Inhibition of HIV replication: a powerful antiviral strategy by IFN-beta gene delivery in CD4+ cells

Biochem Pharmacol. 2007 Sep 15;74(6):898-910. doi: 10.1016/j.bcp.2007.06.036. Epub 2007 Jun 27.

Abstract

In this study, we demonstrated the efficiency and feasibility of a gene therapy protocol against HIV infection using the antiviral effects of IFN-beta expression. Lentiviral vectors containing the human or the simian IFN-beta sequences under the influence of the murine moderate H2-kb promoter were constructed. To examine the capacity of IFN-beta to inhibit the replication of HIV in human CD4(+) cells, a transduction protocol permitting to efficiently transduce CD4(+) cells or PBMC (85+/-12% of CD4(+)-transduced cells) with a moderate expression of IFN-beta was developed. Results indicate that enforced expression of IFN-beta has no negative effects in terms of apoptosis and proliferation. In human CD4(+) cells, it drastically inhibits (up to 99.9%) replication after challenging with different strains of HIV-1. The expression of exogenous IFN-beta leads to an amplification of the CD4(+) cells (11-fold) and to a drastic decrease of the p24 protein. Micro-array analyses indicated that antiviral effect of IFN-beta could be due to a major regulation of the inflammatory response. These results are encouraging for the development of a clinical study of gene therapy against AIDS using IFN-beta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / pharmacology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / transplantation
  • Cell Proliferation / drug effects
  • Genetic Therapy / methods*
  • Genetic Vectors
  • HIV Infections / therapy*
  • HIV-1 / drug effects*
  • Haplorhini
  • Humans
  • Inflammation / drug therapy
  • Interferon-beta / administration & dosage*
  • Interferon-beta / pharmacology
  • Mice
  • Transduction, Genetic
  • Virus Replication / drug effects*

Substances

  • Antiviral Agents
  • Interferon-beta