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Apoptosis and HSV-2 infection

European researchers studied the role of apoptosis following herpes simplex virus type 2 (HSV-2) infection. By focusing on the inflammatory response at the initial stage of infection and further recruitment of immune-competent cells, they wished to provide insight into the events following HSV-2 infection.
Apoptosis and HSV-2 infection
The prevalence of HSV-2 infections is quite high, ranging from 10–60 %. The latent nature of the virus means that recurrent infections may occur, thereby influencing the integrity and functioning of vaginal mucosa and increasing the risk of HIV transmission.

One of the ways our immune system tackles infections is by inducing apoptosis of infected cells, using cell-surface death receptors such as the Fas (Apo-1, CD95) protein and its ligand, FasL (CD178). Accumulating evidence indicates that Fas mediates other processes beyond apoptosis, including proliferation, angiogenesis, fibrosis and inflammation.

Against this backdrop, the EU-funded project 'The role of Fas/FasL in maintenance of vaginal epithelium integrity during HSV-2 infection' (FASVAG/HSV-2) was established to investigate further. The project researchers took an experimental approach, infecting mice that lack the Fas receptor and FasL with HSV-2.

Close examination of the vaginal epithelium of infected animals showed lower release of pro-inflammatory cytokines and chemokines by host monocytes, as well as reduced infiltration by immune cells. This clearly suggested that the Fas/FasL axis is implicated in local cytokine and chemokine secretions after HSV-2 infection, which further influences migration and turn-over of immune cells.

Additionally, compared to wild-type mice, Fas/FasL knockout mice presented inefficient mobilisation of natural killer (NK) cells and CD8+ cells concomitant with high virus titres and a delayed virus clearance from the vaginal tissue. These findings underscore the importance of the Fas/FasL pathway in mounting efficient immune responses against HSV-2.

Apart from providing insight into the mechanism of HSV-2 infection, the results of the FASVAG/HSV-2 study have clinical significance too. The modulation of Fas/FasL expression could be exploited for the development of effective vaginal microbicides against HSV-2.

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