Autocrine Interferon Priming in Macrophages but Not Dendritic Cells Results in Enhanced Cytokine and Chemokine Production after Coronavirus Infection

Zhou, Haixia; Zhao, Jincun; Perlman, Stanley

To determine whether cytokine production by BMM required virus replication, we exposed BMM to UV-inactivated MHV prior to treatment with IFN-␤. IFN-␤ treatment did not stimulate expression (Fig. 6B) . Treatment with IFN-␤ enhanced IFN production in MHV-infected BMM at 8 h p.i. (Fig. 6B) , which suggests that the levels of MHV-induced IFN were insufficient to maximally increase IFN-␣/␤ expression at this time p.i. However, by 16 h p.i., MHV induced sufficient amounts of IFN so that exogenous IFN had no additional effects (Fig. 6B) . No IFN protein was detected in either MHV-infected BMDC or 17Cl-1 cells (32, 43) , but low levels of IFN mRNA were detected at late times p.i. in these cells (23) . Treatment of MHV-infected BMDC with IFN induced significantly (P Ͻ 0.01) higher levels of IFN-␣/␤ mRNA than did IFN-␤ treatment or MHV infection alone, when measured at 16 h p.i., although the levels were only about 2% of those observed in infected BMM. In 17Cl-1 cells, IFN-␣/␤ was expressed at very low levels after infection, even after IFN-␤ treatment (Fig. 6B) . Combined with data generated from IFNAR Ϫ/Ϫ BMM, these results suggest that virus replication is required to initiate production of type I IFN, which functions by autocrine signaling to reach maximal levels.