Role of Small Hydrophobic Protein of J Paramyxovirus in Virulence

J paramyxovirus (JPV) was first isolated from moribund mice with hemorrhagic lung lesions in Australia in 1972. It is a paramyxovirus classified under the newly proposed genus Jellongvirus. JPV has a genome of 18,954 nucleotides, consisting of eight genes in the order 3'-N-PN/C-M-F-SH-TM-G-L-5'. JPV causes little cytopathic effect (CPE) in tissue culture cells but severe disease in mice. The small hydrophobic (SH) protein is an integral membrane protein encoded by many paramyxoviruses, such as mumps virus (MuV) and respiratory syncytial virus (RSV). However, the function of SH has not been defined in a suitable animal model. In this work, the functions of SH of JPV, MuV, and RSV have been examined by generating recombinant JPV lacking the SH protein (rJPV-Delta SH) or replacing SH of JPV with MuV SH (rJPV-MuV51-1) or RSV SH (rJPVRSVSH). rJPV-Delta SH, rJPV-MuVSH, and rJPV-RSVSH were viable and had no growth defect in tissue culture cells. However, more tumor necrosis factor alpha (TNF-alpha) was produced during rJPV-Delta SH infection, confirming the role of SH in inhibiting TNF-alpha production. rJPV-Delta SH induced more apoptosis in tissue culture cells than rJPV, rJPV-MuV51-1, and rJPV-RSVSH, suggesting that SH plays a role in blocking apoptosis. Furthermore, rJP-Delta ASH was attenuated in mice compared to rJPV, rJPV-MuVSH, and rJPV-RSVSH, indicating that the SH protein plays an essential role in virulence. The results indicate that the functions of MuV SH and RSV SH are similar to that of JPV SH even though they have no sequence homology. IMPORTANCE Paramyxoviruses are associated with many devastating diseases in animals and humans. J paramyxovirus (JPV) was isolated from moribund mice in Australia in 1972. Newly isolated viruses, such as Beilong virus (BeiPV) and Tailam virus (TImPV), have genome structures similar to that of JPV. A new paramyxovirus genus, Jeilongvirus, which contains JPV, BeiPV, and TImPV, has been proposed. Small hydrophobic (SH) protein is present in many paramyxoviruses. Our present study investigates the role of SH protein of JPV in pathogenesis in its natural host. Understanding the pathogenic mechanism of leilongvirus is important to control and prevent potential diseases that may emerge from this group of viruses.