Live Triple Gene-Deleted Pseudorabies Virus-Vectored Subunit PCV2b and CSFV Vaccine Undergoes an Abortive Replication Cycle in the TG Neurons following Latency Reactivation
Author:
Pavulraj Selvaraj1ORCID, Stout Rhett W.1ORCID, Paulsen Daniel B.1, Chowdhury Shafiqul I.1ORCID
Affiliation:
1. Department of Pathobiological Sciences and Louisiana Animal Disease Diagnostic Laboratory, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
Abstract
Like other alpha herpesviruses, pseudorabies virus (PRV) establishes lifelong latency in trigeminal ganglionic (TG) neurons. Upon stress, the latent viruses in the TG neurons reactivate and are transported anterograde from the neuron cell bodies to the nerve endings in the nasal mucosa, where they replicate and are discharged in the nasal and oral secretions. Consequently, the virus is transmitted to other naïve animals. This cycle of latency and reactivation continues until the animal dies or is slaughtered. We have constructed a PRV triple mutant virus (PRVtmv) and used it as a live subunit vaccine vector against porcine circovirus 2b (PCV2b) and classical swine fever virus (CSFV) (PRVtmv+). We compared the latency reactivation properties of PRVtmv+ with its parent wild-type (wt) Becker strain following intranasal infection. The results showed that PRV wt and PRVtmv+ established latency in the TG neurons. Based on nasal virus shedding, immediate early (infected cell protein 0; ICP0) and late genes, MCP (major capsid protein) and gC (glycoprotein C) transcriptions, and viral DNA copy numbers in the TGs of latently infected and dexamethasone (Dex)-treated pigs, both PRV wt and PRVtmv+ reactivated from latency. We noticed that PRV wt virus replicated productively in the terminally differentiated, postmitotic TG neurons, but PRVtmv+ failed to replicate and, therefore, there was no virus production in the TG. In addition, we found that only the PRV wt virus was shed in the nasal secretions following the Dex-induced reactivation. Our results demonstrated that the PRVtmv+ is safe as a live viral subunit vaccine vector without the possibility of productive replication in the TG upon reactivation from latency and without subsequent nasal virus shedding. This property of PRVtmv+ precludes the possibility of vaccine virus circulation in pigs and the risk of reversion to virulence.
Subject
Virology,Infectious Diseases
Reference29 articles.
1. Pavulraj, S., Pannhorst, K., Stout, R.W., Paulsen, D.B., Carossino, M., Meyer, D., Becher, P., and Chowdhury, S.I. (2022). A Triple Gene-Deleted Pseudorabies Virus-Vectored Subunit PCV2b and CSFV Vaccine Protects Pigs against PCV2b Challenge and Induces Serum Neutralizing Antibody Response against CSFV. Vaccines, 10. 2. Economic impact of an epizootic of pseudorabies in a commercial swine herd in Ohio, achieving test negative status and quarantine release by use of vaccination and test and removal;Miller;J. Am. Vet. Med. Assoc.,1992 3. Investigation of sites of pseudorabies virus latency, using polymerase chain reaction;Wheeler;Am. J. Vet. Res.,1991 4. Deng, J., Wu, Z., Liu, J., Ji, Q., and Ju, C. (2022). The Role of Latency-Associated Transcripts in the Latent Infection of Pseudorabies Virus. Viruses, 14. 5. Chen, J., Li, G., Wan, C., Li, Y., Peng, L., Fang, R., Peng, Y., and Ye, C. (2022). A Comparison of Pseudorabies Virus Latency to Other alpha-Herpesvirinae Subfamily Members. Viruses, 14.
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|