Aberrant, noninfectious HIV-1 particles are released by chronically infected human T cells transduced with a retroviral vector expressing an interfering HIV-1 variant

Abstract

The expression of the nonproducer F12-HIV-1 genome has been previously shown to protect the host cell from HIV superinfection. In order to estimate the efficacy of the F12-HIV genome as an anti-HIV reagent also in cells already infected, an HIV-1 chronically infected Hut-78 cell clone (D10) was superinfected with an amphotropic mouse/human pseudotype retrovirus whose genome expresses both the F12-HIV genome and the selection marker gene (ie the c-DNA of a truncated form of the nerve growth factor receptor, NGFr) under the control of F12-HIV 5′LTR. D10 cells homogenously expressing the F12-HIV genome (T-D10) released unaltered amounts of retrovirions whose infectivity was, however, dramatically impaired (from 9 × 10³ in D10 to <10^0.5 TCID₅₀/ml in T-D10 super- natants). Electron microscopy showed that the morphology of retrovirions released by T-D10 cells was heavily altered, both in size and shape. Furthermore, no retrotranscription products were detectable in CD4⁺ cells challenged with T-D10 retrovirions. For the first time, the block in the infectivity of HIV released from already infected cells through the expression of an anti-HIV retroviral vector was demonstrated. These data could have important implications both from a perspective of F12-HIV-based anti-HIV gene therapy and, in general, on the role that nonproducer and/or defective HIV could play ‘in vivo’ in HIV infection and AIDS pathogenesis.