All Phenotypes Dpp4<em1Rba> MGI Mouse

increased neutrophil cell number ( J:279723 )

• MERS-CoV maM35C4-infected mice show elevated numbers and frequencies of neutrophils by 2 dpi and remain elevated but slowly wane

decreased lymphocyte cell number ( J:279723 )

• MERS-CoV maM35C4-infected mice show reduced numbers of lymphocytes on 2-4 dpi

increased monocyte cell number ( J:279723 )

• MERS-CoV maM35C4-infected mice show elevated numbers and frequencies of monocytes by 2 dpi

lung inflammation ( J:279834 )

• inflammatory infiltrates are seen in the lungs of mice infected with MERS-15 intranasally at day 3 post infection

increased susceptibility to Coronaviridae infection ( J:279723 , J:279834 )

• mice infected with a mouse adapted MERS-CoV strain maM35C4 lose weight over time, and show rapid and high viral titers in lung tissue peaking 2 days post-infection (dpi) and reducing slightly by 4 dpi (J:279723)

• neutrophil numbers on 1 dpi in peripheral blood of mice infected with a lethal dose of MERS-CoV is predictive of disease severity (J:279723)

• mice support efficient infection and replication of the human Middle East respiratory syndrome coronavirus (MERS-CoV) strain HCoV-EMC/2012 , camel strain Dromedary/Al-Hasa-KFU-HKU13/2013 , and recombinant virus derived from a molecular infectious clone (icMERS) in the lungs which is not seen in wild-type controls (J:279834)

• a MERS-CoV tissue-culture adapted variant with a 3 amino acid insertion (RMR) and single amino acid change in the S2 region (S885L), MERS-0, shows enhanced replication in the lungs of mice, with mice showing nucleocapsid antigen from MERS-0 in the lungs and lungs showing moderate respiratory pathology and inflammation but no severe clinical disease symptoms (J:279834)

• mice infected with MERS-15, a mouse adapted MERS-CoV (MERS-0) via serial passage for 15 rounds through the lungs of heterozygous Dpp4^em1Rba mice, intranasally show higher levels of MERS-15 replication in the lungs at 3 and 6 days post infection, while MERS-0 is cleared from the lungs by 6 days post infection and no replication is seen in wild-type mice (J:279834)

• however, no viral transcripts are seen in the brains of MERS-15 infected mice (J:279834)

• infection with one of two viral clones, MERS-15 C1 (containing mutations in nsP2 and a deletion from orf4b into orf5) or MERS-15 C2 (containing mutations in nsP2, nsP6, and nsP8, and a large deletion in orf4b), results in increased mortality, increased hemorrhage, 25-30% weight loss, high levels of virus replication, and lung pathology, with higher mortality and hemorrhage seen with MERS-15 C2 infection than MERS-15 C1 infection (J:279834)

• treatment of mice with human 3B11 antibody targeting the receptor-binding domain of the MERS-CoV spike protein provides 100% protection against MERS-15 C2 challenge (J:279834)

• mice vaccinated with Venezuelan equine encephalitis replicon particles expressing MERS-CoV spike protein show protection from developing severe respiratory disease and lethal MERS-15 C2 infection challenge (J:279834)

increased susceptibility to Coronaviridae infection induced morbidity/mortality ( J:279834 )

• intranasal infection of mice with the MERS-15, a mouse adapted MERS-CoV (MERS-0) via serial passage for 15 rounds through the lungs of heterozygous Dpp4^em1Rba mice, results in approximate 70% mortality

• infection with one of two viral clones, MERS-15 C1 (containing mutations in nsP2 and a deletion from orf4b into orf5) or MERS-15 C2 (containing mutations in nsP2, nsP6, and nsP8, and a large deletion in orf4b), results in increased mortality, with higher mortality with MERS-15 C2 infection than MERS-15 C1 infection

increased susceptibility to Coronaviridae infection induced morbidity/mortality ( J:279834 )

• intranasal infection of mice with the MERS-15, a mouse adapted MERS-CoV (MERS-0) via serial passage for 15 rounds through the lungs of heterozygous Dpp4^em1Rba mice, results in approximate 70% mortality

• infection with one of two viral clones, MERS-15 C1 (containing mutations in nsP2 and a deletion from orf4b into orf5) or MERS-15 C2 (containing mutations in nsP2, nsP6, and nsP8, and a large deletion in orf4b), results in increased mortality, with higher mortality with MERS-15 C2 infection than MERS-15 C1 infection

lung hemorrhage ( J:279834 )

• severe hemorrhage in the lungs is seen in mice infected with MERS-15 intranasally at days 3 and 6 post infection

pulmonary alveolar edema ( J:279834 )

• mice infected with MERS-15 intranasally show intra-alveolar edema

lung inflammation ( J:279834 )

• inflammatory infiltrates are seen in the lungs of mice infected with MERS-15 intranasally at day 3 post infection

increased susceptibility to pulmonary hyaline membrane formation ( J:279834 )

• mice infected with MERS-15 intranasally show hyaline membrane formation at day 6 post infection

respiratory distress ( J:279834 )

• mice infected with MERS-15 intranasally show increased enhanced pause (Penh), a measure reflecting airway obstruction/restriction due to debris in the airway, and increased midtidal expiratory flow (EF50), representing the flow rate at which 50% of tidal volume is expelled in a single breath, up to day 6 post infection indicating severe respiratory distress

• mice infected with MERS-15 intranasally show pathology associated with severe acute respiratory distress, including hyaline membrane formation, intra-alveolar edema, perivascular cuffing and severe inflammation at day 6 post infection