Deletion of the Gene for the Type I Interferon Inhibitor I329L from the Attenuated African Swine Fever Virus OURT88/3 Strain Reduces Protection Induced in Pigs

Live attenuated vaccines are considered to be the fastest route to the development of a safe and efficacious African swine fever (ASF) vaccine. Infection with the naturally attenuated OURT88/3 strain induces protection against challenge with virulent isolates from the same or closely related genotyp...

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Authors: Reis, Ana Luisa; Goatley, Lynnette C.; Jabbar, Tamara; López Fernandez, Elisabet|||0000-0003-4253-330X; Rathakrishnan, Anusyah; Dixon, Linda|||0000-0003-3845-3016
Format: Article
Publication date:2020
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:252639
Online Access:https://ddd.uab.cat/record/252639
https://dx.doi.org/urn:doi:10.3390/vaccines8020262
Access Level:Open access
Keyword:African swine fever virus
Interferon
I329L
Vaccine
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author Reis, Ana Luisa
author2 Goatley, Lynnette C.
Jabbar, Tamara
López Fernandez, Elisabet|||0000-0003-4253-330X
Rathakrishnan, Anusyah
Dixon, Linda|||0000-0003-3845-3016
author2_role author
author
author
author
author
author_browse Dixon, Linda|||0000-0003-3845-3016
Goatley, Lynnette C.
Jabbar, Tamara
López Fernandez, Elisabet|||0000-0003-4253-330X
Rathakrishnan, Anusyah
Reis, Ana Luisa
author_facet Reis, Ana Luisa
Goatley, Lynnette C.
Jabbar, Tamara
López Fernandez, Elisabet|||0000-0003-4253-330X
Rathakrishnan, Anusyah
Dixon, Linda|||0000-0003-3845-3016
author_role author
collection Dipòsit Digital de Documents de la UAB
description Live attenuated vaccines are considered to be the fastest route to the development of a safe and efficacious African swine fever (ASF) vaccine. Infection with the naturally attenuated OURT88/3 strain induces protection against challenge with virulent isolates from the same or closely related genotypes. However, adverse clinical signs following immunisation have been observed. Here, we attempted to increase the OURT88/3 safety profile by deleting I329L, a gene previously shown to inhibit the host innate immune response. The resulting virus, OURT88/3ΔI329L, was tested in vitro to evaluate the replication and expression of type I interferon (IFN) and in vivo by immunisation and lethal challenge experiments in pigs. No differences were observed regarding replication; however, increased amounts of both IFN-β and IFN- α were observed in macrophages infected with the deletion mutant virus. Unexpectedly, the deletion of I329L markedly reduced protection against challenge with the virulent OURT88/1 isolate. This was associated with a decrease in both antibody levels against VP72 and the number of IFN-γ-producing cells in the blood of non-protected animals. Furthermore, a significant increase in IL-10 levels in serum was observed in pigs immunised with OURT88/3ΔI329L following challenge. Interestingly, the deletion of the I329L gene failed to attenuate the virulent Georgia/2007 isolate.
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instname_str Universitat Autònoma de Barcelona
language eng
network_acronym_str ES
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oai_identifier_str oai:ddd.uab.cat:252639
publishDate 2020
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spelling Deletion of the Gene for the Type I Interferon Inhibitor I329L from the Attenuated African Swine Fever Virus OURT88/3 Strain Reduces Protection Induced in Pigs Reis, Ana Luisa Goatley, Lynnette C. Jabbar, Tamara López Fernandez, Elisabet|||0000-0003-4253-330X Rathakrishnan, Anusyah Dixon, Linda|||0000-0003-3845-3016 African swine fever virus Interferon I329L Vaccine Live attenuated vaccines are considered to be the fastest route to the development of a safe and efficacious African swine fever (ASF) vaccine. Infection with the naturally attenuated OURT88/3 strain induces protection against challenge with virulent isolates from the same or closely related genotypes. However, adverse clinical signs following immunisation have been observed. Here, we attempted to increase the OURT88/3 safety profile by deleting I329L, a gene previously shown to inhibit the host innate immune response. The resulting virus, OURT88/3ΔI329L, was tested in vitro to evaluate the replication and expression of type I interferon (IFN) and in vivo by immunisation and lethal challenge experiments in pigs. No differences were observed regarding replication; however, increased amounts of both IFN-β and IFN- α were observed in macrophages infected with the deletion mutant virus. Unexpectedly, the deletion of I329L markedly reduced protection against challenge with the virulent OURT88/1 isolate. This was associated with a decrease in both antibody levels against VP72 and the number of IFN-γ-producing cells in the blood of non-protected animals. Furthermore, a significant increase in IL-10 levels in serum was observed in pigs immunised with OURT88/3ΔI329L following challenge. Interestingly, the deletion of the I329L gene failed to attenuate the virulent Georgia/2007 isolate. https://ddd.uab.cat/record/252639 https://dx.doi.org/urn:doi:10.3390/vaccines8020262
spellingShingle Deletion of the Gene for the Type I Interferon Inhibitor I329L from the Attenuated African Swine Fever Virus OURT88/3 Strain Reduces Protection Induced in Pigs
Reis, Ana Luisa
African swine fever virus
Interferon
I329L
Vaccine
title Deletion of the Gene for the Type I Interferon Inhibitor I329L from the Attenuated African Swine Fever Virus OURT88/3 Strain Reduces Protection Induced in Pigs
title_full Deletion of the Gene for the Type I Interferon Inhibitor I329L from the Attenuated African Swine Fever Virus OURT88/3 Strain Reduces Protection Induced in Pigs
title_fullStr Deletion of the Gene for the Type I Interferon Inhibitor I329L from the Attenuated African Swine Fever Virus OURT88/3 Strain Reduces Protection Induced in Pigs
title_full_unstemmed Deletion of the Gene for the Type I Interferon Inhibitor I329L from the Attenuated African Swine Fever Virus OURT88/3 Strain Reduces Protection Induced in Pigs
title_short Deletion of the Gene for the Type I Interferon Inhibitor I329L from the Attenuated African Swine Fever Virus OURT88/3 Strain Reduces Protection Induced in Pigs
title_sort Deletion of the Gene for the Type I Interferon Inhibitor I329L from the Attenuated African Swine Fever Virus OURT88/3 Strain Reduces Protection Induced in Pigs
topic African swine fever virus
Interferon
I329L
Vaccine
topic_facet African swine fever virus
Interferon
I329L
Vaccine
url https://ddd.uab.cat/record/252639
https://dx.doi.org/urn:doi:10.3390/vaccines8020262