Determining the role of the conserved Herpesviridae protein kinase (CHPK) in replication and transmission of avian herpesviruses

Krieter, Andy

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https://hdl.handle.net/2142/120228 Copy

Description

Title

Determining the role of the conserved Herpesviridae protein kinase (CHPK) in replication and transmission of avian herpesviruses

Author(s)

Krieter, Andy

Issue Date

2023-04-07

Director of Research (if dissertation) or Advisor (if thesis)

Jarosinski, Keith W

Doctoral Committee Chair(s)

Jarosinski, Keith W

Committee Member(s)

• Yoo, Dongwan
• Maddox, Carol
• Steelman, Andrew J

Department of Study

Pathobiology

Discipline

VMS - Pathobiology

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Avian herpesvirus
• CHPK
• Marek's disease
• vaccine
• protein kinase

Abstract

Marek’s disease (MD) is a devastating disease in the poultry industry caused by an oncogenic herpesvirus called Marek’s disease virus (MDV). Current vaccination strategies are not protective enough to induce sterilizing immunity, nor block transmission, which has driven MDV to increased virulence and transmission. Better strategies are needed to block MDV circulation in poultry houses by targeting transmission. The conserved Herpesviridae protein kinase (CHPK) is a gene encoded by all members of Herpesviridae. This gene is essential for dissemination of the virus, and for beta- and gammaherpesviruses it is also essential for replication of the virus. However, for avian alphaherpesviruses it is not essential for replication. Our previous work has shown that MDV CHPK, gene UL13, is essential for transmission of the virus, but is dispensable for both in vitro and in vivo replication. For other CHPKs, they have been shown to be important for both virion assembly in infected cells and virion disassembly in newly infected cells. Thus, we hypothesize that MDV CHPK plays a role in both release of infectious virus from the infected chickens and initiation of infection in the naïve chicken. The research described in this thesis provides insight into the stability of CHPK protein, the conserved function(s) of CHPK in avian herpesviruses, CHPK’s ability to undergo functional complementation, and patterns of cellular localization of avian CHPKs. First, we determined that the invariant lysine 170 (K170) of MDV CHPK is required for interindividual spread, auto phosphorylation of CHPK, and mutation to methionine (M170) results in instability of the CHPK protein. Mutation of CHPK severely affected CHPK localization and late viral protein expression in feather follicles where MDV is shed. Second, we investigated CHPK and its importance in MD vaccine Gallid alphaherpesvirus 3 (GaHV3), replication and transmission; mutated CHPK rendered GaHV3 unable to transmit while wild type GaHV3 transmitted successfully. Third, coinfection of vaccine and virulent MDV was studied; our results showed dual infection and complementation successfully occurred but was not mediated by CHPK. Fourth, we confirmed that the invariant lysine of GaHV3 CHPK is required for interindividual spread and this mutation severely affected CHPK localization and late gene expression in GaHV3. In summary, these studies advance our knowledge of avian herpesvirus pathogenesis, the conserved role of avian CHPKs in host-to-host transmission and potentiate the use of non-transmittable MD vaccines in the future.

Graduation Semester

2023-05

Type of Resource

Thesis

Copyright and License Information

Copyright 2023 Andy Krieter

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