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

Exogenous IFN enhances expression of cytokines and other IFN-dependent molecules in MHV-infected BMM at early but not late times p.i. Our results suggested that BMM expression of several inflammation-related molecules, including IFN-␣/␤, MDA5, RIG-I, and CXCL10, required signaling through the IFNAR. However, from these results, it could not be determined whether upregulated expression of these molecules occurred solely as a consequence of MHV-induced IFN induction or if some aspect of virus replication synergistically enhanced expression. Further, the amount of IFN produced in MHV-infected BMM was much lower than in SenV-infected cells, raising questions as to whether this amount was sufficient to fully upregulate these IFN-induced genes. To address these questions, we treated mock-infected or MHV-infected BMM with IFN-␤ and then measured mRNA levels of inflammatory molecules by real-time qPCR. The cells were treated with IFN-␤ at 4 h p.i. to minimize any effect that IFN treatment might have on virus replication; we could not detect any MHV-induced IFN-␤ RNA or IFN protein at this time p.i. (Fig. 1C) . We used a high dose of IFN (800 U of murine IFN-␤) so that any IFN-mediated effects would be readily apparent. For comparison, we also treated mock-and MHVinfected BMDC and 17Cl-1 cells with IFN, since IFN was barely detected at any time p.i. in these cells. IFN treatment did not reduce virus titers in any of these cells, when measured at 16 h p.i. (Fig. 6A) , consistent with previous reports (13, 32, 33) .