Bunyaviruses—a family that includes the deadly Crimean-Congo haemorrhagic fever virus—kill the vertebrate cells they infect but leave mosquito cells unharmed, and researchers want to know why. This matters because bunyaviruses cause severe disease in humans and livestock, yet no licensed vaccines or specific treatments exist for most of them. The viruses replicate efficiently in both insect and mammalian hosts, but the molecular details that determine whether a cell lives or dies remain unknown. Understanding this difference could reveal new ways to block the virus in humans without harming healthy cells. If successful, the project will map the full replication cycle in both cell types, solve the 3D structures of key viral proteins, and identify which mosquito defence molecules—such as small RNAs—control persistent infection. The work is fundamentally curiosity-driven: it asks how a single virus produces two completely different outcomes depending on the host. That knowledge could eventually guide the design of live attenuated vaccines or antiviral drugs that exploit the virus’s own weaknesses, but no immediate clinical application is expected.
View original technical description
Like other groups of arboviruses, the transmission cycle of bunyaviruses involves replication in a blood-feeding arthropod and a vertebrate host. In both hosts the viruses replicate efficiently but with fundamentally different outcomes for the cell: nonlytic in invertebrate cells leading to a persistent infection versus lytic in vertebrate cells leading to cell death. The family includes a number of pathogens of clinical and veterinary significance as well as recently emerged viruses. Our ultima te aim is to understand the intimate molecular details of virus replication in these disparate cell types that account for the different outcomes of infection using a multidisciplinary approach, and selected important representative viruses. Key goals include: to achieve a complete understanding of the roles of virus components in the replication cycles in both vertebrate and invertebrate cells; to use state-of- the-art microscopical techniques to monitor virus replication in real-time; to determine the structures of selected bunyavirus proteins; to determine the roles of genomic noncoding sequences in viral replication; to obtain a detailed picture of viral RNA transcripts produced during infection; to exploit reverse genetics to engineer attenuated viruses with potential as vaccines; to understand how different bunyaviruses can overcome host defence mechanisms in both vertebrate and invertebrate cells; to identify interferon stimulated gene-products that inhibit bunyavirus replication and determine their mode of action to determine the biogenesis and role of small RNAs produced in infected mosquito cells during acute and persistent infections.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know