Brain-resident memory cells (bT RM) and virus reactivation

Abstract Background Neuroimmune responses terminate MCMV acute infection, however, a subset of neurons still harbor latent viral genomes. Factors regulating reactivation remain to be elucidated. Methods Using RNAscope, IE1 nucleic acid was detected within brains at D5 and D30 p.i. real-time RT-PCR, we assessed expression IE1, E1, gB transcripts. multi-color flow cytometry, depletion bT RMfollowing icv injection either α-CD8 Ab or α-CD103-sap. luciferase-expressing transgenic mice, longitudinally cre-MCMV after T-cell using live small animal imaging. Explant assay employed study the role RMin reactivation. Nanostring, identified changes following RM-depletion. Results Brain infection demonstrated by X-gal staining as well RNAscope 5 d After 30 p.i., virus established latency, indicated absence transcripts (IE1, gB). establishment, injected α-CD103-sap into brain showed 90–95% depletion. We infected mice with cre-MCMV, which expresses Cre recombinase. observed enhanced imaging signals indicative IE promoter activity in depleted animals. Surprisingly, efficiently recovered from untreated but not those RM. Furthermore, on Nanostring analysis, gpnmband hmox1, upregulated 11.48- 6.7-fold RMdepletion. Conclusion When RM, there transient expression, sufficient activate surveying microglia. This eventually resulted tissue-wide anti-viral state. These data provide new insights controlling project supported award numbers NS-038836 National Institute Neurological Disorders Stroke