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Physiological Role of Nonsense-Mediated Decay in Herpes Simplex Virus Infection and Pathogenicity

Objective

Virus infections cause a major healthcare burden worldwide. The neurotropic human herpes simplex virus 1 (HSV-1) establishes life-long latent infection in neurons, from which it frequently reactivates to disseminate within the population. Clinical complications caused by HSV-1 infections range from mild (herpes labialis) to sight- (keratitis) and even life-threatening diseases (encephalitis). Prevention and treatment of HSV-1 infections are considered a top priority by the WHO. However, development of vaccines and improved therapeutic approaches is hindered by our incomplete understanding of the virus-host interactions that govern infection and disease, especially the interplay between HSV-1 and intrinsic neuronal defenses. The highly conserved cellular RNA degradation pathway nonsense-mediated decay (NMD), which regulates expression of ~10% of cellular transcripts and controls numerous fundamental processes, has recently emerged as an important regulator of neuronal function. Based on my previous postdoctoral studies that revealed a major role for NMD in controlling infection by oncogenic human herpesviruses combined with my preliminary data on HSV-1, I hypothesize that NMD provides an intrinsic defense mechanism that controls HSV-1 infection. In this fellowship, I propose to combine my experience and the expertise of the host institute to determine the physiological relevance and molecular mechanism by which NMD controls HSV-1 infection in its natural human host. Successful completion of my project will lead to improved insight into the virus-host interactions that control infection of HSV-1, thereby providing novel therapeutic targets to combat HSV-1 infection and pathogenesis. Moreover, the extensive and multidisciplinary training in research and transferrable skills provided by this fellowship will be invaluable for my goal of becoming an all-round competitive scientist leading an independent research group focused on intrinsic immunity to neurotropic viruses.

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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

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
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.

€ 203 464,32
Address
DR MOLEWATERPLEIN 40
3015 GD Rotterdam
Netherlands

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Activity type
Higher or Secondary Education Establishments
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Total cost

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