Porcine circovirus 2 (PCV2) increases the expression of endothelial adhesion/junction molecules

Abstract

Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus disease, a complex multisystem syndrome in domestic pigs. Despite the significant economic losses caused by porcine circovirus disease, the mechanisms of pathogenesis underlying the clinical findings remain largely unclear. As various reports have highlighted the potential key role of vascular lesions in the pathogenesis of porcine circovirus disease, the aim of this work was to investigate effects of PCV2 infection on vascular endothelial cells, focusing on cell viability and expression of adhesion/junction molecules. PCV2 infection reduced endothelial cell viability, while viral infection did not affected the viability of several other classical cell lines. Also, PCV2 infection in endothelial cells displayed a dual/biphasic effect: initially, infection increased ICAM-1 expression, which can favor leukocyte recruitment and emigration to tissues and possibly inducing characteristic porcine circovirus disease inflammatory lesions; then, secondarily, infection caused an increase in zonula occludens 1 tight junction protein (ZO-1) expression, which in turn can result in difficulties for cell traffic across the endothelium and a potential impairment the immune response in peripheral tissues. These virus-induced endothelial changes could directly impact the inflammatory process of porcine circovirus disease and associated vascular/immune system disturbances. Data suggest that, among the wide range of effects induced by PCV2 on the host, endothelial modulation can be a pivotal process which can help to explain PCV2 pathogenesis in some porcine circovirus disease presentations.

Current Understanding of the Pathogenesis of Porcine Circovirus 3

“…Reactome pathway analysis has shown that following PCV3 infection, proteins associated with adhesion and cell junction organization were expressed [21]. In PCV2, intercellular adhesion molecule 1 (ICAM-1) was upregulated in the infected endothelial cells, which might modulate the leucocyte infiltration into tissues leading to vascular lesions [22]. Whether ICAM-1 might play an important role in PCV3-induced vascular damage should be further investigated.…”

Porcine circovirus type 2 upregulates endothelial-derived IL-8 production in porcine iliac artery endothelial cells via the RIG-I/MDA-5/MAVS/JNK signaling pathway

“…In addition, endothelial cell disfunction and vascular system disorders are also the main symptoms of porcine circovirus disease (PCVD) [2]. The PCV2-infected endothelial cells can regulate leukocyte migration, inflammatory responses [3] and induce the production of endothelial-derived IL-8 [4]. It is reported that endothelial-derived IL-8, with a pentapeptide AVLPR extension at the NH2-terminus [5], has different biological function compared with monocyte-derived IL-8 [6].…”

Change in the immune function of porcine iliac artery endothelial cells infected with porcine circovirus type 2 and its inhibition on monocyte derived dendritic cells maturation

“…For example, PCVD-infected swine exhibit blood hypercoagulation, petechiae and vasculitis associated with lymph node atrophy, organ failure with ischemic, necrotic lesions, and brain hemorrhage [ 7 , 8 ]. PCV2 not only causes severe degeneration of endothelial cells (ECs) [ 9 ], but also stimulates procoagulant activity in ECs and leads to vascular injury [ 8 , 10 ], which indicates that the hemostatic system and ECs play an important role in the immune pathogenesis of PCV2. Naturally infected PCV2 swine exhibit endarteritis, and the PCV2 antigen has been detected in vascular endothelial cells (VECs) in infected swine [ 11 ].…”

“…PCV2 has a direct cytopathic effect on tunica media myocytes of small- and medium-sized arteries as well as the endothelium [ 12 ]. Moreover, PCV2 infection can influence VEC function by upregulating the expression of endothelial adhesion and junction molecules [ 10 ], and Th1 and Th2 cytokines [ 13 ].…”