New strategies for engineering influenza viruses and their applications

doi:10.12211/2096-8280.2023-078

Abstract

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

摘要：

流感病毒有着极强的变异性和传播性，常在全球范围内引起季节性的流感爆发。流感病毒的基因组序列、蛋白结构与功能、病毒的包装机制等环节研究相对清楚，也是一种重要的模式病毒，用于条件控制基因元件的发现和确证，构建智能响应型病毒等。随着反向遗传学与合成生物学的发展，通过基因工程改造的流感病毒能更好地控制病毒复制来提高疫苗的安全性，以及诱发机体产生强烈的免疫反应，在肿瘤免疫治疗领域引发广泛关注。本文描述了蛋白质水解靶向嵌合病毒、条件复制型流感减毒活病毒和高干扰素敏感病毒等三种新型减毒流感病毒改造策略，并对编码过早终止密码子的嵌合抗原肽的流感病毒、与PD-L1或CTLA4免疫检查点重组的流感病毒、截短的NS1片段表达GM-CSF的流感病毒分别对黑色素瘤、肝癌的溶瘤作用进行评述。未来，将通过创新性地运用不同策略、不同病毒来构建减毒活疫苗和溶瘤病毒，以便在临床上获得更加安全有效的治疗手段。

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

CLC Number:

R915

Xiya GUO, Ji CHEN, Mingxin DONG. New strategies for engineering influenza viruses and their applications[J]. Synthetic Biology Journal, 2024, 5(2): 267-280.

郭茜亚, 陈积, 董铭心. 流感病毒改造新策略及其应用[J]. 合成生物学, 2024, 5(2): 267-280.

Figures/Tables 4

Fig. 1 Production of the PROTAC virus and its response in mice/ferrets

Fig. 2 Production of the 4-HT-dependent virus and its in vitro and in vivo responses

Fig. 3 Effectiveness of engineered influenza viruses on the pulmonary metastatic melanoma

Fig. 4 Modifications of influenza viruses and their effectiveness on the hepatocellular carcinoma

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