Title : Rapid generation of a mouse model for Middle East respiratory syndrome - Zhao_2014_Proc.Natl.Acad.Sci.U.S.A_111_4970 |
Author(s) : Zhao J , Li K , Wohlford-Lenane C , Agnihothram SS , Fett C , Gale MJ, Jr. , Baric RS , Enjuanes L , Gallagher T , McCray PB, Jr. , Perlman S |
Ref : Proc Natl Acad Sci U S A , 111 :4970 , 2014 |
Abstract :
In this era of continued emergence of zoonotic virus infections, the rapid development of rodent models represents a critical barrier to public health preparedness, including the testing of antivirus therapy and vaccines. The Middle East respiratory syndrome coronavirus (MERS-CoV) was recently identified as the causative agent of a severe pneumonia. Given the ability of coronavirus to rapidly adapt to new hosts, a major public health concern is that MERS-CoV will further adapt to replication in humans, triggering a pandemic. No small-animal model for this infection is currently available, but studies suggest that virus entry factors can confer virus susceptibility. Here, we show that mice were sensitized to MERS-CoV infection by prior transduction with adenoviral vectors expressing the human host-cell receptor dipeptidyl peptidase 4. Mice developed a pneumonia characterized by extensive inflammatory-cell infiltration with virus clearance occurring 6-8 d after infection. Clinical disease and histopathological changes were more severe in the absence of type-I IFN signaling whereas the T-cell response was required for virus clearance. Using these mice, we demonstrated the efficacy of a therapeutic intervention (poly I:C) and a potential vaccine [Venezuelan equine encephalitis replicon particles expressing MERS-CoV spike protein]. We also found little protective cross-reactivity between MERS-CoV and the severe acute respiratory syndrome-CoV. Our results demonstrate that this system will be useful for MERS-CoV studies and for the rapid development of relevant animal models for emerging respiratory viral infections. |
PubMedSearch : Zhao_2014_Proc.Natl.Acad.Sci.U.S.A_111_4970 |
PubMedID: 24599590 |
Zhao J, Li K, Wohlford-Lenane C, Agnihothram SS, Fett C, Gale MJ, Jr., Baric RS, Enjuanes L, Gallagher T, McCray PB, Jr., Perlman S (2014)
Rapid generation of a mouse model for Middle East respiratory syndrome
Proc Natl Acad Sci U S A
111 :4970
Zhao J, Li K, Wohlford-Lenane C, Agnihothram SS, Fett C, Gale MJ, Jr., Baric RS, Enjuanes L, Gallagher T, McCray PB, Jr., Perlman S (2014)
Proc Natl Acad Sci U S A
111 :4970