Immunopathological features of highly pathogenic Korean Lineage B PRRSV-2: insights into virulence indicators and host immune responses

IntroductionPorcine reproductive and respiratory syndrome virus (PRRSV) remains one of the most economically devastating pathogens in swine, primarily due to its extensive genetic diversity and lineage-dependent pathogenicity. Despite widespread vaccination, distinct PRRSV-2 lineages continue to cir...

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Main Authors: Gyeong-Seo Park, Seung-Chai Kim, Hwan-Ju Kim, Chang-Gi Jeong, Sang-Chul Kang, Go-Eun Shin, Seoung-Hee Kim, Hye-Young Jeong, Kyoung-Ki Lee, Sang-Myeong Lee, Won-Il Kim
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Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1599468/full
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author Gyeong-Seo Park
Gyeong-Seo Park
Seung-Chai Kim
Hwan-Ju Kim
Chang-Gi Jeong
Chang-Gi Jeong
Sang-Chul Kang
Go-Eun Shin
Seoung-Hee Kim
Hye-Young Jeong
Kyoung-Ki Lee
Sang-Myeong Lee
Won-Il Kim
author_facet Gyeong-Seo Park
Gyeong-Seo Park
Seung-Chai Kim
Hwan-Ju Kim
Chang-Gi Jeong
Chang-Gi Jeong
Sang-Chul Kang
Go-Eun Shin
Seoung-Hee Kim
Hye-Young Jeong
Kyoung-Ki Lee
Sang-Myeong Lee
Won-Il Kim
author_sort Gyeong-Seo Park
collection DOAJ
description IntroductionPorcine reproductive and respiratory syndrome virus (PRRSV) remains one of the most economically devastating pathogens in swine, primarily due to its extensive genetic diversity and lineage-dependent pathogenicity. Despite widespread vaccination, distinct PRRSV-2 lineages continue to circulate in Korea. This study aimed to elucidate the immunopathological features of two Korean-specific Lineage B (LKB) strains, GGYC45 and PJ10, compared with a vaccine-like L5 strain, M8.MethodsThirty, 4-week-old piglets were divided into M8-, GGYC45-, PJ10-infected groups, and control. After acclimatization, pigs were intramuscularly inoculated with PRRSV-2 strains. Pigs were monitored, and blood and nasal swabs were collected. At 12- and 28 days post-infection (dpi), pigs were euthanized for histopathological analysis and tissue collection. Histopathological evaluations were conducted on lung and brain tissues. Bronchoalveolar lavage (BAL) cells and lung tissues were analyzed for immune responses, including flow cytometry (FACS), cytokine expression, viral load, and expression of immune checkpoint molecules.ResultsBoth LKB strains (GGYC45 and PJ10) observed moderate to severe clinical symptoms. Notably, PJ10-infected pigs exhibited high mortality accompanied by significantly (p < 0.05) low average daily weight gain (ADWG), high temperatures, and high levels of viremia and viral loads in various tissues. Immunopathological analysis showed severe respiratory and neurological lesions in PJ10-infected pigs. PJ10 destroyed over 90% of residential alveolar macrophages and increased infiltrated monocyte-derived cells and T lymphocytes in the lungs up to 12 dpi. Pigs infected with the GGYC45 strain exhibited a relatively lower virulence profile than those infected with the PJ10 strain; however, GGYC45 induced moderate pathogenicity in pigs. Regardless of the lineages or genotypes, pigs infected with PRRSV-2 increased immune checkpoint molecule expression, such as PD1, PDL1, CTLA4, IDO1, and LAG3 in BAL cells, resulting in insufficient T cell activation.ConclusionThese results highlight the differential virulence and immunomodulatory profiles of genetically distinct PRRSV-2 strains circulating in Korea. The heightened immune checkpoint expression, particularly in PJ10-infected pigs, underscores a potential mechanism of PRRSV-induced immune suppression and viral persistence. This study provides critical insights into PRRSV pathogenesis and host-virus interactions and supports the need for lineage-adapted control strategies that account for both the genetic heterogeneity of PRRSV and immune evasion mechanisms.
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spelling doaj-art-ad52f8cf2b22430fb8067d70830e981c2025-08-20T03:21:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.15994681599468Immunopathological features of highly pathogenic Korean Lineage B PRRSV-2: insights into virulence indicators and host immune responsesGyeong-Seo Park0Gyeong-Seo Park1Seung-Chai Kim2Hwan-Ju Kim3Chang-Gi Jeong4Chang-Gi Jeong5Sang-Chul Kang6Go-Eun Shin7Seoung-Hee Kim8Hye-Young Jeong9Kyoung-Ki Lee10Sang-Myeong Lee11Won-Il Kim12Collenge of Veterinary Medicine, Jeonbuk National University, Iksan, Republic of KoreaVaccine Lab, WOOGENE B&G Co., LTD., Seoul, Republic of KoreaCollenge of Veterinary Medicine, Jeonbuk National University, Iksan, Republic of KoreaCollenge of Veterinary Medicine, Jeonbuk National University, Iksan, Republic of KoreaCollenge of Veterinary Medicine, Jeonbuk National University, Iksan, Republic of KoreaBiosafety Research Institute, Jeonbuk National University, Iksan, Republic of KoreaAnimal Clinical Evaluation Center, Optipharm Inc, Cheongju, Republic of KoreaAnimal Disease Diagnostic Division, Animal and Plant Quarantine Agency, Gimcheon, Republic of KoreaAnimal Disease Diagnostic Division, Animal and Plant Quarantine Agency, Gimcheon, Republic of KoreaAnimal Disease Diagnostic Division, Animal and Plant Quarantine Agency, Gimcheon, Republic of KoreaAnimal Disease Diagnostic Division, Animal and Plant Quarantine Agency, Gimcheon, Republic of KoreaCollege of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of KoreaCollenge of Veterinary Medicine, Jeonbuk National University, Iksan, Republic of KoreaIntroductionPorcine reproductive and respiratory syndrome virus (PRRSV) remains one of the most economically devastating pathogens in swine, primarily due to its extensive genetic diversity and lineage-dependent pathogenicity. Despite widespread vaccination, distinct PRRSV-2 lineages continue to circulate in Korea. This study aimed to elucidate the immunopathological features of two Korean-specific Lineage B (LKB) strains, GGYC45 and PJ10, compared with a vaccine-like L5 strain, M8.MethodsThirty, 4-week-old piglets were divided into M8-, GGYC45-, PJ10-infected groups, and control. After acclimatization, pigs were intramuscularly inoculated with PRRSV-2 strains. Pigs were monitored, and blood and nasal swabs were collected. At 12- and 28 days post-infection (dpi), pigs were euthanized for histopathological analysis and tissue collection. Histopathological evaluations were conducted on lung and brain tissues. Bronchoalveolar lavage (BAL) cells and lung tissues were analyzed for immune responses, including flow cytometry (FACS), cytokine expression, viral load, and expression of immune checkpoint molecules.ResultsBoth LKB strains (GGYC45 and PJ10) observed moderate to severe clinical symptoms. Notably, PJ10-infected pigs exhibited high mortality accompanied by significantly (p < 0.05) low average daily weight gain (ADWG), high temperatures, and high levels of viremia and viral loads in various tissues. Immunopathological analysis showed severe respiratory and neurological lesions in PJ10-infected pigs. PJ10 destroyed over 90% of residential alveolar macrophages and increased infiltrated monocyte-derived cells and T lymphocytes in the lungs up to 12 dpi. Pigs infected with the GGYC45 strain exhibited a relatively lower virulence profile than those infected with the PJ10 strain; however, GGYC45 induced moderate pathogenicity in pigs. Regardless of the lineages or genotypes, pigs infected with PRRSV-2 increased immune checkpoint molecule expression, such as PD1, PDL1, CTLA4, IDO1, and LAG3 in BAL cells, resulting in insufficient T cell activation.ConclusionThese results highlight the differential virulence and immunomodulatory profiles of genetically distinct PRRSV-2 strains circulating in Korea. The heightened immune checkpoint expression, particularly in PJ10-infected pigs, underscores a potential mechanism of PRRSV-induced immune suppression and viral persistence. This study provides critical insights into PRRSV pathogenesis and host-virus interactions and supports the need for lineage-adapted control strategies that account for both the genetic heterogeneity of PRRSV and immune evasion mechanisms.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1599468/fullporcine reproductive and respiratory syndrome virusKorean Lineagepathogenicityimmune characteristicshost immunityimmune checkpoint molecules
spellingShingle Gyeong-Seo Park
Gyeong-Seo Park
Seung-Chai Kim
Hwan-Ju Kim
Chang-Gi Jeong
Chang-Gi Jeong
Sang-Chul Kang
Go-Eun Shin
Seoung-Hee Kim
Hye-Young Jeong
Kyoung-Ki Lee
Sang-Myeong Lee
Won-Il Kim
Immunopathological features of highly pathogenic Korean Lineage B PRRSV-2: insights into virulence indicators and host immune responses
Frontiers in Immunology
porcine reproductive and respiratory syndrome virus
Korean Lineage
pathogenicity
immune characteristics
host immunity
immune checkpoint molecules
title Immunopathological features of highly pathogenic Korean Lineage B PRRSV-2: insights into virulence indicators and host immune responses
title_full Immunopathological features of highly pathogenic Korean Lineage B PRRSV-2: insights into virulence indicators and host immune responses
title_fullStr Immunopathological features of highly pathogenic Korean Lineage B PRRSV-2: insights into virulence indicators and host immune responses
title_full_unstemmed Immunopathological features of highly pathogenic Korean Lineage B PRRSV-2: insights into virulence indicators and host immune responses
title_short Immunopathological features of highly pathogenic Korean Lineage B PRRSV-2: insights into virulence indicators and host immune responses
title_sort immunopathological features of highly pathogenic korean lineage b prrsv 2 insights into virulence indicators and host immune responses
topic porcine reproductive and respiratory syndrome virus
Korean Lineage
pathogenicity
immune characteristics
host immunity
immune checkpoint molecules
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1599468/full
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