Avian paramyxovirus serotype 2 ( @entity26494 -2) is one of the nine serotypes of @entity26494 , which infect a wide variety of avian species around the world. In this study, we constructed a reverse genetics system for recovery of infectious recombinant @entity26494 -2 strain Yucaipa ( @entity26494 -2/Yuc) from cloned cDNA. The rescued recombinant virus (rAPMV-2) resembled the biological virus in growth properties in vitro and in pathogenicity in vivo. The reverse genetics system was used to analyze the role of the cleavage site of the fusion (F) protein in viral replication and pathogenesis. The cleavage site of @entity26494 -2/Yuc (KPASR   F) contains only a single basic residue (position -1) that matches the preferred furin cleavage site [RX(K/R)R   ]. (Underlining indicates the basic @entity1522 at the F protein cleavage site, and the arrow indicates the site of cleavage.) Contrary to what would be expected for this cleavage sequence, @entity26494 -2 does not require, and is not augmented by, exogenous protease supplementation for growth in cell culture. However, it does not form syncytia, and the virus is avirulent in @entity1573 . A total of 12 @entity26494 -2 mutants with F protein cleavage site sequences derived from @entity26494 serotypes 1 to 9 were generated. These sites contain from 1 to 5 basic residues. Whereas a number of these cleavage sites are associated with protease @entity734 and lack of syncytium formation in their respective native viruses, when transferred into the @entity26494 -2 backbone, all of them conferred protease independence, syncytium formation, and increased replication in cell culture. Examination of selected mutants during a pulse-chase experiment demonstrated an increase in F protein cleavage compared to that for wild-type @entity26494 -2. Despite the gains in cleavability, replication, and syncytium formation, analysis of viral pathogenicity in 9-day-old embryonated @entity1573 eggs, 1-day-old chicks, and 2-week-old @entity1573 showed that the F protein cleavage site mutants did not exhibit increased pathogenicity and remained avirulent. These results imply that structural features in addition to the cleavage site play a major role in the cleavability of the F protein and the activity of the cleaved protein. Furthermore, cleavage of the F protein is not a determinant of @entity26494 -2 pathogenicity in @entity1573 .

Mutations in the fusion protein cleavage site of avian paramyxovirus serotype 2 increase cleavability and syncytium formation but do not increase viral virulence in XXXX .

@entity1573 :: ('9031', 'Species') :: ['chickens', 'chicken'] @entity1522 :: ('CHEBI:33709', 'Chemical') :: ['amino acids'] @entity734 :: ('MESH:D019966', 'Disease') :: ['dependence'] @entity26494 :: ('12319', 'Species') :: ['APMV']
@entity1573 :: (9031,Species) :: ['chickens']
