Inhibition of human immunodeficiency virus replication and growth advantage of CD4+ T cells from HIV-infected individuals that express intracellular antibodies against HIV-1 gp120 or tat

Current clinical gene therapy protocols for the treatment of human immunodeficiency virus type 1 (HIV-1) infection often involve the ex vivo transduction and expansion of CD4(+) T cells derived from HIV-positive patients at a late stage in their disease (CD4 count <400), These protocols involve the transduction of T cells by murine leukemia virus (MLV)-based vectors encoding antiviral constructs such as the rev mill dominant negative mutant or a ribozyme directed against the CAP site of HIV-1 RNA, We examined the efficiency and stability of transduction of CD4(+) T cells derived from HIV-infected patients at different stages in the progression of their disease, from seroconversion to AIDS, CD4(+) T cells from HIV-positive patients and uninfected donors were transduced with MLV-based vectors encoding beta-galactosidase and an intracellular antibody directed against gp120 (sFv 105) or Tat, (sFvtat1-C-kappa). The expression of marker genes and the effects of the antiviral constructs were monitored in vitro in unselected transduced CD4(+) T cells, Efficiency and stability of transduction varied during the course of HIV infection; CD4(+) T cells derived from asymptomatic patients were transducible at higher efficiencies and stabilities than CD4(+) T cells from patients with acquired immunodeficiency syndrome (AIDS), Expression of the anti-tat intracellular antibody was more effective at stably inhibiting HIV-1 replication in transduced cells from HIV-infected individuals than was sFv 105, The results of this study have important implications for the development of a clinically relevant gene therapy for the treatment of HIV-1 infection.