African Swine Fever Virus Infection of Bone Marrow: Lesions and Pathogenesis

Abstract

The effects of African swine fever (ASF) virus infection on bone marrow hematopoiesis and microenvironment were determined by studying the sequential development of ultrastructural lesions of bone marrow and blood cell changes. Eight pigs (two pigs/infected group) were inoculated by intramuscular route with 10(5) 50% hemadsorbing doses (HAD50) of the Malawi'83 ASF virus isolate. Two uninfected pigs were used as controls. Ultrastructural changes developed by day 3 postinoculation (PI), persisted through day 7 PI, and were characterized by activation of macrophages. From day 5 PI, viral replication was observed in monocytes/macrophages, reticular cells, immature neutrophils, and promonocytes. Also viral replication was detected in megakaryocytes, endothelial cells, and pericytes at day 7 PI. Vascular alterations consisted of activation of sinusoidal endothelial cells, intravascular coagulation, and fibrin strands interspersed among microenvironment and hematopoietic cells. No significant changes were observed in total white blood cells counts, percentage of monocytes, and platelet counts; however, severe lymphopenia and neutrophilia were detected from day 3 PI. Results of this experiment indicate that there is increased hematopoiesis in bone marrow during acute ASF, coinciding with macrophage activation. Neither vascular changes nor viral replication in different bone marrow cell populations gave rise to impaired bone marrow function. Increased hematopoiesis would exert a positive influence by preventing the early onset of thrombocytopenia and would exert a negative influence by stimulating the spread of the virus via neutrophils. Increased hematopoiesis would be unable to compensate for the lymphopenia.

Evidence of hemolysis in pigs infected with highly virulent African swine fever virus

“…The clinical signs of experimental infection have some differences from those in cited researches with Malawi’ 83 ASFV isolate [9] and our previous study [10]. …”

Ultrastructural Findings in Lymph Nodes from Pigs Suffering from Naturally Occurring Postweaning Multisystemic Wasting Syndrome

“…As a whole, the observed changes are indicative of secretory activation and inflammation. 5 Most of these ultrastructural changes were associated with the presence of VLPs in the cytoplasm of affected cells (and occasionally in the nucleus), which were similar to those observed with other viruses such as African swine fever, 5 classical swine fever, 6 and rubella virus. 15 According to the literature, viral factories (VFs) refer to aggregates of viral particles of different shapes and sizes, which represent viral maturation structures that induce changes in cellular organization.…”

“…PCV2 VFs were also surrounded by proliferated and degenerated mitochondria; this feature has also been described in some DNA viruses such as ASFV, where VFs are observed next to these organelles. 5 Of interest, immature PCV2-like particles were also observed within mitochondria, suggesting that the virus might replicate within this organelle. Viral replication within mitochondria is not apparently described in the literature for other viruses; although some RNA viruses can use the mitochondrial membrane for replication, they are not present within the organelle.…”

Species-Specific Variation in RELA Underlies Differences in NF-κB Activity: a Potential Role in African Swine Fever Pathogenesis

“…This is thought, in part, to be the result of a proinflammatory cytokine storm driven by infected macrophages (9,15,16,(42)(43)(44)56). Initiation of a systemic inflammatory response results in severe hematological and vascular perturbations, ultimately leading to cardiovascular collapse in a manner not dissimilar to septic shock (3,17,18,20,21,40,52,53). In addition to hemorrhage, severe widespread apoptosis of infected macrophages and uninfected lymphocytes is a prominent feature of the disease; this is also likely related to markedly elevated proinflammatory cytokine levels (19,33,37,43).…”