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Title: Deletion of the H108R Gene Reduces Virulence of the Pandemic Eurasia Strain of African Swine Fever Virus with Surviving Animals Being Protected against Virulent Challenge

Abstract

African swine fever virus (ASFV) is the etiological agent of African swine fever (ASF), a devastating disease affecting domestic and wild swine and currently causing a global pandemic, severely affecting swine production. Here, we demonstrate that the deletion of the previously uncharacterized ASFV gene, H108R from the highly virulent ASFV-Georgia2007 (ASFV-G) genome strain, reduces virulence in domestic swine. ASFV-G-DH108R, a recombinant virus with the H108R gene deleted, was used to evaluate the involvement of the H108R gene for ASFV replication and virulence in swine. ASFV-G-DH108R showed a delayed replication in swine macrophage cultures. A group of five pigs, intramuscularly inoculated with 102 HAD50 of ASFV-G-DH108R, was observed over a 28-day period and compared with a similar group of animals inoculated with similar doses of the parental virulent virus. While all animals inoculated with ASFV-G developed an acute fatal disease, ASFV-G-DH108R inoculated animals, with the exception of one animal showing a protracted but fatal form of the disease, all survived the infection, remaining clinically healthy during the observational period. The surviving animals presented protracted viremias with lower virus titers compared with those of animals inoculated with the parental virus, and all of them developed a strong virus-specific antibody response. Importantly, allmore » animals surviving ASFV-G-DAH108R infection were protected when challenged with the virulent parental strain, ASFV-G. This report constitutes the first evidence that the H108R gene is involved in ASFV virulence in swine and that the deletion of this gene may be used as a tool to increase the attenuation of currently experimental vaccines to improve their safety profiles.« less

Authors:
 [1];  [2];  [2];  [3];  [2];  [2];  [3];  [2]; ORCiD logo [2];  [2]
  1. US Dept. of Agriculture (USDA), Greenport, NY (United States). Agricultural Research Service (ARS), Plum Island Animal Disease Center; Univ. of Wisconsin, Madison, WI (United States)
  2. US Dept. of Agriculture (USDA), Greenport, NY (United States). Agricultural Research Service (ARS), Plum Island Animal Disease Center
  3. US Dept. of Agriculture (USDA), Greenport, NY (United States). Agricultural Research Service (ARS), Plum Island Animal Disease Center; Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
Publication Date:
Research Org.:
Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Office of Science (SC); USDA
OSTI Identifier:
1982972
Grant/Contract Number:  
SC0014664
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Virology
Additional Journal Information:
Journal Volume: 96; Journal Issue: 14; Journal ID: ISSN 0022-538X
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Virology; ASF; ASFV; African Swine fever; H108R; pandemic; virulence

Citation Formats

Vuono, Elizabeth, Ramirez-Medina, Elizabeth, Silva, Ediane, Rai, Ayushi, Pruitt, Sarah, Espinoza, Nallely, Valladares, Alyssa, Velazquez-Salinas, Lauro, Gladue, Douglas P., and Borca, Manuel V. Deletion of the H108R Gene Reduces Virulence of the Pandemic Eurasia Strain of African Swine Fever Virus with Surviving Animals Being Protected against Virulent Challenge. United States: N. p., 2022. Web. doi:10.1128/jvi.00545-22.
Vuono, Elizabeth, Ramirez-Medina, Elizabeth, Silva, Ediane, Rai, Ayushi, Pruitt, Sarah, Espinoza, Nallely, Valladares, Alyssa, Velazquez-Salinas, Lauro, Gladue, Douglas P., & Borca, Manuel V. Deletion of the H108R Gene Reduces Virulence of the Pandemic Eurasia Strain of African Swine Fever Virus with Surviving Animals Being Protected against Virulent Challenge. United States. https://doi.org/10.1128/jvi.00545-22
Vuono, Elizabeth, Ramirez-Medina, Elizabeth, Silva, Ediane, Rai, Ayushi, Pruitt, Sarah, Espinoza, Nallely, Valladares, Alyssa, Velazquez-Salinas, Lauro, Gladue, Douglas P., and Borca, Manuel V. Wed . "Deletion of the H108R Gene Reduces Virulence of the Pandemic Eurasia Strain of African Swine Fever Virus with Surviving Animals Being Protected against Virulent Challenge". United States. https://doi.org/10.1128/jvi.00545-22. https://www.osti.gov/servlets/purl/1982972.
@article{osti_1982972,
title = {Deletion of the H108R Gene Reduces Virulence of the Pandemic Eurasia Strain of African Swine Fever Virus with Surviving Animals Being Protected against Virulent Challenge},
author = {Vuono, Elizabeth and Ramirez-Medina, Elizabeth and Silva, Ediane and Rai, Ayushi and Pruitt, Sarah and Espinoza, Nallely and Valladares, Alyssa and Velazquez-Salinas, Lauro and Gladue, Douglas P. and Borca, Manuel V.},
abstractNote = {African swine fever virus (ASFV) is the etiological agent of African swine fever (ASF), a devastating disease affecting domestic and wild swine and currently causing a global pandemic, severely affecting swine production. Here, we demonstrate that the deletion of the previously uncharacterized ASFV gene, H108R from the highly virulent ASFV-Georgia2007 (ASFV-G) genome strain, reduces virulence in domestic swine. ASFV-G-DH108R, a recombinant virus with the H108R gene deleted, was used to evaluate the involvement of the H108R gene for ASFV replication and virulence in swine. ASFV-G-DH108R showed a delayed replication in swine macrophage cultures. A group of five pigs, intramuscularly inoculated with 102 HAD50 of ASFV-G-DH108R, was observed over a 28-day period and compared with a similar group of animals inoculated with similar doses of the parental virulent virus. While all animals inoculated with ASFV-G developed an acute fatal disease, ASFV-G-DH108R inoculated animals, with the exception of one animal showing a protracted but fatal form of the disease, all survived the infection, remaining clinically healthy during the observational period. The surviving animals presented protracted viremias with lower virus titers compared with those of animals inoculated with the parental virus, and all of them developed a strong virus-specific antibody response. Importantly, all animals surviving ASFV-G-DAH108R infection were protected when challenged with the virulent parental strain, ASFV-G. This report constitutes the first evidence that the H108R gene is involved in ASFV virulence in swine and that the deletion of this gene may be used as a tool to increase the attenuation of currently experimental vaccines to improve their safety profiles.},
doi = {10.1128/jvi.00545-22},
journal = {Journal of Virology},
number = 14,
volume = 96,
place = {United States},
year = {Wed Jul 27 00:00:00 EDT 2022},
month = {Wed Jul 27 00:00:00 EDT 2022}
}

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