Innate sensing of foamy viruses by human hematopoietic cells

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Foamy viruses (FV) are nonpathogenic retroviruses with a long history of primate cospeciation.
• Human infection with FV typically results from primate bites, with low viral loads and no secondary transmission.
• The innate immune response of human hematopoietic cells to FV remains poorly understood, with prior studies suggesting a lack of type I interferon induction.

Purpose of the Study:

• To investigate the capacity of human hematopoietic cells to sense foamy viruses (FV) and FV-infected cells.
• To determine if FV can trigger an innate immune response, specifically type I interferon (IFN) production.

Main Methods:

• Peripheral blood mononuclear cells (PBMCs), plasmacytoid dendritic cells (pDCs), and the pDC-like cell line Gen2.2 were used to assess FV recognition.
• Type I IFN and IFN-stimulated gene MxA expression were measured.
• Inhibitors of endosomal acidification and Toll-like receptor (TLR) antagonists were employed.
• RNA silencing was used to identify specific TLR involvement.

Main Results:

• Human PBMCs, pDCs, and Gen2.2 cells detect FV and produce high levels of type I IFN and MxA.
• As few as 20 FV-infected cells can elicit an IFN response.
• IFN production is dependent on endosomal acidification and involves TLR7.
• A replication-defective FV induced IFN production, while a non-particle-producing FV strain did not.

Conclusions:

• Foamy viruses (FV) are potent inducers of type I interferon (IFN) in human pDCs and PBMCs.
• The innate immune response, particularly via TLR7, plays a significant role in sensing FV.
• This immune activation may be crucial for controlling FV replication in humans.