The virological synapse facilitates herpes simplex virus entry into T cells

Area of Science:

• Virology and Immunology
• Cellular Biology
• Infectious Diseases

Background:

• The virological synapse (VS) facilitates lymphotropic virus transfer to T cells.
• The role of VS in nonlymphotropic virus transfer, like Herpes simplex virus (HSV), into T cells remains unclear.
• HSV infection of T cells in vitro can suppress T-cell function, but in vivo occurrence is unknown.

Purpose of the Study:

• To investigate HSV-infected T cells in human disease.
• To elucidate the mechanism of HSV entry into T cells.
• To determine if HSV utilizes the virological synapse for T cell infection.

Main Methods:

• Detection of HSV-infected T cells in human disease samples.
• Analysis of HSV cell-to-cell spread efficiency versus cell-free infection.
• Investigation of HSV entry receptors (gD, nectin-1, herpesvirus entry mediator) and T-cell activation effects.
• Microscopic observation of VS-like structures and assessment of LFA-1 involvement.

Main Results:

• HSV-infected T cells (CD4+ and CD8+) were detected in human disease.
• Cell-to-cell spread from fibroblasts to T cells was more efficient than cell-free infection.
• T-cell activation increased HSV permissivity; spread required gD but not gE/gI.
• VS-like structures involving LFA-1 were observed, and LFA-1 activation enhanced spread, while antibodies blocked it.

Conclusions:

• This study demonstrates VS-dependent cell-to-cell spread of HSV to T cells.
• HSV infection and immunomodulation of T cells play a role in human immunopathology.
• Targeting the virological synapse may offer a strategy for immunopotentiation in HSV infections.