veterinaryВетеринария сегодняVeterinary Science Today2304-196X2658-6959"Veinard"10.29326/2304-196X-2019-3-30-23-28veterinary-424Research ArticleБОЛЕЗНИ СВИНЕЙPORCINE DISEASESВЛИЯНИЕ УМЕРЕННО ВИРУЛЕНТНОГО ВИРУСА АЧС НА ПРОДУКЦИЮ ИНТЕРЛЕЙКИНА-10EFFECTS OF MODERATELY VIRULENT AFRICAN SWINE FEVER VIRUS ON INTERLEUKIN-10 PRODUCTIONhttps://orcid.org/0000-0002-5099-3050ПершинА. C.PershinA. S.

Старший научный сотрудник, кандидат ветеринарных наук

Senior Researcher, Candidate of Science (Veterinary Medicine)

pershin@arriah.ruhttps://orcid.org/0000-0001-6482-7814ШевченкоИ. В.ShevchenkoI. V.

Научный сотрудник, кандидат биологических наук

Researcher, Candidate of Science (Biology)

shevchenko@arriah.ruhttps://orcid.org/0000-0002-5438-8026ИголкинА. С.IgolkinA. S.

Заведующий лабораторией, кандидат ветеринарных наук

Head of Laboratory, Candidate of Science (Veterinary Medicine)

igolkin_as@arriah.ruhttps://orcid.org/0000-0002-2072-6701АроноваЕ. В.AronovaYe. V.

Старший научный сотрудник, кандидат биологических наук

Senior Researcher, Candidate of Science (Biology)

aronova@arriah.ruhttps://orcid.org/0000-0001-8707-7710ВласоваН. Н.VlasovaN. N.

Главный научный сотрудник, доктор биологических наук

Senior Researcher, Doctor of Science (Biology)

vlasova_nn@arriah.ruФГБУ «ВНИИЗЖ», г. ВладимирРоссияFGBI "ARRIAH", VladimirRussian Federation201903102019032328Copyright © Першин А.C., Шевченко И.В., Иголкин А.С., Аронова Е.В., Власова Н.Н., 20192019Першин А.C., Шевченко И.В., Иголкин А.С., Аронова Е.В., Власова Н.Н.Pershin A.S., Shevchenko I.V., Igolkin A.S., Aronova Y.V., Vlasova N.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://veterinary.arriah.ru/jour/article/view/424

Характерной особенностью вируса африканской чумы свиней является способность избегать иммунного ответа организма хозяина, поражая макрофаги и размножаясь в  них. Кроме того, специфические антитела к  вирусу африканской чумы свиней его полностью не нейтрализуют. Важными факторами в протекании различных инфекционных вирусных патологий являются цитокины. Вирулентность изолятов вируса африканской чумы свиней может быть обусловлена возможностью регуляции экспрессии цитокинов макрофагами. Так, при сравнении продукции цитокинов макрофагами in vitro и in vivo установлено, что заражение низковирулентными изолятами вируса приводит к иммунному ответу с преобладанием цитокинов, вовлеченных в клеточный иммунитет, такими как ИНФ-α и ИЛ-12p40, в отличие от заражения высоковирулентными изолятами. Целью данной работы являлось изучение влияния вируса африканской чумы свиней на продукцию ИЛ-10 – плейотропного цитокина, ингибирующего синтез цитокинов и  проявляющего сильный противовоспалительный эффект. Для этого проводили экспериментальное заражение 12 поросят адаптированным к перевиваемой клеточной культуре изолятом вируса африканской чумы свиней Vero25 внутримышечно в дозе 10 ГАдЕ/гол. с последующим контрольным заражением выживших животных референтным изолятом вируса Аrm 07 в дозе 1000 ГАдЕ/гол. В течение всего опыта проводили термометрию и отбор проб крови для получения сыворотки. Определение содержания ИЛ-10 в сыворотке крови проводили с использованием тест-систем Invitrogen (Thermo Fisher, США). У погибших животных после заражения умеренно вирулентным вирусом в сыворотке крови наблюдался более высокий уровень ИЛ-10 (15,8–173 пг/мл) по сравнению с выжившими поросятами (4–5 пг/мл). Зависимости скорости появления специфических антител от уровня ИЛ-10 в сыворотке крови не установлено. Заметного влияния уровня содержания ИЛ-10 в сыворотке крови до заражения на выживаемость животных не установлено. Для установления причинно-следственной связи необходимы дальнейшие исследования, включающие изучение экспрессии различных цитокинов при заражении как низко-, так и высоковирулентными изолятами вируса.

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.

африканская чума свинейвирулентностьиммунологияинтерлейкин-10биопробаAfrican swine fevervirulenceimmunologyinterleukin-10bioassayReferencesВлияние пассивной иммунизации на клинические и патологоанатомические изменения у свиней, зараженных изолятом Мартинс-Крым 01/16 вируса АЧС / А. С. Першин, С. Г. Ремыга, И. В. Шевченко [и др.] // Ветеринария. – 2018. – № 1. – С. 25–31.Influence of passive immunization on clinical and pathological features of pig infection with isolate Martins-Crimea 01/16 ASFV [Vliyanie passivnoj immunizacii na klinicheskie i patologoanatomicheskie izmeneniya u svinej, zarazhennyh izolyatom Martins-Krym 01/16 virusa ACHS]. А. S. Pershin, S. G. Remyga, I. V. Shevchenko [et al.]. Veterinaria. 2018; 1: 2531 (in Russian).African swine fever virus infection induces tumor necrosis factor alpha production: implications in pathogenesis / M. Gómez del Moral, E. Ortuño, P. Fernández-Zapatero [et al.] // J. Virol. – 1999. – Vol. 73 (3). – P. 2173–2180; PMCID: PMC104462.African swine fever virus infection induces tumor necrosis factor alpha production: implications in pathogenesis. M. Gómez del Moral, E. Ortuño, P. Fernández-Zapatero [et al.]. J. Virol. 1999; 73 (3): 2173–2180; PMCID: PMC104462.African swine fever virus: a B cell-mitogenic virus in vivo and in vitro / H. Takamatsu, M. S. Denyer, C. Oura [et al.] // J. Gen. Virol. – 1999. – Vol. 80 (Pt. 6). – P. 1453–1461; DOI: 10.1099/0022-1317-80-6-1453.African swine fever virus: a B cell-mitogenic virus in vivo and in vitro. H. Takamatsu, M. S. Denyer, C. Oura [et al.]. J. Gen. Virol. 1999; 80 (Pt. 6): 1453–1461; DOI: 10.1099/0022-1317-80-6-1453.African swine fever: Expression of interleukin-1 alpha and tumour necrosis factor-alpha by pulmonary intravascular macrophages / L. Carrasco, A. Núñez, F. J. Salguero [et al.] // J. Comp. Pathol. – 2002. – Vol. 126 (2–3). – P. 194–201; DOI: 10.1053/jcpa.2001.0543.African swine fever: Expression of interleukin-1 alpha and tumour necrosis factor-alpha by pulmonary intravascular macrophages. L. Carrasco, A. Núñez, F. J. Salguero [et al.]. J. Comp. Pathol. 2002; 126 (2–3): 194–201; DOI: 10.1053/jcpa.2001.0543.Autocrine deactivation of macrophages in transgenic mice constitutively overexpressing IL-10 under control of the human CD68 promoter / R. Lang, R. L. Rutschman, D. R. Greaves, P. J. Murray // J. Immunol. – 2002. – Vol. 168 (7). – P. 3402–3411; DOI: 10.4049/jimmunol.168.7.3402.Autocrine deactivation of macrophages in transgenic mice constitutively overexpressing IL-10 under control of the human CD68 promoter. R. Lang, R. L. Rutschman, D. R. Greaves, P. J. Murray. J. Immunol. 2002; 168 (7): 3402–3411; DOI: 10.4049/jimmunol.168.7.3402.Biological properties of African swine fever virus Odintsovo 02/14 isolate and its genome analysis / A. A. Elsukova, I. V. Shevchenko, A. A. Varentsova [et al.] // Int. J. Environ. Agricult. Res. – 2017. – Vol. 3 (10). – P. 26–37; DOI: 10.25125/agriculture-journal-IJOEAR-OCT-2017-15.Biological properties of African swine fever virus Odintsovo 02/14 isolate and its genome analysis. A. A. Elsukova, I. V. Shevchenko, A. A. Varentsova [et al.]. Int. J. Environ. Agricult. Res. 2017; 3 (10): 26–37; DOI: 10.25125/ agriculture-journal-IJOEAR-OCT-2017-15.Blome S., Gabriel C., Beer M. Pathogenesis of African swine fever in domestic pigs and European wild boar // Virus Res. – 2013. – Vol. 173 (1). – P. 122–130; DOI: 10.1016/j.virusres.2012.10.026.Blome S., Gabriel C., Beer M. Pathogenesis of African swine fever in domestic pigs and European wild boar. Virus Res. 2013; 173 (1): 122–130; DOI: 10.1016/j.virusres.2012.10.026.Changes in macrophages in spleen and lymph nodes during acute African swine fever: expression of cytokines / F. J. Salguero, E. Ruiz-Villamor, M. J. Bautista [et al.] // Vet. Immunol. Immunopathol. – 2002. – Vol. 90 (1–2). – P. 11–22; DOI: 10.1016/S0165-2427(02)00225-8.Changes in macrophages in spleen and lymph nodes during acute African swine fever: expression of cytokines. F. J. Salguero, E. Ruiz-Villamor, M. J. Bautista [et al.]. Vet. Immunol. Immunopathol. 2002; 90 (1–2): 11–22; DOI: 10.1016/S0165-2427(02)00225-8.Characterization of the interaction of African swine fever virus with monocytes and derived macrophage subsets / G. Franzoni, S. P. Graham, S. D. Giudici [et al.] // Vet. Microbiol. – 2017. – Vol. 198. – P. 88–98; DOI: 10.1016/j.vetmic.2016.12.010.Characterization of the interaction of African swine fever virus with monocytes and derived macrophage subsets. G. Franzoni, S. P. Graham, S. D. Giudici [et al.]. Vet. Microbiol. 2017; 198: 88–98; DOI: 10.1016/j.vetmic.2016.12.010.Comparative analysis of clinical and biological characteristics of African swine fever virus isolates from 2013 year Russian Federation / N. N. Vlasova, A. A. Varentsova, I. V. Shevchenko [et al.] // British Microbiol. Res. J. – 2015. – Vol. 5 (3). – P. 203–215; DOI: 10.9734/bmrj/2015/12941.Comparative analysis of clinical and biological characteristics of African swine fever virus isolates from 2013 year Russian Federation. N. N. Vlasova, A. A. Varentsova, I. V. Shevchenko [et al.]. British Microbiol. Res. J. 2015; 5 (3): 203–215; DOI: 10.9734/bmrj/2015/12941.Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome of Ebola virus-infected patients / S. Baize, E. M. Leroy, M. C. Georges-Courbot [et al.] // Nat. Med. – 1999. – Vol. 5 (4). – P. 423–426; DOI: 10.1038/7422.Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome of Ebola virus-infected patients. S. Baize, E. M. Leroy, M. C. Georges-Courbot [et al.]. Nat. Med. 1999; 5 (4): 423–426; DOI: 10.1038/7422.Evolution of African swine fever virus genes related to evasion of host immune response / M. Frączyk, G. Woźniakowski, A. Kowalczyk [et al.] // Vet. Microbiol. – 2016. – Vol. 193. – P. 133–144; DOI: 10.1016/j.vetmic.2016.08.018.Evolution of African swine fever virus genes related to evasion of host immune response. M. Frączyk, G. Woźniakowski, A. Kowalczyk [et al.]. Vet. Microbiol. 2016; 193: 133–144; DOI: 10.1016/j.vetmic.2016.08.018.Expression at mRNA level of cytokines and A238L gene in porcine blood-derived macrophages infected in vitro with African swine fever virus (ASFV) isolates of different virulence / S. Gil, M. Spagnuolo-Weaver, A. Canals [et al.] // Arch. Virol. – 2003. – Vol. 148 (11). – P. 2077–2097; DOI: 10.1007/ s00705-003-0182-x.Expression at mRNA level of cytokines and A238L gene in porcine blood-derived macrophages infected in vitro with African swine fever virus (ASFV) isolates of different virulence. S. Gil, M. Spagnuolo-Weaver, A. Canals [et al.]. Arch. Virol. 2003; 148 (11): 2077–2097; DOI: 10.1007/s00705-003- 0182-x.Genetic variation among African swine fever genotype II viruses, Eastern and Central Europe / C. Gallardo, J. Fernández-Pinero, V. Pelayo [et al.] // Emerg. Infect. Dis. – 2014. – Vol. 20 (9). – P. 1544–1547; DOI: 10.3201/eid2009.140554.Genetic variation among African swine fever genotype II viruses, Eastern and Central Europe. C. Gallardo, J. Fernández-Pinero, V. Pelayo [et al.]. Emerg. Infect. Dis. 2014; 20 (9): 1544–1547; DOI: 10.3201/eid2009.140554.IL-10 enhances expression of the IL-2 receptor alpha chain on T cells / S. B. Cohen, P. D. Katsikis, M. Feldmann, M. Londei // Immunology. – 1994. – Vol. 83 (3). – P. 329–332; PMCID: PMC1415032.IL-10 enhances expression of the IL-2 receptor alpha chain on T cells. S. B. Cohen, P. D. Katsikis, M. Feldmann, M. Londei. Immunology. 1994; 83 (3): 329–332; PMCID: PMC1415032.IL-10, an inflammatory/inhibitory cytokine, but not always / P. Conti, D. Kempuraj, K. Kandere [et al.] // Immunol Lett. – 2003. – Vol. 86 (2). – P. 123–129; DOI: 10.1016/s0165-2478(03)00002-6.IL-10, an inflammatory/inhibitory cytokine, but not always. P. Conti, D. Kempuraj, K. Kandere [et al.]. Immunol Lett. 2003; 86 (2): 123–129; DOI: 10.1016/s0165-2478(03)00002-6.In vivo depletion of CD8+ T lymphocytes abrogates protective immunity to African swine fever virus / C. A. Oura, M. S. Denyer, H. Takamatsu, R. M. Parkhouse // J. Gen. Virol. – 2005. – Vol. 86 (Pt. 9). – Р. 2445–2450; DOI: 10.1099/vir.0.81038-0.In vivo depletion of CD8+ T lymphocytes abrogates protective immunity to African swine fever virus. C. A. Oura, M. S. Denyer, H. Takamatsu, R. M. Parkhouse. J. Gen. Virol. 2005; 86 (Pt. 9): 2445–2450; DOI: 10.1099/ vir.0.81038-0.Induction of IL-10 and inhibition of experimental arthritis are specific features of microbial heat shock proteins that are absent for other evolutionarily conserved immunodominant proteins / B. Prakken, U. Wendling, R. van der Zee [et al.] // J. Immunol. – 2001. – Vol. 167 (8). – P. 4147–4153; DOI: 10.4049/jimmunol.167.8.4147.Induction of IL-10 and inhibition of experimental arthritis are specific features of microbial heat shock proteins that are absent for other evolutionarily conserved immunodominant proteins. B. Prakken, U. Wendling, R. van der Zee [et al.]. J. Immunol. 2001; 167 (8): 4147–4153; DOI: 10.4049/ jimmunol.167.8.4147.Inflammatory cytokines in animal health and disease / M. Murtaugh, M. J. Baarsch, Y. Zhou [et al.] // Vet. Immunol. Immunopathol. – 1996. – Vol. 54 (1–4). – P. 45–55; DOI: 10.1016/S0165-2427(96)05698-X.Inflammatory cytokines in animal health and disease. M. Murtaugh, M. J. Baarsch, Y. Zhou [et al.]. Vet. Immunol. Immunopathol. 1996; 54 (1–4): 45–55; DOI: 10.1016/S0165-2427(96)05698-X.Influence of age and dose of African swine fever virus infections on clinical outcome and blood parameters in pigs / J. Post, E. Weesendorp, M. Montoya, W. L. Loeffen // Viral Immunol. – 2017. – Vol. 30 (1). – Р. 58–69; DOI: 10.1089/vim.2016.0121.Influence of age and dose of African swine fever virus infections on clinical outcome and blood parameters in pigs. J. Post, E. Weesendorp, M. Montoya, W. L. Loeffen. Viral Immunol. 2017; 30 (1): 58–69; DOI: 10.1089/ vim.2016.0121.Interleukin (IL)-10 inhibits nuclear factor kappa B (NF kappa B) activation in human monocytes IL-10 and IL-4 suppress cytokine synthesis by different mechanisms / P. Wang, P. Wu, M. I. Siegel [et al.] // J. Biol. Chem. – 1995. – Vol. 270 (16). – P. 9558–9563; DOI: 10.1074/jbc.270.16.9558.Interleukin (IL)-10 inhibits nuclear factor kappa B (NF kappa B) activation in human monocytes IL-10 and IL-4 suppress cytokine synthesis by different mechanisms. P. Wang, P. Wu, M. I. Siegel [et al.]. J. Biol. Chem. 1995; 270 (16): 9558–9563; DOI: 10.1074/jbc.270.16.9558.Interleukin-10 and the interleukin-10 receptor / K. W. Moore, R. de Waal Malefyt, R. L. Coffman, A. O’Garra // Ann. Rev. Immunol. – 2001. – Vol. 19. – Р. 683–765; DOI: 10.1146/annurev.immunol.19.1.683.Interleukin-10 and the interleukin-10 receptor. K. W. Moore, R. de Waal Malefyt, R. L. Coffman, A. O’Garra. Ann. Rev. Immunol. 2001; 19: 683–765; DOI: 10.1146/annurev.immunol.19.1.683.Manipulating IL-10 signalling blockade for better immunotherapy / G. Ni, T. Wang, S. Walton [et al.] // Cell. Immunol. – 2015. – Vol. 293 (2). – P. 126–129; DOI: 10.1016/j.cellimm.2014.12.012.Manipulating IL-10 signalling blockade for better immunotherapy. G. Ni, T. Wang, S. Walton [et al.]. Cell. Immunol. 2015; 293 (2): 126–129; DOI: 10.1016/j.cellimm.2014.12.012.Markedly elevated levels of interferon (IFN)-γ, IFN-α, interleukin (IL)-2, IL-10, and tumor necrosis factor-α associated with fatal Ebola virus infection / F. Villinger, P. E. Rollin, S. S. Brar [et al.] // J. Infect. Dis. – 1999. – Vol. 179 (Suppl. 1). – P. 188–191; DOI: 10.1086/514283.Markedly elevated levels of interferon (IFN)-γ, IFN-α, interleukin (IL)-2, IL-10, and tumor necrosis factor-α associated with fatal Ebola virus infection. F. Villinger, P. E. Rollin, S. S. Brar [et al.]. J. Infect. Dis. 1999; 179 (Suppl. 1): 188–191; DOI: 10.1086/514283.Molecular characterization and SNP development for the porcine IL6 and IL10 genes / E. Daniłowicz, M. Akouchekian, C. Drogemuller [et al.] // Anim. Biotechnol. – 2008. – Vol. 19 (3). – P. 159–165; DOI: 10.1080/10495390802088621.Molecular characterization and SNP development for the porcine IL6 and IL10 genes. E. Daniłowicz, M. Akouchekian, C. Drogemuller [et al.]. Anim. Biotechnol. 2008; 19 (3): 159–165; DOI: 10.1080/10495390802088621.Mosser D. M. The many faces of macrophage activation // J. Leukoc. Biol. – 2003. – Vol. 73 (2). – P. 209–212; DOI: 10.1189/jlb.0602325.Mosser D. M. The many faces of macrophage activation. J. Leukoc. Biol. 2003; 73 (2): 209–212; DOI: 10.1189/jlb.0602325.Pathology of African swine fever: the role of monocytemacrophage / J. C. Gómez-Villamandos, M. J. Bautista, P. J. Sánchez-Cordón, L. Carrasco // Virus. Res. – 2013. – Vol. 173 (1). – P. 140–149; DOI: 10.1016/j. virusres.2013.01.017.Pathology of African swine fever: the role of monocyte-macrophage. J. C. Gómez-Villamandos, M. J. Bautista, P. J. Sánchez-Cordón, L. Carrasco. Virus. Res. 2013; 173 (1): 140–149; DOI: 10.1016/j.virusres.2013.01.017.Peters C. J. Viral hemorrhagic fevers // Viral Pathogenesis / ed. N. Nathanson [et al.]. – Philadelphia: Lippincott-Raven, 1997. – P. 779–799.Peters C. J. Viral hemorrhagic fevers. Viral Pathogenesis. ed. N. Nathanson [et al.]. Philadelphia: Lippincott-Raven, 1997; 779–799.Regulatory activity of autocrine IL-10 on dendritic cell functions / S. Corinti, C. Albanesi, A. la Sala [et al.] // J. Immunol. – 2001. – Vol. 166 (7). – P. 4312–4318; DOI: 10.4049/jimmunol.166.7.4312.Regulatory activity of autocrine IL-10 on dendritic cell functions. S. Corinti, C. Albanesi, A. la Sala [et al.]. J. Immunol. 2001; 166 (7): 4312–4318; DOI: 10.4049/jimmunol.166.7.4312.The low-virulent African swine fever virus (ASFV/NH/P68) induces enhanced expression and production of relevant regulatory cytokines (IFNα, TNFα and IL12p40) on porcine macrophages in comparison to the highly virulent ASFV/L60 / S. Gil, N. Sepúlveda, E. Albina [et al.] // Arch. Virol. – 2008. – Vol. 153 (10). – P. 1845–1854; DOI: 10.1007/s00705-008- 0196-5.The low-virulent African swine fever virus (ASFV/NH/P68) induces enhanced expression and production of relevant regulatory cytokines (IFNα, TNFα and IL12p40) on porcine macrophages in comparison to the highly virulent ASFV/L60. S. Gil, N. Sepúlveda, E. Albina [et al.]. Arch. Virol. 2008; 153 (10): 1845–1854; DOI: 10.1007/s00705-008-0196-5.The pathogenic role of pulmonary intravascular macrophages in acute African swine fever / L. Carrasco, F. C. de Lara, J. C. Gómez-Villamandos [et al.] // Res. Vet. Sci. – 1996. – Vol. 61 (3). – P. 193–198; PMID: 8938846.The pathogenic role of pulmonary intravascular macrophages in acute African swine fever. L. Carrasco, F. C. de Lara, J. C. Gómez-Villamandos [et al.]. Res. Vet. Sci. 1996; 61 (3): 193–198; PMID: 8938846.Vaccination against tuberculosis: how can we better BCG? / J. M. Pitt, S. Blankley, H. McShane, A. O’Garra // Microb. Pathog. – 2013. – Vol. 58. – P. 2–16; DOI: 10.1016/j.micpath.2012.12.002.Vaccination against tuberculosis: how can we better BCG? J. M. Pitt, S. Blankley, H. McShane, A. O’Garra. Microb. Pathog. 2013; 58: 2–16; DOI: 10.1016/j.micpath.2012.12.002.Wardley R. C. Effect of African swine fever on lymphocyte mitogenesis // Immunology. – 1982. – Vol. 46 (1). – P. 215–220; PMCID: PMC1555335.Wardley R. C. Effect of African swine fever on lymphocyte mitogenesis. Immunology. 1982; 46 (1): 215–220; PMCID: PMC1555335.

The authors declare that there are no conflicts of interest present.