Genetics and Functions of Herpes Simplex Virus Type-1 Membrane Proteins UL20/gK in Virion Envelopment and Entry
Doctor of Philosophy (PhD)
Veterinary Medical Sciences - Pathobiological Sciences
The envelopment and egress of the Herpes Simplex Virus is an important event in the life cycle of the virus. The important membrane proteins required for the envelopment and egress of the virus are glycoproteins gM, gK, gE and non-glycosylated membrane proteins UL20p and UL11. Among them one of the most critical protein is the UL20 protein which has four transmembrane domains with amino and carboxyl termini are predicted to lie within the cytoplasmic side of cellular membranes. Studies done in our laboratory have shown that deletion of UL20 or other lethal mutations have an adverse effect on envelopment and results in accumulation of unenveloped capsids in the cytoplasm of infected cells. The carboxyl termini of UL20 protein was shown to be extremely important for viral egress. Mutant viruses were made with mutations in the carboxyl termini of UL20p especially targeting phenylalanine residues as they are known to be an important target for protein-protein interactions through stacking of the aromatic structure. The two membrane proximal phenylalanines were very critical for efficient replication as well as envelopment whereas, the middle phenylalanine at the carboxyl terminus may have a negative effect with regard to the virus since the mutation helped the virus to replicate, envelop and egress better. Another glycoprotein shown to be playing a role in viral entry to susceptible cells or neurons is Glycoprotein K (gK) especially the amino terminus of the protein. If the virus has entered the cell but failed to enter nucleus and start protein synthesis, it is very difficult to assess the entry of virus. In this scenario, the virus may be either stuck at the cell membrane or the transport to the nucleus is adversely affected. In order to demonstrate the entry of virus at a very early time point is quite challenging, but through Proximity Ligation assay (PLA) we have showed the importance of gK, the defect or less efficiency of gK mutant virus in entry to epithelial cultured cells as well as in neurons at a very early time point post infection.
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Charles, Anu Susan, "Genetics and Functions of Herpes Simplex Virus Type-1 Membrane Proteins UL20/gK in Virion Envelopment and Entry" (2014). LSU Doctoral Dissertations. 2619.