A graphical abstract showing development of an Aedes aegypti cell line which stably expresses Zika virus (ZIKV) capsid proteins in order to study virus-vector protein-protein interactions through quantitative label-free proteomics

New research by the Centre for Virus Research's Kohl Lab shows that the Zika virus (ZIKV) capsid interacts with several mosquito protein pathways, revealing pro-viral host factors critical for establishing infection in mosquito cells.

ZIKV is an arbovirus of the Flaviviridae family originally isolated from a Rhesus monkey in Uganda in 1947.

Though previously limited to Africa and Southeast Asia, outbreaks across Pacific Ocean islands were detected throughout 2013–2014.

ZIKV infection is associated with mild and unspecific disease manifestations but has also been linked to serious complications including Guillain-Barré syndrome and congenital Zika syndrome.

The escalating global prevalence of arboviral diseases emphasises the need to improve our understanding of their biology, but research in this area has been hindered by the lack of molecular tools for studying virus-mosquito interactions.

Currently, no drugs or vaccines against ZIKV are available, which enforces the need for complementary vector research in mosquito cells to better understand its replication, transmission, and interaction with cellular protein.

In this study, published in Nature Communications, CVR scientists developed an Aedes aegypti cell line that stably expresses ZIKV capsid proteins in order to examine virus-vector protein-protein interactions.

Through quantitative label-free proteomics, they show that ZIKV capsid interacts with several mosquito protein pathways in our stable cell line system.

ZIKV utilises TER94 and the ubiquitin-proteasome pathway during early stages of infection by interacting with the capsid protein in mosquito cells. Interestingly, in human cells, ZIKV subverts VCP, the human ortholog of TER94, in a similar manner.

This research also shows that TER94/VCP potentially uses UBR5 (E3 ubiquitin ligase) as a co-factor during this interaction with ZIKV capsid.

The conserved infection mechanism of ZIKV sheds light on how arboviruses hijack cellular machineries across divergent host species (mosquitoes vs humans).

Rommel Gestuveo, PhD student in the Kohl Lab and first author, said: "Our findings in the paper builds up on the previous work conducted in our lab to study mosquito vectors and their viruses using different cell lines.

"Developing such a stable mosquito cell line system is important in studying not only ZIKV but also other mosquito-borne viruses and overall mosquito biology that continue to affect global public health."

Analysis of Zika virus capsid-Aedes aegypti mosquito interactome reveals pro-viral host factors critical for establishing infection

  • Rommel J. Gestuveo, Jamie Royle, Claire L. Donald, Douglas J. Lamont, Edward C. Hutchinson, Andres Merits, Alain Kohl & Margus Varjak
  • Nature Communications volume 12, Article number: 2766 (2021) 

First published: 24 May 2021

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