Rational approaches for attenuation of a segmented genome RNA virus

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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.