The conserved Herpesviridae protein kinase (CHPK) of Gallid alphaherpesvirus 3 (GaHV3) is required for horizontal spread and natural infection in chickens

Authors: KRIETER, ANDREA - University Of Illinois; XU, HUAI - University Of Illinois; AKBAR, HAJI - University Of Illinois; Kim, Taejoong; JAROSINISKI, KEITH - University Of Illinois

Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/9/2022
Publication Date: 3/12/2022
Citation: Krieter, A., Xu, H., Akbar, H., Kim, T.N., Jarosiniski, K.W. 2022. The conserved Herpesviridae protein kinase (CHPK) of Gallid alphaherpesvirus 3 (GaHV3) is required for horizontal spread and natural infection in chickens. Viruses. 14(3):586. https://doi.org/10.3390/v14030586.
DOI: https://doi.org/10.3390/v14030586

Interpretive Summary: Marek’s disease (MD) is a highly infectious lymphoproliferative disease of chicken, and MD is an economically important disease affecting the poultry industry. Current MD vaccines can reduce the MD clinical symptoms but do not efficiently block the virus infection. The conserved herpesvirus protein kinase (CHPK) of Marek’s disease virus (MDV) is required for the virus spread from chicken to chicken, and we hypothesized other CHPKs are also required for the virus spread in birds. Using recombinant 301B/1 virus can track the virus replication in the host, the CHPK activity of 301B/1 virus was successfully changed and the kinase defected 301B/1 virus failed to spread the virus in a natural infection model. To confirm the importance of CHPK, the CHPK activity was restored resulting in successful spread of 301B/1 from chicken to chicken. The results indicate that CHPK of 301B/1 is also required in virus spread between chickens in experimental and natural infection model. These data strongly suggest that the essential function of CHPK is conserved, and this knowledge can be exploited during the generation of future vaccines against MD that affects the poultry industry worldwide.

Technical Abstract: We have formerly identified the conserved herpesvirus protein kinase (CHPK) as essential for horizontal transmission of Marek’s disease virus (MDV). Thus far, it has been confirmed that the mutation of the invariant lysine (K) of CHPKs abrogates kinase activity and that CHPK activity is required for MDV horizontal transmission. Since CHPK is conserved among all members of the Herpesviridae, we hypothesized that CHPK, and specifically its kinase activity, is important for the horizontal transmission of other herpesviruses. To test this hypothesis, we utilized our experimental and natural infection model in chickens with MD vaccine strain 301B/1 of Gallid alphaherpesvirus 3 (GaHV3). First, we mutated the invariant lysine (K) 157 of 301B/1 CHPK to alanine (A) and determined whether it was required for horizontal transmission. To confirm the requirement of 301B/1 CHPK activity for transmission, a rescued virus was generated in which the A157 was changed back to a K (A157K). Despite both the CHPK mutant (K157A) and rescuant (A157K) viruses having replication defects in vivo, only the CHPK mutant (K157A) was unable to spread to contact chickens, while both wild-type and rescuant (A157K) viruses transmitted efficiently, confirming the importance of CHPK activity for horizontal spread. The data confirm that CHPK is required for GaHV3 transmission and suggest that the requirement of avian CHPKs for natural infection is conserved.