G2 Cell Cycle Arrest and Cyclophilin A in Lentiviral Gene Transfer

Shangming Zhang, Guiandre Joseph, Karen Pollok, Lionel Berthoux, Lakshmi Sastry, Jeremy Luban, Kenneth Cornetta

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Lentiviral vectors derived from the human immunodeficiency virus-1 (HIV-1) have a higher propensity to transduce nondividing cells compared to vectors based on oncoretroviruses. We report here that genistein, a previously known protein tyrosine kinase (PTK) inhibitor and G2 cell cycle arrest inducer, significantly enhanced lentiviral transduction in a dose-dependent manner. Increased transduction, as measured by vector expression, was seen in a variety of human cell lines, murine primary lymphocytes, and primary human CD34+ peripheral blood progenitor cells as well. Increased vector expression was also associated with an increase in vector DNA copy number, as assessed by quantitative PCR. Genistein-mediated G2 cell cycle arrest, rather than PTK inhibition, appears to be the major factor responsible for increased gene transfer. Genistein also increases cyclophilin A (CypA) protein, a cellular protein important for efficient HIV-1 infection. While we show that CypA-/- Jurkat cells transduce poorly with lentiviral vectors, genistein does increase gene transfer in CypA-deficient cells. CypA and G2 cell cycle arrest appear to be two independent factors important for efficient lentiviral gene transfer. The role of genistein and other G2-arresting agents may be useful for improving the efficiency of lentiviral gene therapy.

Original languageEnglish
Pages (from-to)546-554
Number of pages9
JournalMolecular Therapy
Volume14
Issue number4
DOIs
StatePublished - Oct 2006

Fingerprint

Cyclophilin A
G2 Phase Cell Cycle Checkpoints
Genistein
Genes
Protein-Tyrosine Kinases
HIV-1
Jurkat Cells
Virus Diseases
Protein Kinase Inhibitors
Genetic Therapy
Blood Cells
Proteins
Stem Cells
Lymphocytes
Cell Line
Polymerase Chain Reaction
DNA

Keywords

  • cyclophilin A
  • cyclosporin A
  • gene therapy
  • genistein
  • human immunodeficiency virus-1
  • lentiviral vector
  • vesicular stomatitis virus glycoprotein

ASJC Scopus subject areas

  • Molecular Biology

Cite this

G2 Cell Cycle Arrest and Cyclophilin A in Lentiviral Gene Transfer. / Zhang, Shangming; Joseph, Guiandre; Pollok, Karen; Berthoux, Lionel; Sastry, Lakshmi; Luban, Jeremy; Cornetta, Kenneth.

In: Molecular Therapy, Vol. 14, No. 4, 10.2006, p. 546-554.

Research output: Contribution to journalArticle

Zhang, Shangming ; Joseph, Guiandre ; Pollok, Karen ; Berthoux, Lionel ; Sastry, Lakshmi ; Luban, Jeremy ; Cornetta, Kenneth. / G2 Cell Cycle Arrest and Cyclophilin A in Lentiviral Gene Transfer. In: Molecular Therapy. 2006 ; Vol. 14, No. 4. pp. 546-554.
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