Postentry restriction to human immunodeficiency virus-based vector transduction in human monocytes.

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• Monocytes are key cells in the immune system and can be infected by HIV-1.
• Efficient gene delivery to antigen-presenting cells is crucial for immunotherapy and vaccine development.

Purpose of the Study:

• To investigate the efficiency of HIV-1-based vectors in transducing human monocytes, macrophages, and dendritic cells (DCs).
• To develop an effective protocol for antigen gene delivery to human antigen-presenting cells using HIV-1 vectors.

Main Methods:

• Examined transduction of freshly isolated monocytes, in vitro differentiated macrophages, and dendritic cells (DCs) using HIV-1-based vectors.
• Analyzed the role of HIV-1 accessory proteins and vector components in transduction efficiency.
• Assessed reverse transcription and nuclear entry of the vector in different cell types.

Main Results:

• Freshly isolated monocytes were resistant to HIV-1 vector transduction, while mature macrophages showed increased susceptibility.
• A block in vector nuclear entry was identified in monocytes, preventing the formation of 2LTR circles.
• Subsequent differentiation of monocytes into DCs rescued transduction, facilitated by fetal calf serum promoting vector nuclear entry.

Conclusions:

• HIV-1 vector transduction of monocytes is maturation-dependent and blocked at nuclear entry.
• Differentiation into dendritic cells overcomes the nuclear entry block, enabling gene delivery.
• This study provides insights for developing gene delivery strategies to antigen-presenting cells using HIV-1 vectors.