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Imprint
Structure-Function Analysis of Herpesvirus Glycoprotein H
Project
Project code: FLI-IMVZ-08-Ri-0490
Contract period: 01.07.2016
- 31.07.2020
Purpose of research: Experimental development
Herpesviruses infect cells using a machinery consisting of receptor-binding components and the fusion-inducing complex. Whereas receptor-binding involves primarily subfamily-specific proteins, such as alphaherpesvirus glycoprotein D, proteins involved in fusion between virion envelope and cellular plasma membrane are conserved throughout the Herpesviridae indicating a common mechanism of penetration. These include glycoprotein B whose structure is similar to that of the fusogenic G protein of vesicular stomatitis virus, and a heterodimeric complex of glycoproteins H and L. Although the crystal structure of gH proteins of three herpesviruses has been solved, no immediate revelation of its function was apparent. We elucidated the structure of a core fragment of gH of the alphaherpesvirus pseudorabies virus (PrV). Based on structural predictions we now want to perform site-directed mutagenesis to analyze the contribution of different regions of gH to fusion including a predicted mobile ‘flap’ region which may shield or expose a hydrophobic surface, and a syntaxin-like bundle. Construction of chimeric gH molecules between PrV and HSV-1 is envisaged following the uncovered four-domain structure of gH. In a second approach we want to build on previous work from our lab and assess the role of gL in gH maturation and function. In contrast to other gH homologs, PrV gH does not require gL for intracellular transport and virion incorporation, although gL augments gH function. gL is not strictly required for PrV infectivity, allowing us to perform reversion analysis with a gL-negative PrV mutant. This approach already yielded a striking result with compensation of gL-deficiency by a naturally formed chimeric gDH protein. We want to extend these studies with more independent passages to uncover additional compensatory mutations which should also help in understanding gH/gL function and provide insight into the complicated fusion mechanism used by herpesviruses.
Section overview
Subjects
- Animal health
- Biotechnology
Framework programme
Funding programme
Excutive institution
FLI - Institute of Molecular Virology and Cell Biology (FLI - IMVZ)
