Association of the Host Immune Response with Protection Using a Live Attenuated African Swine Fever Virus Model

AbstractIntroductionAfrican swine fever (ASF) is a pressing economic problem in a number of Eastern European countries. It has also depleted the Chinese sow population by 50%. Managing the disease relies on culling infected pigs or hunting wild boars as sanitary zone creation. The constraints on the development of an efficient vaccine are mainly the virus’ mechanisms of host immune response evasion. The study aimed to adapt a field ASFV strain to established cell lines and to construct recombinant African swine fever virus (ASFV) strain.Material and MethodsThe host immune response modulation genes A238L, EP402R, and 9GL were deleted using the clustered regularly interspaced short palindromic repeats/caspase 9 (CRISPR/Cas9) mutagenesis system. A representative virus isolate (Pol18/28298/Out111) from Poland was isolated in porcine primary pulmonary alveolar macrophage (PPAM) cells. Adaptation of the virus to a few established cell lines was attempted. The plasmids encoding CRISPR/Cas9 genes along with gRNA complementary to the target sequences were designed, synthesised, and transfected into ASFV-infected PPAM cells.ResultsThe reconstituted virus showed similar kinetics of replication in comparison to the parent virus isolate.ConclusionTaking into account the usefulness of the developed CRISPR/Cas9 system it has been shown that modification of the A238L, EP402R, and 9GL genes might occur with low frequency, resulting in difficulties in separation of various virus populations.

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EFFECTS OF MODERATELY VIRULENT AFRICAN SWINE FEVER VIRUS ON INTERLEUKIN-10 PRODUCTION

Veterinary Science Today ◽

10.29326/2304-196x-2019-3-30-23-28 ◽

2019 ◽

pp. 23-28 ◽

Cited By ~ 1

Author(s):

A. S. Pershin ◽

I. V. Shevchenko ◽

A. S. Igolkin ◽

Ye. V. Aronova ◽

N. N. Vlasova

Keyword(s):

Immune Response ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Fever Virus ◽

Noticeable Effect ◽

Specific Antibodies ◽

Virulent Virus ◽

Virus Isolates ◽

Highly Virulent

A characteristic feature of African swine fever virus (ASFV) is the ability to escape from host immune response, affecting macrophages and replicating in them. Besides, ASFV - specific antibodies do not completely neutralize the virus. Cytokines are important factors for various viral infection pathologies. The virulence of ASFV isolates may depend on the capacity to regulate cytokine expression by macrophages. Thus, when comparing in vitro and in vivo cytokine production by macrophages, it was established that infection with low virulent virus isolates leads to an immune response with a predominance of cytokines involved in cellular immunity, such as INF-α and IL-12p40, as compared with infection with highly virulent isolates. The aim of this paper was to study the effect of African swine fever virus on the production of IL-10, a pleiotropic cytokine that inhibits synthesis of cytokines and shows a strong antiinflammatory effect. For this, 12 piglets were experimentally infected intramuscularly with a continuous cell culture-adapted ASFV isolate Vero25 at a dose of 10 HAdU per animal followed by control infection of surviving animals with the reference virus isolate Arm 07 at a dose of 1,000 HAdU per animal. Temperature measurements were taken and blood sampling to obtain serum was conducted during the experiment. IL-10 amount in blood sera was determined using Invitrogen test systems (Thermo Fisher, USA). A higher IL-10 level (15.8–173 pg/ml) was observed in blood sera of dead animals infected with a moderately virulent virus, as compared with surviving pigs (4–5 pg/ml). No correlation between the speed of appearance of specific antibodies and IL-10 serum levels has been established. No noticeable effect of the IL-10 serum level prior to infection on the survival rate of animals has been observed. Further studies are needed to establish a causal relationship, including study of the expression of various cytokines during infection with both low- and highly virulent virus isolates.

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Regulation and Evasion of Host Immune Response by African Swine Fever Virus

Frontiers in Microbiology ◽

10.3389/fmicb.2021.698001 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lei Wu ◽

Bincai Yang ◽

Xu Yuan ◽

Jinxuan Hong ◽

Min Peng ◽

...

Keyword(s):

Immune Response ◽

Latin America ◽

Cellular Immunity ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Host Immune Response ◽

Viral Disease ◽

Dna Virus ◽

Double Stranded Dna ◽

Different Levels

African swine fever (ASF) is an acute lethal hemorrhagic viral disease in domestic pigs and wild boars; is widely epidemic in Africa, Europe, Asia, and Latin America; and poses a huge threat to the pig industry worldwide. ASF is caused by the infection of the ASF virus (ASFV), a cytoplasmic double-stranded DNA virus belonging to the Asfarviridae family. Here, we review how the virus regulates the host immune response and its mechanisms at different levels, including interferon modulation, inflammation, apoptosis, antigen presentation, and cellular immunity.

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AFRICAN SWINE FEVER VIRUS GLYCOPROTEINS p54 AND CD2v IN THE CONTEXT OF IMMUNE RESPONSE MODULATION: BIOINFORMATIC ANALYSIS OF GENETIC VARIABILITY AND HETEROGENEITY

Sel skokhozyaistvennaya Biologiya ◽

10.15389/agrobiology.2015.6.785eng ◽

2015 ◽

Vol 50 (6) ◽

pp. 785-793 ◽

Cited By ~ 1

Author(s):

K.A. Mima ◽

◽

G.S. Burmakina ◽

I.A. Titov ◽

A.S. Malogolovkin ◽

...

Keyword(s):

Immune Response ◽

Genetic Variability ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Bioinformatic Analysis ◽

Fever Virus ◽

Response Modulation ◽

Immune Response Modulation

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In vivo depletion of CD8+ T lymphocytes abrogates protective immunity to African swine fever virus

Journal of General Virology ◽

10.1099/vir.0.81038-0 ◽

2005 ◽

Vol 86 (9) ◽

pp. 2445-2450 ◽

Cited By ~ 87

Author(s):

C. A. L. Oura ◽

M. S. Denyer ◽

H. Takamatsu ◽

R. M. E. Parkhouse

Keyword(s):

Immune Response ◽

T Lymphocytes ◽

Protective Immunity ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Protective Immune Response ◽

Fever Virus ◽

Specific Role ◽

Cd8 T Lymphocytes

To understand the mechanisms involved in protective immunity to African swine fever virus (ASFV) infection, the observation that infection with the avirulent Portuguese ASFV isolate OUR/T88/3 protects outbred pigs from challenge with the virulent Portuguese ASFV isolate OUR/T88/1 was exploited. It was demonstrated that pigs exposed to OUR/T88/3 and then depleted of CD8+ lymphocytes were no longer fully protected from OUR/T88/1 challenge. This indicated that CD8+ lymphocytes play an important role in the protective immune response to ASFV infection and that anti-ASFV antibody alone, from OUR/T88/3 infection, was not sufficient to protect pigs from OUR/T88/1 challenge. Inbred pigs of the cc haplotype infected with OUR/T88/3 were not always protected from OUR/T88/1 challenge and developed both viraemia and fever. Such viraemia was always correlated with increased numbers of circulating CD8β + lymphocytes, indicating a specific role for CD8β + lymphocytes in combating viraemia. These experiments indicate an important role for CD8+ lymphocytes, particularly CD8β + lymphocytes, in ASF protective immunity.

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Structure of African Swine Fever Virus and Associated Molecular Mechanisms Underlying Infection and Immunosuppression: A Review

Frontiers in Immunology ◽

10.3389/fimmu.2021.715582 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yue Wang ◽

Weifang Kang ◽

Wenping Yang ◽

Jing Zhang ◽

Dan Li ◽

...

Keyword(s):

Immune Response ◽

Molecular Mechanism ◽

Molecular Mechanisms ◽

African Swine Fever Virus ◽

Animal Health ◽

African Swine Fever ◽

Fever Virus ◽

Economic Losses ◽

Cell Immune Response ◽

Effective Vaccine

African swine fever (ASF) is an acute, highly contagious, and deadly infectious disease. The mortality rate of the most acute and acute ASF infection is almost 100%. The World Organization for Animal Health [Office International des épizooties (OIE)] lists it as a legally reported animal disease and China lists it as class I animal epidemic. Since the first diagnosed ASF case in China on August 3, 2018, it has caused huge economic losses to animal husbandry. ASF is caused by the African swine fever virus (ASFV), which is the only member of Asfarviridae family. ASFV is and the only insect-borne DNA virus belonging to the Nucleocytoplasmic Large DNA Viruses (NCLDV) family with an icosahedral structure and an envelope. Till date, there are still no effective vaccines or antiviral drugs for the prevention or treatment of ASF. The complex viral genome and its sophisticated ability to regulate the host immune response may be the reason for the difficulty in developing an effective vaccine. This review summarizes the recent findings on ASFV structure, the molecular mechanism of ASFV infection and immunosuppression, and ASFV-encoded proteins to provide comprehensive proteomic information for basic research on ASFV. In addition, it also analyzes the results of previous studies and speculations on the molecular mechanism of ASFV infection, which aids the study of the mechanism of clinical pathological phenomena, and provides a possible direction for an intensive study of ASFV infection mechanism. By summarizing the findings on molecular mechanism of ASFV- regulated host cell immune response, this review provides orientations and ideas for fundamental research on ASFV and provides a theoretical basis for the development of protective vaccines against ASFV.

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The African Swine Fever Virus Proteins p54 and p30 Are Involved in Two Distinct Steps of Virus Attachment and Both Contribute to the Antibody-Mediated Protective Immune Response

Virology ◽

10.1006/viro.1998.9068 ◽

1998 ◽

Vol 243 (2) ◽

pp. 461-471 ◽

Cited By ~ 81

Author(s):

Paulino Gómez-Puertas ◽

Fernando Rodríguez ◽

José M. Oviedo ◽

Alejandro Brun ◽

Covadonga Alonso ◽

...

Keyword(s):

Immune Response ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Protective Immune Response ◽

Fever Virus ◽

Virus Attachment ◽

Virus Proteins

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Systematic analysis of longitudinal serological responses of pigs infected experimentally with African swine fever virus

Journal of General Virology ◽

10.1099/vir.0.82857-0 ◽

2007 ◽

Vol 88 (9) ◽

pp. 2426-2434 ◽

Cited By ~ 25

Author(s):

Ana Luísa Reis ◽

R. M. E. Parkhouse ◽

Ana Raquel Penedos ◽

Carlos Martins ◽

Alexandre Leitão

Keyword(s):

Immune Response ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Viral Proteins ◽

Fever Virus ◽

Antibody Responses ◽

Igg Antibody ◽

Clear Trend ◽

Systematic Analysis ◽

Antibody Titres

The protective immune response to African swine fever virus (ASFV) includes both cellular and serological components. In this study, the role of antibodies in the pathogenicity and diagnosis of African swine fever (ASF) was explored. Accordingly, total and Ig isotype antibody responses against the 12 viral proteins previously demonstrated to be the main targets of serological immunity were evaluated in longitudinally collected sera from pigs infected experimentally with the non-pathogenic ASFV/NH/P68 isolate. Strong total IgG antibody responses were observed against viral proteins E183L/p54, K205R/‘unassigned’, A104R/histone-like and B602L/‘unassigned’; therefore, IgM, IgG1 and IgG2 responses to these proteins were also determined. One protein stimulating IgM (K205R) may have practical potential for the detection of recently infected animals. There was a clear trend towards an IgG1 response to all of the proteins. This may reflect a dominant Th2-controlled immune response. In order to identify possible correlations between these serological responses and the pathogenesis of ASF, total IgG responses to the 12 recombinant proteins were compared in asymptomatic and chronically infected animals. For the proteins NP419L/DNA ligase, CP312R, B646L/p73, K196R/thymidine kinase and K205R, the antibody titres were significantly higher in animals developing lesions. One exception was the antibody response to the A104R/histone-like protein, which was higher in asymptomatic than in chronically infected pigs, suggesting that antibodies against this protein might be an indicator of an effective immune response or that this response is somehow involved in protection.

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Transcriptional immunoresponse of tissue-specific macrophages in swine after infection with African swine fever virus

Bulletin of the Veterinary Institute in Pulawy ◽

10.1515/bvip-2015-0064 ◽

2015 ◽

Vol 59 (4) ◽

pp. 441-446

Author(s):

Andrzej Kowalczyk ◽

Edyta Kozak ◽

Magdalena Łyjak ◽

Zygmunt Pejsak ◽

Krzysztof Niemczuk

Keyword(s):

Immune Response ◽

Immune Responses ◽

Stress Responses ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Fever Virus ◽

Infectious Agents ◽

Blood Monocytes ◽

Immunological Activity ◽

Transcription Factor Activation

Abstract Macrophages and cytokines are important in the control of inflammation and regulation of the immune response. However, they can also contribute to immunopathology in the host after viral infection and the regulatory network can be subverted by infectious agents, including viruses, some of which produce cytokine analogues or have mechanisms that inhibit cytokine function. African swine fever virus (ASFV) encodes a number of proteins which modulate cytokine and chemokine induction, host transcription factor activation, stress responses, and apoptosis. The aim of this review is to elucidate the mechanisms of immune responses to ASFV in different subpopulations of porcine macrophages. A transcriptional immune response in different resident tissue macrophages following ASFV infection was presented in many publications. ASFV-susceptible porcine macrophages can be of several origins, such as peripheral blood, lungs, bone marrow, etc. blood monocytes, blood macrophages, and lung macrophages have demonstrated a modulation of phenotype. Monocyte-derived macrophages could express surface markers not found on their monocyte precursors. Moreover, they can undergo further differentiation after infection and during inflammation. When viruses infect such cells, immunological activity can be seriously impaired or modified.

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