New molecular insights into the biology of bunyaviruses

Published on
April 1, 2021

A study by Wageningen Bioveterinary Research (WBVR) uncovered the genome content of individual newly formed bunyavirus particles. Despite the majority of the virus particles do not contain a complete viral genome, these viruses successfully spread within and between their hosts. The study expands our knowledge on the fundamental biology of bunyaviruses, which is crucial for developing timely control strategies such as vaccines and therapies in the event of an outbreak.

Bunyaviruses comprise a large and diverse group of RNA viruses. Most bunyaviruses are transmitted by vectors (mosquitoes, ticks, midges) and some can cause severe disease in animals and humans. Stimulated by climate change, globalization and growing animal and human populations, the risk of bunyavirus outbreaks is increasing. An example of the latent threat was the outbreak caused by the Schmallenberg virus in 2011, originating in Germany and quickly spreading throughout many parts of Europe, affecting livestock farms.

A heterogeneous mixture of bunyavirus particles

The textbook representation of a three-segmented bunyavirus depicts a virus particle containing one molecule of each of its three RNA genome segments (according to their size, named S, M and L). Since these genome segments complement and depend on each other for efficient virus replication, it seems logical to assume that a selective process ensures that a complete set of genome segments is co-packaged into the same virus particle. Using state-of-the-art fluorescence microscopy, researchers at WBVR studied the genomic composition of single virus particles.

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Video: 3D representation of a bunyavirus infected cell. S segment (red spheres), M segment (blue spheres), L segment (yellow spheres), newly formed virus particles (green spheres) and cell nuclei (cyan). Merged spheres show the co-localization of the viral genome segments with the virus particles.

Perhaps counterintuitive, the analysis revealed that the majority of the particles are either empty or incomplete (lacking at least one genome segment), and only few particles are complete (containing the three segments). Interestingly, the proportion of complete particles was found to be higher when the virus replicates in insect cells compared to mammalian cells, supporting the notion that bunyaviruses find their evolutionary origin in insects. 

Translating fundamental knowledge into practice

The fact that bunyaviruses lack a specific mechanism to regulate incorporation of their genome segments into virus particles highlights the flexibility of their genome packaging process. This knowledge has already been put into practice by creating an attenuated Rift Valley fever virus with a genome divided over four segments, instead of three, making it less likely to form particles with a complete set of genome segments. Such live-attenuated viruses are currently being developed as vaccines for veterinary and human use.