Recently, the waterfowl viral infectious diseases innovation team of Shanghai Veterinary Research Institute (SHVRI) published two research papers in Plos Pathogens. Studies have shown that Newcastle Disease Virus (NDV) infection inhibits the translation of host translation system. The interaction of its NP protein with host translation initiation factors promotes the preferential translation of viral mRNA. In addition, the rapid replication of NDV in cells activates double-stranded DNA breaks (DSBs) and promotes viral killing of tumor cells. This research expands the understanding of the interaction between NDV and host cells, and provides a new perspective for better prevention of Newcastle disease and construction of oncolytic viruses.
Newcastle disease virus (NDV), belonging to the Paramyxoviridae family, is a single-stranded negative-strand RNA virus. Newcastle disease caused by NDV is still one of the most harmful poultry diseases. In addition, NDV specifically replicates in human tumor cells and induces tumor cell death through exogenous and endogenous apoptosis pathways. The virus is a strict intracellular parasite that completely depends on the host's translation system to synthesize viral proteins. The host's eukaryotic translation system is an important regulatory target. The study first confirmed that the host translation system is suppressed post NDV infection. PI3k/Akt/mTOR and p38 MAPK/Mnk1 regulatory pathways are quickly activated by NDV infection. NP protein encoded by NDV directly binds to the host translation initiation factor eIF4E and preferentially translates NDV type 0 cap structure mRNA (Figure 1).
Figure 1 Newcastle disease virus hijacking host translation system
In addition, the rapid replication of viruses can also cause cell damage and trigger a series of cell biological events. The team found that NDV infection activate ATM-dependent double-stranded DNA breaks (DSBs). Co-transfection of viral HN and F protein induces cell fusion and activates DSBs through the MRN-ATM-H2A/53BP1-Chk2 pathway. The inhibition of ATM-dependent DSBs can significantly inhibit virus replication and membrane fusion in tumor cells (Figure 2).
Figure 2 Newcastle disease virus and HN-F-mediated cell fusion induces DNA damage
How NDV encoded structural proteins participates in the viral replication mechanism was not fully elucidated. The above results reveal the new functions of viral structural proteins NP, HN and F, and provide a theoretical basis for elucidating the replication mechanism of NDV and other paramyxoviruses.
Yuan Zhan and Shanhui Ren, the PhD students of SHVRI, Chinese Academy of Agricultural Sciences, were the first authors of the papers, respectively, and Chan Ding and Yingjie Sun were co-corresponding authors. The research was supported by the Key program of National Natural Science Foundation of China, National Key Research and Development Program of China and the Chinese Academy of Agricultural Sciences Science and Technology Innovation Project.
Paper link:
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008610
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008514
