Recently, the Animal Influenza Basic and Prevention and Control Research Innovation Team of Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences modified Susuhua to affect influenza A virus (hereinafter referred to as influenza virus) to cause disease Significant progress has been made in research on the mechanism of transmission and transmission. For the first time, it was discovered that the Susuylation modification at the K612 site of the PB1 protein plays an important role in the pathogenicity and transmission of influenza viruses, and broadened the understanding of how the host’s post-translational modification system regulates the replication mechanism of influenza viruses. It also provides a reference for the research and development of anti-influenza virus drugs. Related research results will be published online in the journal”PloS Pathogens” on February 11, 2021.
According to researchers, the post-translational modification of influenza virus protein plays an important regulatory role in the replication process after the virus infects the host. At present, the NP of influenza virus is known , M1 and NS1 proteins can be modified by threonyl, but whether the PB1 protein, which is the core component of the viral polymerase complex, has been modified by threonyl and the effect of the modification on the virus replication cycle is still unknown.
This study found that the PB1 protein of different subtypes of influenza virus can be modified by threonin, and it is located at the 612th lysine (K612) of the carboxy-terminal viral vRNA binding region of the PB1 protein. ) Is the key site of Susuylation modification. Susuylation modification at this site does not affect the stability and intracellular localization of PB1 protein, but it is very important for the polymerase activity of the virus and its ability to replicate in the cell. Animal studies have found that compared with wild-type viruses, the PB1 protein lysine 612 mutated to arginine (K612R) threoninylation modified-deficient virus in mice has significantly reduced replication titer and virulence. Respiratory droplet transmission between ferrets has decreased. In-depth studies have found that the susuylation defect caused by the K612R mutation significantly reduces the ability of the PB1 protein to bind to the viral vRNA, thereby affecting the transcription and replication of the viral genome.
The research was funded by the National Natural Science Foundation of China, the National Key Research and Development Program, and the Natural Science Foundation of Heilongjiang Province. (Correspondent Deng Yanli)
link to the original text:https://journals.plos.org/plospathogens/article?id=“10.1371/journal.ppat.1009336
Figure 1 Susuhua modified PB1/K612R mutant virus The replication ability and pathogenicity in mice are significantly reduced