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Highly Efficient Transfection of Human THP-1 Macrophages by Nucleofection
Published on: September 2, 2014
Transduction of nondividing human macrophages with gammaretrovirus-derived vectors
Loraine Jarrosson-Wuilleme1, Caroline Goujon, Jeanine Bernaud
1LaboRetro, INSERM U412, Ecole Normale Supérieure de Lyon, IFR 128 BioSciences Lyon-Gerland, 46 Allée d'Italie, 69364 Lyon, France.
Abstract:
It is commonly accepted that infection of nondividing cells by gammaretroviruses such as the murine leukemia viruses is inefficient due to their inability to cross the nuclear envelope barrier. Challenging this notion, we now show that human nondividing macrophages display a specific window of susceptibility to transduction with a Friend murine leukemia virus (F-MLV)-derived vector during their differentiation from monocytes. This finding suggests that factors other than the nuclear membrane govern permissiveness to gammaretroviral infection and raises the possibility of using the macrophage tropism of F-MLV in gene therapy.
Insights
Gammaretroviruses typically cannot infect nondividing cells. However, human macrophages become susceptible to Friend murine leukemia virus (F-MLV) vector transduction during differentiation, opening new gene therapy possibilities.
Area of Science:
- Virology
- Cell Biology
- Gene Therapy
Background:
- Gammaretroviruses, like murine leukemia viruses, are generally inefficient at infecting nondividing cells.
- This inefficiency is often attributed to the inability of these viruses to cross the nuclear envelope barrier.
Purpose of the Study:
- To challenge the notion that nondividing cells are completely resistant to gammaretroviral infection.
- To investigate the susceptibility of human macrophages to gammaretroviral vectors during differentiation.
Main Methods:
- Utilized a Friend murine leukemia virus (F-MLV)-derived vector for transduction experiments.
- Focused on human monocyte-derived macrophages during their differentiation process.
Main Results:
- Demonstrated a specific window of susceptibility to F-MLV vector transduction in human nondividing macrophages.
- Identified that macrophage differentiation influences permissiveness to gammaretroviral infection.
Conclusions:
- Nuclear membrane crossing is not the sole determinant of gammaretroviral infection permissiveness in nondividing cells.
- The macrophage tropism of F-MLV vectors presents potential applications in gene therapy.

