Title page for ETD etd-04262012-000830


Type of Document Dissertation
Author David, Andrew Timothy
Author's Email Address adavid8@tigers.lsu.edu
URN etd-04262012-000830
Title The Role of Glycoprotein K (gK) in the Ocular and Neuropathogenesis of Herpes Simplex Virus-Type 1 (HSV-1)
Degree Doctor of Philosophy (Ph.D.)
Department Pathobiological Sciences (Veterinary Medical Sciences)
Advisory Committee
Advisor Name Title
Kousoulas, Konstantin G. Committee Chair
Paulsen, Daniel B. Committee Member
Sehgal, Inder Committee Member
Wakamatsu, Nobuku Committee Member
Constant, W. David Dean's Representative
Keywords
  • Herpes simplex virus
  • glycoprotein K
  • pathogenesis
  • neural
  • eye
  • neuron
  • ocular
  • HSV
Date of Defense 2012-04-17
Availability unrestricted
Abstract
Herpes simplex virus type 1 (HSV-1) is a DNA virus that is a ubiquitous pathogen of humans. The hallmark of the HSV-lifecycle is infection of a mucosal surface with spread to sensory neurons where the virus establishes a latent infection with periodic recurrences for the life of the host. The most common course of symptomatic disease with HSV-1 is the typical mucocutaneous lesion that is self-limiting. HSV-1 can also cause acute encephalitis and ocular pathology on reactivation. Both of these manifestations of the disease have severe consequences. Although ocular infection is less frequent, the extensive prevalence of HSV makes it one of the most common infectious causes of blindness in developed countries. Herpetic encephalitis causes significant morbidity and mortality, particularly in the immunosuppressed or untreated individual. HSV-1 specifies at least 11 glycoproteins that are expressed in the infected cells. The viral glycoproteins are the first interface of the virus with a host cell and are therefore vitally important to virus pathogenesis. Glycoproteins B, C, D, H, and L have been extensively studied and found to be involved in initial attachment, fusion, and entry of the virus into a host cell. Recent work in this laboratory has shown that glycoprotein K (gK) is also involved in the fusion machinery of the virus, however, little was known about the role of gK in the pathogenesis of the virus. To assess the role of gK in pathogenesis, mutant viruses were used an experimental infection in a mouse eye model. In this investigation, gK was found to have a critical role in the pathogenesis of the virus in the eye as well as in spread of the infection to neurons and subsequent development of latency. Following this work, a primary neuronal culture system was established to further define the role that gK played in neuronal infection and transport. Using this system, gK was found to be a critical determinant for neuronal transport and pathology. Since gK deficient viruses appear unable to infect neurons, defining this phenotype may assist in the eventual development of a successful vaccine strain of the virus.

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