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

R. Bona, P. D'Aloja, E. Olivetta, A. Modesti, A. Modica, A. Geraci, G. Ferrari, P. Verani, M. Federico

Research output: Contribution to journalArticle

Abstract

The expression of the nonproducer F-12-HIV-1 genome has been previously shown to protect the host cell from HIV superinfection. In order to estimate the efficacy of F-12-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 x 103 in D10 to <100.5 TCID50/ml in T-D10 supernatants). 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.

Original languageEnglish
Pages (from-to)1085-1092
Number of pages8
JournalGene Therapy
Volume4
Issue number10
Publication statusPublished - 1997

Keywords

  • anti-HIV gene therapy
  • Nonproducer HIV-1 variant
  • Retroviral vector

ASJC Scopus subject areas

  • Genetics

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    Bona, R., D'Aloja, P., Olivetta, E., Modesti, A., Modica, A., Geraci, A., Ferrari, G., Verani, P., & Federico, M. (1997). Aberrant, noninfectious HIV-1 particles are released by chronically infected human T cells transduced with a retroviral vector expressing an interfering HIV-1 Variant. Gene Therapy, 4(10), 1085-1092.