Scientists know that early immune responses to viral infection can inhibit virus replication. But a new study from National Institutes of Health (NIH) scientists suggests that, in the brain, the same process can lead to the destruction of neurons, the information-processing cells of the central nervous system. The results are described online in the March 14, 2013, issue of Immunity.
By studying LACV infection in cell cultures of neurons and in mice, scientists from NIAID determined that LACV uses a protein called MAVS to activate early immune responses. They then showed how MAVS induces another immune system protein, SARM1, to kill neurons (SARM1 binds to and damages mitochondria—the cells’ energy source). In study models where scientists removed SARM1, significantly fewer neurons died despite similar LACV infection.
Normally, MAVS stimulates the immune system to produce type 1 interferon, which limits infecting virus from replicating and spreading. In neurons, however, MAVS activation results in the death of the neuron by inducing the production of SARM1.
Activation of early immune responses is common in a number of neurological diseases, ranging from Alzheimer’s disease to viral encephalitis. By showing that these early immune responses can induce neuronal death in the brain, this study suggests that activating SARM1 could do the same in other neurological diseases.
The NIAID scientists plan to determine if SARM1 causes neuronal death in other neurological disease. The group also is exploring why neurons in the brain are sensitive to this pathway of cell death whereas other types of cells in the brain are not.
et al. Activation of the innate signaling molecule MAVS by Bunyavirus infection upregulates the adaptor protein SARM leading to neuronal death. Immunity DOI: 10.1016/j.immuni.2013.02.013 (2013).
Last Updated March 13, 2013
Last Reviewed March 13, 2013