رسالة جامعية
Mechanisms of cell adhesion regulation by herpes simplex virus
| العنوان: | Mechanisms of cell adhesion regulation by herpes simplex virus |
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| المؤلفون: | Barrow, Henry |
| بيانات النشر: | University of Cambridge Department of Pathology Jesus College |
| سنة النشر: | 2023 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Cell adhesion, Focal adhesion, Herpes simplex virus, Integrin-linked kinase, pUL21, pUL7:pUL51, Virology |
| الوصف: | Herpes simplex virus (HSV)-1 is a highly prevalent human pathogen that establishes a life-long infection. HSV-1 promotes its replication and spread by expressing multi-functional proteins that extensively remodel the host cell. Three such proteins are pUL21, pUL7 and pUL51. pUL21 is a viral phosphatase adapter. pUL7 and pUL51 form a complex that localises to juxtanuclear membranes and sites of cell-matrix adhesion termed focal adhesions. All three proteins are required for efficient virus assembly, egress and cell-to-cell spread. However, the viral or cellular binding partners required for these functions have not yet been fully identified. Furthermore, very little is known about how the interactions of pUL7:pUL51 at focal adhesions promote virus replication, spread or survival. Biotin-proximity ligation (BioID) was used to identify novel viral and cellular protein interaction partners for pUL21 and pUL7:pUL51. The IPP complex, which consists of integrin-linked kinase (ILK), PINCH and parvin, was identified as a potential interaction partner for pUL7:pUL51 at focal adhesions. Colocalisation and a direct interaction was confirmed using immunofluorescence microscopy and biochemical approaches respectively, with binding between pUL51 and ILK identified as primarily responsible for the interaction. Expression of pUL7:pUL51 was shown to alter focal adhesion morphology and be important for preventing infected cell rounding and detachment. Cell lines recombinantly expressing pUL7:pUL51 showed that the complex directly alters cell adhesion dynamics by likely preventing focal adhesion disassembly. pUL7:pUL51 could not localise to focal adhesions and prevent cell rounding in the absence of ILK, confirming the importance of this interaction for function. However, no large defect in cell-to-cell spread was observed in the absence of ILK, suggesting this is not a mechanism by which pUL7:pUL51 promotes virus spread between cells. When performing the BioID experiments it was observed that fusion of the biotin ligase to pUL7 ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/363430Test; https://doi.org/10.17863/CAM.105503Test |
| DOI: | 10.17863/CAM.105503 |
| الإتاحة: | https://doi.org/10.17863/CAM.105503Test https://www.repository.cam.ac.uk/handle/1810/363430Test |
| حقوق: | All Rights Reserved ; https://www.rioxx.net/licenses/all-rights-reservedTest/ |
| رقم الانضمام: | edsbas.6AE81838 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.105503 |
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