Author: Agnihothram, Sudhakar; Yount, Boyd L.; Donaldson, Eric F.; Huynh, Jeremy; Menachery, Vineet D.; Gralinski, Lisa E.; Graham, Rachel L.; Becker, Michelle M.; Tomar, Sakshi; Scobey, Trevor D.; Osswald, Heather L.; Whitmore, Alan; Gopal, Robin; Ghosh, Arun K.; Mesecar, Andrew; Zambon, Maria; Heise, Mark; Denison, Mark R.; Baric, Ralph S.
Title: A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant Document date: 2014_3_25
ID: y4zoyqua_23
Snippet: BtCoV HKU5-SE replicated efficiently in multiple cell types and used mouse ACE2 for entry into mice. The virus replication efficiency was reduced in interferon-competent Calu3 cells but not in Vero cells, similar to the results for SARS-CoV, suggesting the possibility of limited control by cell-intrinsic immune mechanisms as reported with SARS-CoV (38) . Of interest, the ORF4b genes of group 2c strains like HKU5 and MERS-CoV are closely related a.....
Document: BtCoV HKU5-SE replicated efficiently in multiple cell types and used mouse ACE2 for entry into mice. The virus replication efficiency was reduced in interferon-competent Calu3 cells but not in Vero cells, similar to the results for SARS-CoV, suggesting the possibility of limited control by cell-intrinsic immune mechanisms as reported with SARS-CoV (38) . Of interest, the ORF4b genes of group 2c strains like HKU5 and MERS-CoV are closely related and encode interferon antagonist activities, as detected using reporter assays (39) . Using reverse genetics, our group and others have deleted these interferon antagonists from MERS-CoV (40, 41) , with little to no effect on virus growth in vitro. The BtCoV HKU5-SE molecular clone would enable the dissection of related interferon antagonist activities in accessory ORFs of other group 2c CoVs, identifying common and unique pathways for regulating innate immune responses in human cells. It is noteworthy that ORF5 is not essential for the replication of either MERS-CoV or BtCoV HKU5-SE.
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