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 »
- Authors:
-
- 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)
- US Dept. of Agriculture (USDA), Greenport, NY (United States). Agricultural Research Service (ARS), Plum Island Animal Disease Center
- 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}
}
Works referenced in this record:
CD2v Interacts with Adaptor Protein AP-1 during African Swine Fever Infection
journal, April 2015
- Pérez-Núñez, Daniel; García-Urdiales, Eduardo; Martínez-Bonet, Marta
- PLOS ONE, Vol. 10, Issue 4
MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms
journal, May 2018
- Kumar, Sudhir; Stecher, Glen; Li, Michael
- Molecular Biology and Evolution, Vol. 35, Issue 6
African Swine Fever Virus Georgia Isolate Harboring Deletions of MGF360 and MGF505 Genes Is Attenuated in Swine and Confers Protection against Challenge with Virulent Parental Virus
journal, March 2015
- O'Donnell, Vivian; Holinka, Lauren G.; Gladue, Douglas P.
- Journal of Virology, Vol. 89, Issue 11
African swine fever virus encodes for an E2-ubiquitin conjugating enzyme that is mono- and di-ubiquitinated and required for viral replication cycle
journal, February 2018
- Freitas, Ferdinando B.; Frouco, Gonçalo; Martins, Carlos
- Scientific Reports, Vol. 8, Issue 1
Viral Miniproteins
journal, September 2014
- DiMaio, Daniel
- Annual Review of Microbiology, Vol. 68, Issue 1
DNA-Binding Properties of African Swine Fever Virus pA104R, a Histone-Like Protein Involved in Viral Replication and Transcription
journal, June 2017
- Frouco, Gonçalo; Freitas, Ferdinando B.; Coelho, João
- Journal of Virology, Vol. 91, Issue 12
Association of the Host Immune Response with Protection Using a Live Attenuated African Swine Fever Virus Model
journal, October 2016
- Carlson, Jolene; O’Donnell, Vivian; Alfano, Marialexia
- Viruses, Vol. 8, Issue 10
The Ep152R ORF of African swine fever virus strain Georgia encodes for an essential gene that interacts with host protein BAG6
journal, September 2016
- Borca, Manuel V.; O’Donnell, Vivian; Holinka, Lauren G.
- Virus Research, Vol. 223
A unique DNA-binding mode of African swine fever virus AP endonuclease
journal, March 2020
- Chen, Yiqing; Chen, Xi; Huang, Qi
- Cell Discovery, Vol. 6, Issue 1
Detecting Individual Sites Subject to Episodic Diversifying Selection
journal, July 2012
- Murrell, Ben; Wertheim, Joel O.; Moola, Sasha
- PLoS Genetics, Vol. 8, Issue 7
Recombinant ASF Live Attenuated Virus Strains as Experimental Vaccine Candidates
journal, April 2022
- Gladue, Douglas P.; Borca, Manuel V.
- Viruses, Vol. 14, Issue 5
A seven-gene-deleted African swine fever virus is safe and effective as a live attenuated vaccine in pigs
journal, March 2020
- Chen, Weiye; Zhao, Dongming; He, Xijun
- Science China Life Sciences, Vol. 63, Issue 5
An African Swine Fever Virus ERV1-ALRHomologue, 9GL, Affects Virion Maturation and Viral Growth in Macrophages and Viral Virulence in Swine
journal, February 2000
- Lewis, T.; Zsak, L.; Burrage, T. G.
- Journal of Virology, Vol. 74, Issue 3
Development of a fluorescent ASFV strain that retains the ability to cause disease in swine
journal, April 2017
- Borca, Manuel V.; O’Donnell, Vivian; Holinka, Lauren G.
- Scientific Reports, Vol. 7, Issue 1
Novel Function of African Swine Fever Virus pE66L in Inhibition of Host Translation by the PKR/eIF2α Pathway
journal, February 2021
- Shen, Zhou; Chen, Chen; Yang, Yilin
- Journal of Virology, Vol. 95, Issue 5
Deletion of CD2-Like (CD2v) and C-Type Lectin-Like (EP153R) Genes from African Swine Fever Virus Georgia-∆9GL Abrogates Its Effectiveness as an Experimental Vaccine
journal, October 2020
- Gladue, Douglas P.; O’Donnell, Vivian; Ramirez-Medina, Elizabeth
- Viruses, Vol. 12, Issue 10
African swine fever virus vaccine candidate ASFV‐G‐
Δ
I177L efficiently protects European and native pig breeds against circulating Vietnamese field strain
journal, October 2021
- Tran, Xuan Hanh; Le, Thi Thu Phuong; Nguyen, Quang Huy
- Transboundary and Emerging Diseases, Vol. 69, Issue 4
Generation and Evaluation of an African Swine Fever Virus Mutant with Deletion of the CD2v and UK Genes
journal, December 2020
- Teklue, Teshale; Wang, Tao; Luo, Yuzi
- Vaccines, Vol. 8, Issue 4
Development of a Highly Effective African Swine Fever Virus Vaccine by Deletion of the I177L Gene Results in Sterile Immunity against the Current Epidemic Eurasia Strain
journal, March 2020
- Borca, Manuel V.; Ramirez-Medina, Elizabeth; Silva, Ediane
- Journal of Virology, Vol. 94, Issue 7
The Progressive Adaptation of a Georgian Isolate of African Swine Fever Virus to Vero Cells Leads to a Gradual Attenuation of Virulence in Swine Corresponding to Major Modifications of the Viral Genome
journal, December 2014
- Krug, Peter W.; Holinka, Lauren G.; O'Donnell, Vivian
- Journal of Virology, Vol. 89, Issue 4
African Swine Fever Virus MGF360-12L Inhibits Type I Interferon Production by Blocking the Interaction of Importin α and NF-κB Signaling Pathway
journal, November 2020
- Zhuo, Yisha; Guo, Zeheng; Ba, Tongtong
- Virologica Sinica, Vol. 36, Issue 2
Deletion of the L7L-L11L Genes Attenuates ASFV and Induces Protection against Homologous Challenge
journal, February 2021
- Zhang, Jingyuan; Zhang, Yanyan; Chen, Teng
- Viruses, Vol. 13, Issue 2
Genome Sequence of African Swine Fever Virus BA71, the Virulent Parental Strain of the Nonpathogenic and Tissue-Culture Adapted BA71V
journal, November 2015
- Rodríguez, Javier M.; Moreno, Leticia Tais; Alejo, Alí
- PLOS ONE, Vol. 10, Issue 11
A Proteomic Atlas of the African Swine Fever Virus Particle
journal, December 2018
- Alejo, Alí; Matamoros, Tania; Guerra, Milagros
- Journal of Virology, Vol. 92, Issue 23
BA71ΔCD2: a New Recombinant Live Attenuated African Swine Fever Virus with Cross-Protective Capabilities
journal, August 2017
- Monteagudo, Paula L.; Lacasta, Anna; López, Elisabeth
- Journal of Virology, Vol. 91, Issue 21
Evaluation of the Safety Profile of the ASFV Vaccine Candidate ASFV-G-ΔI177L
journal, April 2022
- Tran, Xuan Hanh; Phuong, Le Thi Thu; Huy, Nguyen Quang
- Viruses, Vol. 14, Issue 5
Not So Different After All: A Comparison of Methods for Detecting Amino Acid Sites Under Selection
journal, February 2005
- Kosakovsky Pond, Sergei L.; Frost, Simon D. W.
- Molecular Biology and Evolution, Vol. 22, Issue 5
ASFV-G-∆I177L as an Effective Oral Nasal Vaccine against the Eurasia Strain of Africa Swine Fever
journal, April 2021
- Borca, Manuel V.; Ramirez-Medina, Elizabeth; Silva, Ediane
- Viruses, Vol. 13, Issue 5
African Swine Fever Virus MGF-110-9L-deficient Mutant Has Attenuated Virulence in Pigs
journal, March 2021
- Li, Dan; Liu, Yinguang; Qi, Xiaolan
- Virologica Sinica, Vol. 36, Issue 2
African Swine Fever Virus Protein pE199L Mediates Virus Entry by Enabling Membrane Fusion and Core Penetration
journal, August 2020
- Matamoros, Tania; Alejo, Alí; Rodríguez, Javier María
- mBio, Vol. 11, Issue 4
The L83L ORF of African swine fever virus strain Georgia encodes for a non-essential gene that interacts with the host protein IL-1β
journal, April 2018
- Borca, Manuel V.; O’Donnell, Vivian; Holinka, Lauren G.
- Virus Research, Vol. 249
Deletion of the A137R Gene from the Pandemic Strain of African Swine Fever Virus Attenuates the Strain and Offers Protection against the Virulent Pandemic Virus
journal, October 2021
- Gladue, Douglas P.; Ramirez-Medina, Elizabeth; Vuono, Elizabeth
- Journal of Virology, Vol. 95, Issue 21
African Swine Fever Virus Ubiquitin-Conjugating Enzyme Interacts With Host Translation Machinery to Regulate the Host Protein Synthesis
journal, December 2020
- Barrado-Gil, Lucía; Del Puerto, Ana; Muñoz-Moreno, Raquel
- Frontiers in Microbiology, Vol. 11
Deletion of virulence associated genes from attenuated African swine fever virus isolate OUR T88/3 decreases its ability to protect against challenge with virulent virus
journal, August 2013
- Abrams, Charles C.; Goatley, Lynnette; Fishbourne, Emma
- Virology, Vol. 443, Issue 1
The MGF360-16R ORF of African Swine Fever Virus Strain Georgia Encodes for a Nonessential Gene That Interacts with Host Proteins SERTAD3 and SDCBP
journal, January 2020
- Ramírez-Medina, Elizabeth; Vuono, Elizabeth A.; Velazquez-Salinas, Lauro
- Viruses, Vol. 12, Issue 1
Deletion of a CD2-Like Gene, 8-DR, from African Swine Fever Virus Affects Viral Infection in Domestic Swine
journal, April 1998
- Borca, M. V.; Carrillo, C.; Zsak, L.
- Journal of Virology, Vol. 72, Issue 4
Simultaneous Deletion of the 9GL and UK Genes from the African Swine Fever Virus Georgia 2007 Isolate Offers Increased Safety and Protection against Homologous Challenge
journal, January 2017
- O'Donnell, Vivian; Risatti, Guillermo R.; Holinka, Lauren G.
- Journal of Virology, Vol. 91, Issue 1
African Swine Fever Virus MGF-505-7R Negatively Regulates cGAS–STING-Mediated Signaling Pathway
journal, March 2021
- Li, Dan; Yang, Wenping; Li, Lulu
- The Journal of Immunology, Vol. 206, Issue 8
CRISPR/Cas Gene Editing of a Large DNA Virus: African Swine Fever Virus
journal, January 2018
- Borca, Manuel; Berggren, Keith; Ramirez-Medina, Elizabeth
- BIO-PROTOCOL, Vol. 8, Issue 16
Genomic Analysis of Highly Virulent Georgia 2007/1 Isolate of African Swine Fever Virus
journal, April 2011
- Chapman, David A. G.; Darby, Alistair C.; Da Silva, Melissa
- Emerging Infectious Diseases, Vol. 17, Issue 4
Attenuated and non‐haemadsorbing (non‐ HAD ) genotype II African swine fever virus ( ASFV ) isolated in Europe, Latvia 2017
journal, February 2019
- Gallardo, Carmina; Soler, Alejandro; Rodze, Ieva
- Transboundary and Emerging Diseases, Vol. 66, Issue 3
CRISPR-Cas9, a tool to efficiently increase the development of recombinant African swine fever viruses
journal, February 2018
- Borca, Manuel V.; Holinka, Lauren G.; Berggren, Keith A.
- Scientific Reports, Vol. 8, Issue 1
African Swine Fever Virus Georgia 2007 with a Deletion of Virulence-Associated Gene 9GL (B119L), when Administered at Low Doses, Leads to Virus Attenuation in Swine and Induces an Effective Protection against Homologous Challenge
journal, June 2015
- O'Donnell, Vivian; Holinka, Lauren G.; Krug, Peter W.
- Journal of Virology, Vol. 89, Issue 16
GARD: a genetic algorithm for recombination detection
journal, November 2006
- Kosakovsky Pond, S. L.; Posada, D.; Gravenor, M. B.
- Bioinformatics, Vol. 22, Issue 24
Differential Effect of the Deletion of African Swine Fever Virus Virulence-Associated Genes in the Induction of Attenuation of the Highly Virulent Georgia Strain
journal, July 2019
- Ramirez-Medina, Elizabeth; Vuono, Elizabeth; O’Donnell, Vivian
- Viruses, Vol. 11, Issue 7
African swine fever virus Georgia isolate harboring deletions of 9GL and MGF360/505 genes is highly attenuated in swine but does not confer protection against parental virus challenge
journal, August 2016
- O’Donnell, Vivian; Holinka, Lauren G.; Sanford, Brenton
- Virus Research, Vol. 221
A Simple Method of Estimating Fifty per cent Endpoints12
journal, May 1938
- Reed, L. J.; Muench, H.
- American Journal of Epidemiology, Vol. 27, Issue 3
Pfam: The protein families database in 2021
journal, October 2020
- Mistry, Jaina; Chuguransky, Sara; Williams, Lowri
- Nucleic Acids Research, Vol. 49, Issue D1