LncRNA NRAV promotes respiratory syncytial virus (RSV) replication by regulating vesicle transportation via targeting miR-509-3p/Rab5c axis

Respiratory syncytial virus (RSV) is an enveloped RNA virus which is responsible for approximately 80% of lower respiratory tract infections in children. Current lines of evidence have supported the functional involvement of long non-coding RNA (lncRNA) in many viral infectious diseases. However, the overall biological effect and clinical role of lncRNAs in RSV infection remain unclear. In this study, lncRNAs related to respiratory virus infection were obtained from lncRNA database. And we collected 144 clinical sputum specimens to identify lncRNAs related to RSV infection. qPCR detection indicated that the expression of lncRNA NRAV in RSV-positive patients was significantly lower than that in uninfected ones, but lncRNA PRINS, NEAT1, and NEST showed no difference in vivo and in vitro Meanwhile, over expression of Negative Regulator of Antiviral Response (NRAV) promoted RSV proliferation in A549 and BEAS-2B cells, and vice versa, indicating that the down-regulation of NRAV was part of the host antiviral defense. RNA FISH confirmed that NRAV was mainly located in the cytoplasm. Through RNA sequencing we found that Rab5c, which is a vesicle transporting protein, showed the same change trend as NRAV. Subsequent investigation revealed that NRAV was able to favor RSV production indirectly by sponging miR-509-3p so as to release Rab5c and facilitate vesicle transportation. The study provides a new insight into virus-host interaction through non-coding RNA, which may contribute to exploring potential antivirus target for respiratory virus.IMPORTANCE Mechanism of interaction between RSV and host non-coding RNAs has not been fully understood. In this study, we found that the expression of lncRNA NRAV was reduced in RSV-infected patients, and over-expression of NRAV facilitated RSV production in vitro, suggesting that the reduction of NRAV in RSV infection was part of the host antiviral response. We also found that NRAV competed with vesicle protein Rab5c for miR509-3p in cytoplasm, to promote RSV vesicle transport and accelerate RSV proliferation, thereby improving our understanding of the pathogenic mechanism of RSV infection.