09 July 2020
Restoring cellular resistance to herpes virus
Published online 4 January 2013
Children infected with herpes simplex virus-1 (HSV-1) are prone to encephalitis, an acute inflammation of the brain. It is unknown how the virus migrates from the mouth and nose to the brain, outsmarting the central nervous system's (CNS) immune system along the way.
An international team of researchers, including Saleh Al-Muhsen from King Saud University, Riyadh, has found that the nerve cells of HSV-1-infected children lack a functional toll-like receptor 3 (TLR3), a protein located at the cell-surface, and UNC-93B, an intracellular protein.
Both TLR3 and UNC-93B help generate interferons (IFN), a type of protein that fights viral infection. To investigate the role of interferons in resisting HSV-1, the team prepared induced pluripotent stem cells (iPS) using dermal fibroblast cells from HSV-1 uninfected children, and TLR3-deficient and UNC-93b-deficient cells from HSV-1-infected children.
The researchers found that treating the UNC-93B-deficient and TLR3-deficient neurons with interferons (alpha- or beta-interferon), or expressing UNC-93B and TLR3 in neurons restored their resistance to HSV-1 infection.
"These results suggest that interferon treatment, in addition to acyclovir, an anti-viral drug, may benefit the therapeutic outcome of HSV-1-triggered encephalitis in children," says Shen-Ying Zhang, co-author of the paper.
- Lafaille, F. G. et al. Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells. Nature 491, 769-773 (2012) doi:10.1038/nature11583