Illuminating the enteroviral life cycle

Introduction

Enteroviruses are highly prevalent pathogens that have enormous clinical and socio-economic impact. Well-known examples are poliovirus, coxsackievirus, enterovirus-A71, enterovirus-D68, and rhinovirus. Although important insights have been obtained in the enteroviral life cycle, many important questions remain unanswered due to shortcomings of current imaging and biochemical methodologies. There is a high need for novel technologies that allow sensitive and real-time observation of the dynamics and localisation of viral RNA, viral proteins, and host factors at the single-cell level.

Long-term Goals

My long-term goal is to understand enterovirus replication and translate knowledge into the development of antiviral drugs. My lab has a long-standing track record and has made many important contributions to understanding the molecular mechanisms of enterovirus replication and the formation of viral replication organelles. Recently, we constructed a reporter virus that in combination with high-resolution microscopy allowed for the first time to visualize translation, and the regulation thereof, of single (entero)viral RNAs in living cells.

Project Goals

The goal of this project is to visualize and dissect the spatial and temporal regulation of different phases of the enterovirus life cycle.

First Steps

As a first step, novel recombinant reporter viruses for application in real-time imaging technologies will be developed. These viruses will be used to study:

1. Viral RNA replication
2. Virus assembly
3. Pre-lytic virus release in living cells

Moreover, they will be instrumental in studying the structure and composition of the viral replication organelles and the associated replication complexes through advanced cryo-electron microscopy and tomography technologies, and proteomics/lipidomics analysis, respectively.

Expected Outcomes

This project will lead to important new insights into the molecular interplay between enteroviruses and their hosts, which is essential for developing urgently needed antiviral drugs.