Rational approaches for attenuation of a segmented genome RNA virus

疫苗是预防疾病的最有效手段之一。关于被杀死的病毒疾病和活疫苗，可用于预防和控制一些人和动物的病毒感染，但对于相当数量的疾病，特别是由新出现的病毒引起的疾病，尚未开发出疫苗。活疫苗包括降低致病能力的改良型病毒，即它们被减毒。减毒活疫苗的一个优点是它们能诱导复杂的免疫反应，模仿真实感染的免疫反应。减毒活病毒的潜在缺点包括在一些接受者(例如，免疫受损的人)中可能患病，与灭活的疫苗相比更不稳定，以及疫苗的变化导致病毒的致病能力恢复。此外，减毒病毒有可能与流行的野生型或密切相关的毒株相互作用，也导致毒力恢复。对于遗传信息分离在不同片段上的病毒，如流感病毒，这可能是由于双重感染细胞中的基因组片段混合(重新排序)，导致后代病毒的片段分别来自两个亲本病毒。该项目的目的是通过重组DNA技术操纵模型节段基因组病毒Bunyamwera病毒的基因组，以产生无法与另一种病毒株重新配对的减毒病毒。原则证明可能导致开发更安全的节段性基因组病毒减毒活疫苗。

Vaccines are among the most effective means to preventing diseases. With regard to viral diseases both killed and live vaccines are available to prevent and control a number of human and animal viral infections, though for a significant number of diseases, particularly those caused by emerging viruses, no vaccines have yet been developed. Live vaccines comprise modified viruses that have reduced capacity to cause disease i.e. they are attenuated. An advantage of live-attenuated vaccines is that they induce complex immune responses that mimic those of an authentic infection. Potential disadvantages of live-attenuated viruses include the possibility of disease in some recipients (e.g. the immunocompromised), greater instability compared to killed vaccines, and changes to the vaccine that result in restoration of the disease-causing ability of the virus. In addition, there is the possibility for the attenuated virus to interact with circulating wild type, or closely related, strains, also resulting in restoration of virulence. For viruses which have their genetic information separated on different segments, such as influenza virus, this could occur by mixing (reassortment) of genome segments in dually infected cells, resulting in progeny viruses with segments derived from each the two parent viruses. The aim of this project is to manipulate the genome of a model segmented genome virus, Bunyamwera virus, by recombinant DNA techniques, to produce an attenuated virus that is unable to reassort with another viral strain. Proof-of-principle could lead to the development of safer live attenuated vaccines for segmented genome viruses.