INFLUENCE OF TYPE 2 BOVINE VIRAL DIARRHEA VIRUS NPRO ON ENHANCEMENT OF BOVINE RESPIRATORY SYNCYTIAL VIRUS REPLICATION MEDIATED BY ANTAGONISM OF HOST CELL INTERFERON TYPE I RESPONSES

Bovine viral diarrhea virus (BVDV) is a member of the genus Pestivirus, Family Flaviviridae. The virus can infect many species of animals of the order Artiodactyla. The BVDV genome encodes an auto protease, Npro, that degrades interferon regulatory factor-3 (IRF-3) reducing type I interferon (IFN-I) production from host cells. Bovine respiratory syncytial virus (BRSV) is a member of the genus Pneumovirus, Family Paramyxoviridae. Concurrent infection with BVDV and BRSV causes more severe respiratory and enteric disease than infection with either virus alone. Our hypothesis was that Npro modulates the innate immune responses to BVDV infection and enhances replication of BVDV or BRSV co-infection. The noncytopathic BVDV2 viruses NY93/c N- Npro 18 EGFP (a mutant with modified Npro fused with enhanced green fluorescent protein), NY93 infectious clone (NY93/c), wild-type NY93-BVDV2 (NY93-wt), and BRSV were evaluated in this study. The objectives of this study were: (1) to characterize the replication kinetics and IFN-I induction in Madin-Darby bovine kidney (MDBK) cells following infection with each of the BVDV isolates, and (2) to characterize the influence of BVDV-mediated IFN-I antagonism on enhancement of BRSV replication in bovine turbinate (BT) cells. NY93/c N- Npro 18 EGFP replicated 0.4 – 1.6 TCID50 logs lower than NY93-wt in MDBK cells. NY93/c N- Npro 18 EGFP-infected MDBK cells synthesized IFN-I significantly higher than NY93/c- and NY93-wt-infected MDBK cells. BT cells co-infected with NY93/c N- Npro 18 EGFP/BRSV or NY93-wt/BRSV were evaluated to determine the effects of co-infection on BRSV replication and IFN-I induction in BT cells. BRSV RNA levels in NY93-wt/BRSV co-infected BT cells were 2.49, 2.79, and 2.89 copy number logs significantly greater than in NY93/c N- Npro 18 EGFP/BRSV co-infected BT cells on days 5, 7, and 9 post-infection, respectively. BVDV RNA levels in NY93/c N- Npro 18 EGFP-infected BT cells were 1.64 – 4.38 copy number logs lower than in NY93-wt-infected BT cells. NY93/c N- Npro 18 EGFP single and co-infected BT cells synthesized IFN-I significantly higher than NY93-wt single and co-infected BT cells. In summary, these findings suggest: (1) NY93/c N- Npro 18 EGFP BVDV2 induced higher levels of IFN-I than BVDV2-wt and may be useful as a safer, replicating BVDV vaccine, and (2) Enhancement of BRSV infection by BVDV co-infection is mediated by antagonism of IFN-I.

The People's Hour and the Social Gospel: George Howard Gibson's Gilded Age Search for an Organization of the Kingdom of God

Previous studies of the Social Gospel movement have acknowledged the fact that Social Gospelers were involved in multiple social reform movements during the Gilded Age and into the Progressive Era. However, most of these studies have failed to explain how the reform experiences of the Social Gospelers contributed to the development of the Social Gospel. The Social Gospelers’ ideas regarding the need to transform society and their strategies for doing so were largely a result of their personal experiences as reformers and their collaboration with other reformers. The knowledge and insight gained from interaction with a variety of reform methods played a vital role in the development of the ideology and theology of the Social Gospel. George Howard Gibson is exemplary of the connections between the Social Gospel movement and several other social reform movements of the time. He was involved in the Temperance movement, was a member of both the Prohibition Party and the People’s Party, and co-founded a Christian socialist cooperative colony. His writings illustrate the formation of his identity as a Social Gospeler as well as his attempts to find an organization through which to realize the kingdom of God on earth. Failure to achieve the changes he desired via prohibition encouraged him to broaden his reform goals. Like many Midwestern Social Gospelers Gibson believed he had found “God’s Party” in the People’s Party, but he rejected reform via the political system once the Populists restricted their attention to the silver issue and fused with the Democratic Party. Yet his involvement with the People’s Party demonstrates the attraction many Social Gospelers had to the reforms proposed in the Omaha Platform of 1892 as well as to the party’s use of revivalistic language and emphasis on producerism and brotherhood. Gibson’s experimentation with a variety of ways to achieve the kingdom of God on earth provides new insight into the experiences and contributions of lay Social Gospelers. Adviser: Kenneth J. Winkle