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Creating a comprehensive functional map of the viral and host factors in HCMV infection

Project description

Viral and host factors in HCMV infection

The herpesvirus human cytomegalovirus (HCMV), a type of herpesvirus, is a ubiquitous pathogen infecting much of the world's population. Albeit asymptomatic in most healthy individuals, HCMV can lead to severe congenital disease, morbidity and mortality in immunocompromised adults and during pregnancy. Many fundamental questions about this virus remain poorly understood, including which host and viral factors affect HCMV infection in different cell types. The EU-funded DissectCMV project aims to develop unique tool sets to discover which of these factors regulate the HCMV life cycle. Using high-throughput technologies, researchers will comprehensively characterise the viral elements regulating HCMV progression and the factors determining lytic or latent infection outcome. The resulting screening platform will facilitate dissection and characterisation of HCMV-essential components in any cell type. This work will serve as a paradigm for the study of other herpesviruses and complex host-pathogen interactions.

Objective

The herpesvirus human cytomegalovirus (HCMV), the largest known human virus, is a ubiquitous pathogen that persistently infects the majority of the world's population through the establishment of latency. Although asymptomatic in most healthy individuals, HCMV can lead to a severe congenital disease, as well as morbidity and mortality in immunocompromised adults. Despite the prevalence and pathogenicity of HCMV, many fundamental questions about this pathogen remain open. We still do not know the complete list of functional elements in HCMV's complex genome and how these contribute to infection progression and latency, we do not understand the determinants that govern infection outcome, and we are missing tools that will facilitate systematic dissection of the host and viral factors that are needed for HCMV infection in different cell types.
In this proposal, we suggest to employ our expertise and to develop unique toolsets to shed light on the host and viral factors that regulate the HCMV life cycle. We propose to combine state-of-the art high-throughput tools with mechanistic studies to comprehensively characterize the viral elements that regulate HCMV progression (aim 1), decipher the determinants that dictate infection outcome (lytic vs. latent, aim 2) and develop and implement a sensitive screening platform that will facilitate easy dissection and characterization of HCMV essential components in any cell type (aim 3).
The knowledge generated from these objectives will provide a clearer depiction of the different determinants that control HCMV infection and will generate new tools for the benefit of the community. These in turn could help to expand our therapeutic options. More broadly, with its comprehensive and complementary approaches, this work will provide a paradigm for the study of other herpesviruses and for understanding complex host-pathogen interactions.

Host institution

WEIZMANN INSTITUTE OF SCIENCE
Net EU contribution
€ 2 000 000,00
Address
HERZL STREET 234
7610001 Rehovot
Israel

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Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 2 000 000,00

Beneficiaries (1)