Anticipating viral zoonoses from arthropod reservoirs

Emerging zoonotic viruses often undergo a process of host adaptation to expand either their vector host range or their ability to infect human hosts.

Adaptations to better utilize host species receptors for attachment are particularly common, although downstream adaptations are also important and lipid trafficking adaptations that may function in entry have been shown critical in the recent emergence of Chikungunya virus.

Here, we develop and exploit a technology for synthetic attachment factors to study viruses that cannot yet bind cells of a particular species or tissue type with high affinity.

This technology makes it possible to study downstream host restriction factors in advance of viral emergence and without gain-of-function experiments.

We will use this to develop a parallel assay for multiple alphaviruses and flaviviruses to better understand the role of attachment factors in host and tissue specificity as well as to develop paired CRISPR screens to definitively assign host factors as affecting attachment or downstream processes.

The knowledge thus gained will be important in risk assessment and surveillance for novel and emerging zoonotic viruses.