关键词: 流感病毒, 基因元件, 减毒策略, 条件响应, 减毒活疫苗, 溶瘤病毒

Abstract:

Influenza viruses are highly variable and transmissible, and their infections can cause infectious respiratory diseases, such as seasonal influenza outbreaks around the world, one of the most serious public health problems at present, which can be prevented by influenza vaccination. The genome sequences, protein structures and functions of influenza viruses, as well as their packaging mechanisms are relatively clear. they are also important models, which can be used for developing conditional control genetic elements and the construction of intelligent responsive viruses. With the development of reverse genetics and synthetic biology technology, influenza viruses that are genetically engineered can better control virus replication to improve the safety of vaccines, and induce strong immune responses in human being, which have attracted wide attention in tumor immunotherapy. Several studies using simple or modified influenza viruses for treating liver cancer, melanoma, or lung cancer have found breakthroughs. In this paper, three novel strategies for attenuating influenza viruses, namely, proteolytic targeted chimeric virus, conditionally replicating influenza-attenuated live virus and highly interferon-sensitive virus, are described. The oncolytic effects of influenza viruses encoding premature stop codon chimeric antigen peptide, influenza viruses recombining with PD-L1 or CTLA4 immune checkpoint and influenza viruses expressing GM-CSF with truncated NS1 fragment on melanoma and hepatocellular carcinoma are reviewed, respectively, which suggest that the influenza viruses can be used as a live attenuated vaccine and a potential carrier for oncolytic viruses, and future researchers can be focused on constructing influenza viruses with more innovative strategies and different viruses to build a live attenuated vaccine and oncolytic viruses, in order to obtain high safety and more clinical curative treatment, improving the life quality of the patients. {L-End}

Key words: influenza viruses, genetic parts, attenuation strategies, conditional responses, attenuated live vaccines, oncolytic viruses