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.

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

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.

Hum Gene Ther. 1998 Mar 1;9(4):487-96. Unique Identifier : AIDSLINE MED/98184222
Poznansky MC; Foxall R; Mhashilkar A; Coker R; Jones S; Ramstedt U; Marasco W; The Dept. of Genito-Urinary Medicine and Communicable Diseases,; Imperial College School of Medicine at St. Mary's, London, UK.

Abstract: 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 m10 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-Ckappa). 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.

Keywords: *CD4-Positive T-Lymphocytes/VIROLOGY *Gene Products, tat/IMMUNOLOGY *HIV Antibodies/IMMUNOLOGY *HIV Envelope Protein gp120/IMMUNOLOGY *HIV-1/PHYSIOLOGY *Virus Replication/IMMUNOLOGY

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