Diminished production of human immunodeficiency virus type 1 in astrocytesresults from inefficient translation of gag, env, and nef mRNAs despite efficient expression of Tat and Rev

Astrocytes infected with human immunodeficiency virus type 1 (HIV-1) produc e only minimal quantities of virus. The molecular events that limit acute-p hase HIV-1 infection of astrocytes were examined after inducing acute-phase replication by transfection with the pNL4-3 proviral plasmid. The levels o f HIV-1 mRNA were similarly high in both astrocytes and HeLa cells, but ast rocytes produced approximately 50-fold less supernatant p24 than HeLa cells . We found that diminished HIV-1 production in astrocytes resulted from ine fficient translation of gag, env, and nef mRNAs that were efficiently trans ported to the cytoplasm. Tat- or Rev-dependent reporter constructs showed n o 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 efficie ntly translated from their native mRNAs. Pulse-chase labelling and immunobl ot experiments revealed no defect in protein processing, but levels of Gag, Env, or Nef protein expressed were dramatically reduced in astrocytes comp ared to HeLa cells. These results demonstrate that inefficient translation of HIV-1 structural proteins underlies the restricted infection of astrocyt es. The efficient expression of functional Tat and Rev by astrocytes may co ntribute to HIV-1 neuropathogenesis.