Human Respiratory syncytial virus (hRSV) is the most common pathogen which causes acute lower respiratory infection (ALRI) in infants. Recently, virus-host interaction is a hot spot of virus related research, and it needs to be further elaborated on its host interactions during RSV infection. Here, we found that RSV infection significantly increased the expression of cypA in clinical patients, mice or epithelial cells. Therefore, we evaluated the function of cypA in RSV replication and demonstrated that virus proliferation was accelerated in cypA knockdown host cells, but restrained in cypA overexpressed host cells. Furthermore, we proved that cypA limited RSV replication depending on its PPIase activity. Moreo... More
Human Respiratory syncytial virus (hRSV) is the most common pathogen which causes acute lower respiratory infection (ALRI) in infants. Recently, virus-host interaction is a hot spot of virus related research, and it needs to be further elaborated on its host interactions during RSV infection. Here, we found that RSV infection significantly increased the expression of cypA in clinical patients, mice or epithelial cells. Therefore, we evaluated the function of cypA in RSV replication and demonstrated that virus proliferation was accelerated in cypA knockdown host cells, but restrained in cypA overexpressed host cells. Furthermore, we proved that cypA limited RSV replication depending on its PPIase activity. Moreover, we performed liquid Chromatograph Mass Spectrometer and the results showed that cypA could interact with several viral proteins, such as RSV-N, RSV-P and RSV-M2-1. Finally, the interaction between cypA and RSV-N was certificated by co-immunoprecipitation and immunofluorescence. Those results provided strong evidence that cypA may play an inhibitory role in RSV replication through interacting with RSV-N via its PPIase activity.RSV-N, packed the viral genome to form the ribonuceloprotein complex (RNP), which is recognized by RSV RNA dependent RNA polymerase (RdRp) complex to initiate the viral replication and transcription, plays an indispensable role in viral biosynthesis process. CypA, binding to RSV-N, may impair this function by weakening the interaction between RSV-N and RSV-P, thus leading to decrease viral production. Our research provides a novel insight into cypA antiviral function by binding to viral capsid protein to inhibit viral replication, which may be helpful for new antiviral drug exploration.
