produced approximately 50-fold less supernatant p24 than HeLa cells. We found that diminished HIV-1 production in astrocytes resulted from inefficient translation of gag, env, and nef mRNAs that were efficiently transported to the cytoplasm. Tat- or Rev-dependent reporter constructs showed no defect in Tat or Rev function in astrocytes compared with HeLa cells. HIV-1 mRNAs were correctly spliced, but only Rev and Tat proteins were efficiently translated from their native mRNAs. Pulse-chase labelling and immunoblot experiments revealed no defect in protein processing, but levels of Gag, Env, or Nef protein expressed were dramatically reduced in astrocytes compared to HeLa cells. These results demonstrate that inefficient translation of HIV-1 structural proteins underlies the restricted infection of astrocytes. The efficient expression of functional Tat and Rev by astrocytes may contribute to HIV-1 neuropathogenesis.

* Corresponding author. Mailing address: Macfarlane Burnet Centre for Medical Research, P.O. Box 254, Fairfield, Victoria 3078, Australia. Phone: 61-3-9282-2256. Fax: 61-3-9282-2100. E-mail: purcell{at}burnet.edu.au.

Journal of Virology, January 1999, p. 352-361, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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