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Spatial arrangement and interactions of HSV-1 cell entry associated proteins on the native viral envelope

Project description

Dissecting herpesvirus cell entry

Herpesviruses are DNA viruses that cause highly prevalent and lifelong infections which pose a significant medical challenge. To prevent herpesvirus-associated disease, there is an imminent need for novel antiviral drugs. Funded by the Marie Skłodowska-Curie Actions programme, the HSV1ENTRYPROTEINMAP project aims to investigate the mechanism of herpesvirus entry into cells. Researchers will employ a multidisciplinary approach to delineate the arrangement of viral glycoproteins and their interaction with cellular partners to mediate viral envelope fusion with the cell membrane. Results will help address herpesvirus transmission and possibly facilitate the design of vaccines.

Objective

Herpesviruses are a family of large, complex, DNA viruses that are highly prevalent across the global human population, causing life-long infections and cycle between latent and active disease. The severity of diseases caused by this viral family ranges from cold sores, genital ulcers and blisters to blindness, meningitis, cancer, and congenital defects. Herpesviruses present a significant public health concern due to high prevalence, ease of transmission, severity of associated diseases, lack of vaccines for most species, and toxicity of available medical interventions. There remains a pressing requirement to develop novel antiviral drugs to prevent diseases associated with Herpesvirus infections. Entry of HSV-1, the focus of the proposed research, is dependent on membrane fusion mediated by virally encoded glycoproteins gB, gD, gH, and gL found on the viral envelope. Although all four glycoproteins are known to be necessary for membrane fusion, the molecular details and stoichiometry of the interactions as well as how the interactions regulate or influence the fusion process remains unknown. The proposed project aims to uncover the spatial arrangement and interactions of the HSV-1 cell entry proteins. I will employ a multidisciplinary approach combining methods and data from structural biology, biochemistry as well as biophysics to solve the mechanistic details of a virology question. The proposed research is highly innovative as it is designed to push current technological barriers by taking advantage of recent methodological advances to answer specific key biological questions in herpesvirus entry. I will determine at molecular resolution, the spatial arrangement and temporal interactions between essential entry proteins required at the onset of the HSV-1 infection. This project has the potential to unveil the detailed mechanism of action of viral glycoproteins in their native environment that ultimately lead to HSV-1 fusion.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2021-PF-01

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Coordinator

UNIVERSITY OF HAMBURG
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 173 847,36
Address
MITTELWEG 177
20148 Hamburg
Germany

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Region
Hamburg Hamburg Hamburg
Activity type
Higher or Secondary Education Establishments
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Total cost

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