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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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