Pathology and Clinics of Naturally Occurring Low-Virulence Variants of African Swine Fever Emerged in Domestic Pigs in the South Caucasus.

Shortly after the establishment of African swine fever virus (ASFV) genotype II in 2007, cases of acute fatal infection were observed. However, after several years of circulation in the Eurasian region, the clinical signs of the disease changed. Currently, this disease can occur acutely, subclinically, chronically, or asymptomatically. Cases of the complete recovery of infected pigs, and the disappearance of ASFV from their tissues and secretions have been described. This form of the disease first appeared in Armenia at the end of 2011. This virus was described and identified as the Dilijan2011IMB strain. The goal of our research was to study the main features of clinical, pathological, immunological, virological, and genetic parameters involved in the development of new forms of African swine fever (ASF). Chronic ASF was characterized with low titers of the virus and a decrease in the intensity of hemadsorption. Additionally, a reduced intensity in clinical symptoms and pathoanatomical results was noted. The absolute, but not the relative number of immune cells changes; the neutropenia (in bone marrow and spleen), lymphopenia (in bone marrow), lymphocytosis (only in spleen), lymphoid cell depletion (in bone marrow), and pancytopenia (in bone marrow) observed in the chronic form of ASF were less pronounced compared to in the acute form. When comparing the late stage of chronic ASF to the acute form, the key cytological indicators in the spleen, lymph nodes, and blood were less severe in the chronic stage. Bone marrow failure in the chronic form, expressed in a pronounced decrease in all cell types, generally coincided with the data in the acute form of ASF. The same data were obtained after assessing serum TNF-alpha levels. Thus, we can conclude that the chronic form of ASF occurs due to a less pronounced immune response, as well as a decrease in virus titers in the blood and tissues of infected pigs.

The Effect of Low-Energy Laser-Driven Ultrashort Pulsed Electron Beam Irradiation on Erythropoiesis and Oxidative Stress in Rats.

Anemia is a commonly observed consequence of whole-body exposure to a dose of X-ray or gamma irradiation of the order of the mean lethal dose in mammals, and it is an important factor for the determination of the survival of animals. The aim of this study was to unravel the effect of laser-driven ultrashort pulsed electron beam (UPEB) irradiation on the process of erythropoiesis and the redox state in the organism. Wistar rats were exposed to laser-driven UPEB irradiation, after which the level of oxidative stress and the activities of different antioxidant enzymes, as well as blood smears, bone marrow imprints and sections, erythroblastic islets, hemoglobin and hematocrit, hepatic iron, DNA, and erythropoietin levels, were assessed on the 1st, 3rd, 7th, 14th, and 28th days after irradiation. Despite the fact that laser-driven UPEB irradiation requires quite low doses and repetition rates to achieve the LD50 in rats, our findings suggest that whole-body exposure with this new type of irradiation causes relatively mild anemia in rats, with subsequent fast recovery up to the 28th day. Moreover, this novel type of irradiation causes highly intense processes of oxidative stress, which, despite being relatively extinguished, did not reach the physiologically stable level even at the 28th day after irradiation due to the violations in the antioxidant system of the organism.

Patterns of alveolar macrophage activation upon attenuated and virulent African swine fever viruses in vitro.

The pattern of porcine alveolar macrophage (AM) activation upon classical stimuli of two strains of African swine fever (ASF) viruses, an attenuated ASFV-BA71V and virulent ASFV-Georgia2007 were investigated. In an in vitro experiment ASFV-Georgia2007-infected AM showed M1 polarization pattern different from the one induced by classical stimuli. Altered morphology, appearance of binuclear cells, decreased synthesis of IFN-alpha as well as IFN-epsilon was observed compared with attenuated ASFV-BA71V, and decreased synthesis of IFN-omega compared with intact cells. However, CD68 level did not significantly differ between alveolar macrophage populations infected by ASFV-Georgia2007 and control group, while both LPS/IFN-gamma stimulation and non-pathogenic ASFV-BA71V virus increased the level of CD68 soluble receptor. AM infection with ASFV-Georgia2007 resulted in remarkable DNA proliferation whereas LPS/IFN-gamma and ASFV-BA71V induced less expressed DNA proliferation in activated cells. The higher value of nitric oxide was obvious in the cells infected with ASFV-BA71V, compared to ASFV-Georgia2007 and LPS/IFN-gamma activated cells. In conclusion, pattern of activation of alveolar macrophages induced by ASFV-Georgia2007 virus differs from the one expressed in LPS/IFN-gamma- and ASFV-BA71V-activated cells. ASFV-BA71V and LPS/IFN-gamma share similar antiviral response of porcine AM. Therefore we assume that wild type virulent ASFV can partially down regulate antiviral response of AM and conclude that evolutionary decrease of virulence in ASFV is related to alterations of control of the host cell antiviral response.

Cardiopathology in acute African Swine Fever

The present study describes the gross, histopathologic lesions of the heart arising in pigs infected with acute African Swine Fever (ASF) and their biochemical profile. Ten pigs were infected by intramuscular injection of ASF virus (Georgia 2007). Selected heart samples were submitted for histopathological examination and Hematoxylin-Basic Fuchsin-Picric Acid (HBFP) staining. Enzymatic abnormalities were evaluated by measurement of main cardiac markers, whose activity increased during the early stage of infection, with histopathological changes occurring later. Minor myocardial haemorrhages were first observed at four days post infection (dpi), and were noted in all pigs by six dpi. Early vascular response to infection was manifested as increased capillary permeability leading to diapedesis and the retention of blood cells in myocardial tissue. The terminal stage of the disease was characterised by massive haemorrhages caused by the rupture of large vessels. Substantial ischemic areas were detected by HBFP staining at the terminal stages of ASF.

Association of hemophagocytic lymphohistiocytosis with kidney lesions in acute African swine fever virus infection

Glomerulonephritis due to African swine fever (ASF) is well documented. However, there is absence of good understanding of mechanisms involved in the development of pathology development. This study examines glomerulonephritis in association with acute infection induced by II genotype (Georgia 2007) of ASF virus. Taken together, the results of urinary analysis and the renal histological analysis led to the diagnosis of diffuse endocapillary proliferative glomerulonephritis with severe tubular injury associated with acute ASF (Georgia 2007). According to the pathogenesis, we have found that the diffuse endocapillary proliferative glomerulonephritis associated with the acute ASF develops with a delay of one to two days compared to development of hemophagocytic lymphohistiocytosis. The diagnosis of endocapillary proliferative glomerulonephritis confirms the characteristic of pathological changes in the composition of urine and urine sediment. The development of acute proliferative glomerulonephritis begins at 3 dpi, and finished at 4­6 dpi with the development of tubular necrosis. Our study demonstrates local macrophage proliferation. Local proliferation may be an important mechanism for amplifying macrophage-mediated renal injury. We have shown that the development of diffuse acute proliferative glomerulonephritis during ASF does not coincide with the presence of the virus in the blood or kidney tissues, but coincides with the developmental of ASFV derived hemophagocytic lymphohistiocytosis. The development of hemophagocytic lymphonocytosis also begins at least at 2­3 dpi and continues up to the terminal stage of the disease.