Hindering Herpes

Science Signaling  14 Oct 2008:
Vol. 1, Issue 41, pp. ec357
DOI: 10.1126/scisignal.141ec357

Reactivation of herpes simplex virus (HSV) from neuronal latency is a common and potentially devastating cause of disease worldwide. Now Knickelbein et al. demonstrate the use of the lytic granule components perforin and granzyme B by HSV-specific CD8+ T cells in maintaining HSV-1 latency in sensory neurons both in vivo and in vitro. Lytic granules polarized to T cell/neuron junctions during immunosurveillance of latently infected neurons, which are selectively resistant to apoptosis induction by HSV-specific CD8+ T cells. The lytic granule component, granzyme B, inhibited viral gene expression through cleavage of a viral immediate early protein required for expression of early and late genes. Thus, lytic granules can function in a noncytotoxic manner, and granzyme B targets a viral protein that is required for further viral gene expression.

J. E. Knickelbein, K. M. Khanna, M. B. Yee, C. J. Baty, P. R. Kinchington, R. L. Hendricks, Noncytotoxic lytic granule-mediated CD8+ T cell inhibition of HSV-1 reactivation from neuronal latency. Science 322, 268-271 (2008). [Abstract] [Full Text]