Viral infection induces an innate immune response in neurons, a group led by Monique Lafon at the Pasteur Institute in Paris, France, has found. It was previously thought that the nervous system relied solely on glial cells to detect infection.

Lafon and colleagues used in vitro cultures of a human postmitotic neuron-derived cell line, NT2-N, which displays characteristics of fully mature human neurons upon transplantation into the brain, and infected them with rabies virus (RABV) or herpes simplex type 1 virus (HSV-1).

Searching for neuronal genes of which transcription is upregulated during infection through microarray analysis (using cut-off of a twofold increase to identify upregulated genes), they found that RABV infection increased the transcription of 228 genes, and HSV-1 infection increased the transcription of 263 genes. RABV upregulated 56 genes of the immunity cluster of genes (24% of all genes upregulated by RABV), whereas HSV-1 upregulated only 13 genes in this cluster (4.9% of all genes upregulated by HSV-1). Of all the genes upregulated by RABV, the 25 genes for which expression was most strongly stimulated were all involved in the innate immune response, including the interferon-β (IFN-β) gene, IFN-β primary and secondary response genes, as well as genes for chemokines, inflammatory cytokines and molecules with antiviral activities. Infection with HSV-1, on the other hand, did not upregulate IFN-β gene transcripts. Microarray results were confirmed by real-time PCR, immunocytochemistry and ELISA.

Microarray analysis also revealed that NT2-N cells express genes that code for molecules which can sense double-stranded RNA (dsRNA, a molecular signature of RNA viruses), including Toll-like receptor 3 (TLR3). This was confirmed by immunocytochemistry using antibody directed against the human TLR3. Treatment of NT2-N cells with dsRNA led to the upregulation of some genes that are involved in innate immunity. Similar treatment with lipopolysaccharide, found on the outer leaflet of the outer membrane of Gram-negative bacteria, had limited effect. In addition, human postmitotic neurons were responsive to a treatment with IFN-β, suggesting that they also express receptors to IFN-α/β (IFN-Rα/β).

These results establish that human neurons are capable of sensing and responding to viral infection, and that dsRNA could be the main viral element that is sensed by human neurons as a trigger of an innate immune response.