Secreted NS1 proteins of tick-borne encephalitis virus and West Nile virus block dendritic cell activation and effector functions

Flavivirus non-structural protein 1 (NS1) is secreted from cells in infected individuals and in cell culture and levels correlate with disease severity. Treatment of murine bone marrow–derived dendritic cells (BMDCs) with recombinantly produced solube NS1 (sNS1) of tick-borne encephalitis virus (TBEV) or West Nile virus (WNV) prior to poly(I:C) stimulation revealed two gene clusters that were downregulated by TBEV or WNV sNS1 and that were associated with innate and adaptive immune responses. Especially co-stimulatory molecules and pro-inflammatory cytokines as well as chemokines were found to be downregulated in sNS1 pre-treated BMDCs prior to poly(I:C) stimulation. Overall design: BMDCs were left untreated, or stimulated with poly(I:C), or pre-treated with TBEV or WNV sNS1 for 16 h and stimulated with poly(I:C) for 24 h. RNA from 3 replicates in each condition was extracted using Trizol and the Directzol Miniprep Plus Kit, and sequenced on Illumina NovaSeq platform with 100 bp paired-end read configuration.