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Characterization of naturally occurring flavivirus host-specific mutations

15 February 2024

About speaker

Liu Ruyue

Ruyue Liu is a PhD student from the Department of Pharmacy, National University of Singapore. She has been working under the supervision of Dr. October M. Sessions since 2020, with a focus on the interface between flavivirus adaptation and host immune response. This incorporates the characterization of naturally occurring flavivirus host-specific mutations from a Zika outbreak in Nicaragua, as well as deciphering a single-cell resolution human immune landscape against yellow fever and Japanese encephalitis through a controlled human sequential infection model.


Abstract

In 2016, Zika virus (ZIKV) infected millions with instances of neurological and congenital complications. ZIKV, like most RNA viruses, has an error-prone RNA-dependent RNA polymerase (RdRp) leading to numerous mutations over a single infection. Herein, we identified common intrahost mutations from Nicaragua during the epidemic. They were evaluated for replicative potential and three exhibited growth advantages. We then examined the underlying mechanisms by cellular transcriptomics, namely immunological and physiological disturbance. Lastly, we illustrated their ability to change the growth phenotypes of the closely related dengue virus (DENV). Together, we demonstrated the enormous potential of intrahost microevolution with single-point conversions.


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