Cargando…
The baseline immunological and hygienic status of pigs impact disease severity of African swine fever
African Swine Fever virus (ASFV) is a large double-enveloped DNA virus of the Asfarviridae family that causes a lethal hemorrhagic disease in domestic pigs and wild boars. Since 2007, a highly virulent genotype II strain has emerged and spread in Europe and South-East Asia, where millions of animals...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409533/ https://www.ncbi.nlm.nih.gov/pubmed/36006954 http://dx.doi.org/10.1371/journal.ppat.1010522 |
_version_ | 1784774874399506432 |
---|---|
author | Radulovic, Emilia Mehinagic, Kemal Wüthrich, Tsering Hilty, Markus Posthaus, Horst Summerfield, Artur Ruggli, Nicolas Benarafa, Charaf |
author_facet | Radulovic, Emilia Mehinagic, Kemal Wüthrich, Tsering Hilty, Markus Posthaus, Horst Summerfield, Artur Ruggli, Nicolas Benarafa, Charaf |
author_sort | Radulovic, Emilia |
collection | PubMed |
description | African Swine Fever virus (ASFV) is a large double-enveloped DNA virus of the Asfarviridae family that causes a lethal hemorrhagic disease in domestic pigs and wild boars. Since 2007, a highly virulent genotype II strain has emerged and spread in Europe and South-East Asia, where millions of animals succumbed to the disease. Field- and laboratory-attenuated strains of ASFV cause highly variable clinical disease severity and survival, and mechanisms remain unclear. We hypothesized that the immunological and hygienic status of pigs is a determinant of ASF disease course. Here we compared the immunological profile at baseline and in response to ASFV infection in specific pathogen-free (SPF) and farm-raised Large White domestic pigs. At steady state, SPF pigs showed lower white blood cell counts and a lower basal inflammatory and antiviral transcriptomic profile compared to farm pigs, associated with profound differences in gut microbiome composition. After inoculation with a highly virulent ASFV genotype II strain (Armenia 2008), severe clinical signs, viremia and pro-inflammatory cytokines appeared sooner in SPF pigs, indicating a reduced capacity to control early virus replication. In contrast, during infection with an attenuated field isolate (Estonia 2014), SPF pigs presented a milder and shorter clinical disease with full recovery, whereas farm pigs presented severe protracted disease with 50% lethality. Interestingly, farm pigs showed higher production of inflammatory cytokines, whereas SPF pigs produced more anti-inflammatory IL-1ra early after infection and presented a stronger expansion of leukocytes in the recovery phase. Altogether, our data indicate that the hygiene-dependent innate immune status has a double-edge sword impact on immune responses in ASF pathogenesis. While the higher baseline innate immune activity helps the host in reducing initial virus replication, it promotes immunopathological cytokine responses, and delays lymphocyte proliferation after infection with an attenuated strain. Such effects should be considered for live vaccine development and vigilance. |
format | Online Article Text |
id | pubmed-9409533 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-94095332022-08-26 The baseline immunological and hygienic status of pigs impact disease severity of African swine fever Radulovic, Emilia Mehinagic, Kemal Wüthrich, Tsering Hilty, Markus Posthaus, Horst Summerfield, Artur Ruggli, Nicolas Benarafa, Charaf PLoS Pathog Research Article African Swine Fever virus (ASFV) is a large double-enveloped DNA virus of the Asfarviridae family that causes a lethal hemorrhagic disease in domestic pigs and wild boars. Since 2007, a highly virulent genotype II strain has emerged and spread in Europe and South-East Asia, where millions of animals succumbed to the disease. Field- and laboratory-attenuated strains of ASFV cause highly variable clinical disease severity and survival, and mechanisms remain unclear. We hypothesized that the immunological and hygienic status of pigs is a determinant of ASF disease course. Here we compared the immunological profile at baseline and in response to ASFV infection in specific pathogen-free (SPF) and farm-raised Large White domestic pigs. At steady state, SPF pigs showed lower white blood cell counts and a lower basal inflammatory and antiviral transcriptomic profile compared to farm pigs, associated with profound differences in gut microbiome composition. After inoculation with a highly virulent ASFV genotype II strain (Armenia 2008), severe clinical signs, viremia and pro-inflammatory cytokines appeared sooner in SPF pigs, indicating a reduced capacity to control early virus replication. In contrast, during infection with an attenuated field isolate (Estonia 2014), SPF pigs presented a milder and shorter clinical disease with full recovery, whereas farm pigs presented severe protracted disease with 50% lethality. Interestingly, farm pigs showed higher production of inflammatory cytokines, whereas SPF pigs produced more anti-inflammatory IL-1ra early after infection and presented a stronger expansion of leukocytes in the recovery phase. Altogether, our data indicate that the hygiene-dependent innate immune status has a double-edge sword impact on immune responses in ASF pathogenesis. While the higher baseline innate immune activity helps the host in reducing initial virus replication, it promotes immunopathological cytokine responses, and delays lymphocyte proliferation after infection with an attenuated strain. Such effects should be considered for live vaccine development and vigilance. Public Library of Science 2022-08-25 /pmc/articles/PMC9409533/ /pubmed/36006954 http://dx.doi.org/10.1371/journal.ppat.1010522 Text en © 2022 Radulovic et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Radulovic, Emilia Mehinagic, Kemal Wüthrich, Tsering Hilty, Markus Posthaus, Horst Summerfield, Artur Ruggli, Nicolas Benarafa, Charaf The baseline immunological and hygienic status of pigs impact disease severity of African swine fever |
title | The baseline immunological and hygienic status of pigs impact disease severity of African swine fever |
title_full | The baseline immunological and hygienic status of pigs impact disease severity of African swine fever |
title_fullStr | The baseline immunological and hygienic status of pigs impact disease severity of African swine fever |
title_full_unstemmed | The baseline immunological and hygienic status of pigs impact disease severity of African swine fever |
title_short | The baseline immunological and hygienic status of pigs impact disease severity of African swine fever |
title_sort | baseline immunological and hygienic status of pigs impact disease severity of african swine fever |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409533/ https://www.ncbi.nlm.nih.gov/pubmed/36006954 http://dx.doi.org/10.1371/journal.ppat.1010522 |
work_keys_str_mv | AT radulovicemilia thebaselineimmunologicalandhygienicstatusofpigsimpactdiseaseseverityofafricanswinefever AT mehinagickemal thebaselineimmunologicalandhygienicstatusofpigsimpactdiseaseseverityofafricanswinefever AT wuthrichtsering thebaselineimmunologicalandhygienicstatusofpigsimpactdiseaseseverityofafricanswinefever AT hiltymarkus thebaselineimmunologicalandhygienicstatusofpigsimpactdiseaseseverityofafricanswinefever AT posthaushorst thebaselineimmunologicalandhygienicstatusofpigsimpactdiseaseseverityofafricanswinefever AT summerfieldartur thebaselineimmunologicalandhygienicstatusofpigsimpactdiseaseseverityofafricanswinefever AT rugglinicolas thebaselineimmunologicalandhygienicstatusofpigsimpactdiseaseseverityofafricanswinefever AT benarafacharaf thebaselineimmunologicalandhygienicstatusofpigsimpactdiseaseseverityofafricanswinefever AT radulovicemilia baselineimmunologicalandhygienicstatusofpigsimpactdiseaseseverityofafricanswinefever AT mehinagickemal baselineimmunologicalandhygienicstatusofpigsimpactdiseaseseverityofafricanswinefever AT wuthrichtsering baselineimmunologicalandhygienicstatusofpigsimpactdiseaseseverityofafricanswinefever AT hiltymarkus baselineimmunologicalandhygienicstatusofpigsimpactdiseaseseverityofafricanswinefever AT posthaushorst baselineimmunologicalandhygienicstatusofpigsimpactdiseaseseverityofafricanswinefever AT summerfieldartur baselineimmunologicalandhygienicstatusofpigsimpactdiseaseseverityofafricanswinefever AT rugglinicolas baselineimmunologicalandhygienicstatusofpigsimpactdiseaseseverityofafricanswinefever AT benarafacharaf baselineimmunologicalandhygienicstatusofpigsimpactdiseaseseverityofafricanswinefever |