Active Infection & Immunity Genetics & Molecular Biology

RNA-communication between arboviruses and their hosts

In plain English

AI plain-English summary

Zika and yellow fever viruses may be folding their RNA genomes differently inside human cells than inside the mosquito cells that carry them, and those differences could help the viruses jump between species. The problem is that flaviviruses—which also include dengue—cause severe disease and death worldwide, yet scientists do not know whether the viral RNA physically interacts with the host’s own RNA, or whether those interactions change depending on whether the host is a human or an arthropod. This project uses a method called COMRADES to map exactly where and how viral RNA base-pairs with host RNA in both cell types. If the research succeeds, it could reveal a new mechanism viruses use to enhance replication and disease. That would open the door to antiviral drugs that disrupt host-virus RNA interactions rather than targeting viral proteins—a fundamentally different strategy. The work is primarily fundamental science: it asks how RNA folding and base-pairing shape zoonotic transmission. But understanding that process could eventually inform efforts to predict or block future viral jumps from insects to humans.

View original technical description
Flaviviruses such as Zika virus, dengue virus and yellow fever virus transmit their RNA genomes between arthropods and humans, causing widespread pathology and death. During infection, the viral RNA genome resides inside the host cells’ cytoplasm. However, whether the viral genome folds differently inside human and arthropod cells, and whether it interacts with the hosts’ own RNA remain largely unexplored. The aim of this proposal is to dissect the dynamics and function of the flaviviral RNA interactome. I will employ my recent developed COMRADES method to investigate the base pairing capacity and function of two related flaviviruses: Zika virus and yellow fever virus, and to address the following little-explored aspects in their biology: (i) Do viral genomes base-pair with host RNAs? What are the roles of host-virus RNA base-pairing? (ii) Do viral genomes base-pair differently inside different hosts? What are the functional implications? The results will cast light on how RNA viruses utilise RNA base-pairing to enhance their replication and pathogenicity; offer new opportunities to develop antiviral therapeutics targeting the host-virus RNA-RNA interactome; and establish a new role for RNA base-paring in zoonosis.

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Researchers

Omer Ziv (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Mechanism of cell-to-cell transmission of flaviviruses
From genes to symbionts: arbovirus-vector interactions
Mechanistic analysis of RNA-replication elements involved in early stages of chikungunya virus replication.
Rethinking the landscape of host defences against emerging viruses
22BBSRC-NSF/BIO: Deciphering the RNA structure code for viroid infections

Original classification

Sir Henry Dale Fellowship

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