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Genetic and pathogenic characterization of classical swine fever virus LOM strains isolates from Jeju island

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Alternative Title
돼지열병 바이러스 LOM 제주 야외주의 유전학적 특성 및 병원성 연구
Abstract
Chapter 1. Genotypic characterization of classical swine fever (CSF) virus LOM field isolates from Jeju island

After the unintentional vaccination of the LOM vaccine strain in 2014, classical swine fever virus (CSFV) reemerged in naïve pig herds on Jeju Island, South Korea, which had been a CSF-free region with a non-vaccination policy for a decade. Since the re-emergence, endemic outbreaks of CSFV have occurred in Jeju, causing enormous damage to provincial pig farms. The present study reports the complete genome sequences and molecular characterization of the LOM-derived field CSFV strains responsible for the current outbreaks on Jeju Island. The emergent Jeju LOM-derived isolates shared 98.9–99.7% and 98.7–99.0% nucleotide sequence identity at the E2-gene and whole-genome levels compared to the LOM vaccine strain, respectively. Genetic and phylogenetic analyses indicated that the CSFV field isolates were closest to the LOM strains, but appeared to have undergone substantial evolution. The total number of nucleotide and amino acid differences between the LOM vaccine strain and LOM-derived field isolates ranged from 111 and 28 to 148 and 42. These variations were found to be widely distributed throughout the genome and particularly accumulated in non-structural proteins, which might be associated with the potential for LOM to revert to its original low pathogenic form and subsequent horizontal transmission in Jeju swine herds. These data improve our knowledge regarding safety of the LOM vaccine and inherent risk of reversion to natural virulence in host animals.|Chapter 2. Identification and molecular characteristics of classical swine fever virus LOM variants with 3′-UTR INDELs
The classical swine fever virus (CSFV) reemerged in naïve pig herds on Jeju Island, South Korea, due to the accidental introduction of the LOM vaccine strain in 2014. Since this reemergence, the free region has experienced numerous outbreaks, leading to the appearance of endemics in provincial herds. In this study, I investigated the complete genome sequences and the molecular characterization of LOM-derived field CSFV strains with unique insertion-deletion (INDEL) mutations in the 3′-untranslated region (UTR), responsible for ongoing sporadic outbreaks on Jeju Island in 2019. The 2019 emergent Jeju LOM-derived variants had their own INDEL signatures in the 3′-UTR, resulting in changes to the predicted secondary stem-loop structures. The genomes of these strains were 12,297–12,302 nucleotides in length, one-nucleotide (nt) shorter or one-, two-, or four-nt longer than the reference LOM strain. The 3′-UTR INDEL variants shared 98.8–99.0% and 98.3–98.6% identity with the LOM strain at the polyprotein and full-genome levels, respectively. The total number of genetic variations between the LOM vaccine strain and the 3′-UTR INDEL isolates ranged from 161–202 and 37–45 at the nucleotide and amino acid levels, respectively. These mutations were broadly dispersed throughout the genome and particularly clustered in NS2 and 3′-UTR, possibly triggering a reversion to low virulence and allowing the virus to adapt to improve its persistence in the field. This study provides important information about the genetic evolution of the LOM-derived CSFV circulating in the free region, which arises from continuous non-lethal mutations to ensure viral fitness in host animals.|Chapter 3. Pathogenic characteristics of novel classical swine fever virus LOM 3′-UTR INDEL variant
Reemergent local outbreaks of classical swine fever (CSF) occurred simultaneously in multiple pig farms on CSF-free Jeju Island, South Korea, in 2014 because of inadvertent injection of a commercial CSF (LOM) vaccine into pregnant sows. The LOM virus has since spread across the island and has become endemic in Jeju herds, raising concern about possible reversion to virulence of the LOM vaccine. I previously isolated LOM-derived field CSF virus (CSFV) strains with unique insertion-deletion (INDEL) mutations in the 3′-untranslated region (UTR), designated LOM-derived Jeju 3′-UTR INDEL variants, from CSF-recurrent swine farms on Jeju Island in 2019. The present study conducted animal experiments to investigate whether a 2019 emergent LOM 3′-UTR INDEL variant, KNU-1905, has reverted to a pathogenic form in conventional pigs. Experimental animal infection showed that pigs inoculated with the commercial LOM vaccine strain developed no adverse effects compared to the sham-infected pigs. However, KNU-1905 displayed pathogenic characteristics in pigs, including clinical symptoms (e.g., lethargy, conjunctivitis, nasal discharge, and diarrhea), weight loss, and gross lesions. Moreover, viremia, virus shedding in feces and nasal fluids, and viral loads in various tissues of all the KNU-1905-infected pigs were highly significant, in contrast to those of the LOM-infected group in which CSFV RNA was detected only in the serum, nasal, and tonsil samples of one identical pig. In conclusion, the LOM-derived field isolate with molecular variations induced clinical adverse events in pigs, which commonly shed considerable amounts of CSFV. This study provides evidence that the genetic evolution of the LOM-derived CSFV circulating on Jeju Island might have allowed the LOM vaccine to recover its primary prototype and that these variants might have induced chronic or persistent infection in pigs that can shed CSFV in field farms leading to a risk of transmission among pigs or farms in this former CSF-free region.
Author(s)
김주아
Issued Date
2022
Awarded Date
2022-08
Type
Dissertation
URI
https://dcoll.jejunu.ac.kr/common/orgView/000000010672
Alternative Author(s)
Kim, Joo-Ah
Affiliation
제주대학교 대학원
Department
대학원 수의학과
Advisor
손원근
Table Of Contents
Chapter 1 1
1. Abstract 2
2. Introduction 3
3. Materials and Methods 7
4. Results and Discussion 10
References 20
Chapter 2 24
1. Abstract 25
2. Introduction 26
3. Materials and Methods 27
4. Results and Discussion 32
References 45
Chapter 3 48
1. Abstract 49
2. Introduction 51
3. Materials and Methods 54
4. Results 58
5. Discussion 72
References 79
Abstract in Korean 86
Degree
Doctor
Publisher
제주대학교 대학원
Appears in Collections:
General Graduate School > Veterinary Medicine
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  • 엠바고2022-08-18
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