Vascular endothelial growth factor (VEGF), produced by feline infectious peritonitis (FIP) virus-infected monocytes and macrophages, induces vascular permeability and effusion in cats with FIP

Abstract

Feline infectious peritonitis virus (FIPV) causes a fatal disease called FIP in Felidae. The effusion in body cavity is commonly associated with FIP. However, the exact mechanism of accumulation of effusion remains unclear. We investigated vascular endothelial growth factor (VEGF) to examine the relationship between VEGF levels and the amounts of effusion in cats with FIP. Furthermore, we examined VEGF production in FIPV-infected monocytes/macrophages, and we used feline vascular endothelial cells to examine vascular permeability induced by the culture supernatant of FIPV-infected macrophages. In cats with FIP, the production of effusion was related with increasing plasma VEGF levels. In FIPV-infected monocytes/macrophages, the production of VEGF was associated with proliferation of virus. Furthermore, the culture supernatant of FIPV-infected macrophages induced hyperpermeability of feline vascular endothelial cells. It was suggested that vascular permeability factors, including VEGF, produced by FIPV-infected monocytes/macrophages might increase the vascular permeability and the amounts of effusion in cats with FIP.

Genome-wide analysis of differentially expressed genes and the modulation of PEDV infection in Vero E6 cells

“…Todd Wuest et al observed that the herpes simplex virus-1 drived the expression of VEGFA by mimicking the function of the VEGFA promoter [55]. Tomomi Takano also found that the production of VEGF was associated with the proliferation of Feline infectious peritonitis virus [56]. MHY1485 is an activator of the mTOR signaling pathway while the PP242 acts as an inhibitor.…”

An update on feline infectious peritonitis: Virology and immunopathogenesis

“…The pyogranuloma is also strongly associated with edema and the effusion of large volumes of a proteinaceous fluid that is rich in plasma proteins, hemoglobin breakdown products, inflammatory proteins of many types and activated clotting factors. The factors responsible for this outpouring of fluid have not been identified fully, but at least one of these factors appears to be vascular endothelial growth factor (VEGF; Takano et al, 2011a). This is produced by FIPV infected monocytes and macrophages.…”

Feline Coronaviruses

“…Moreover, it has been suggested that the increased expression of enzymes such as matrix metalloproteinase-9 by the activated monocytes contributes to endothelial barrier dysfunction and subsequent extravasation of monocytes (Kipar and Meli, 2014;Kipar et al, 2005). Furthermore, the production of vascular endothelial growth factor produced in FIPV-infected monocytes and macrophages was proposed to induce increased vascular permeability and hence effusion in body cavities (Takano et al, 2011). Although leukocytes are not susceptible to FIPV infection, they appear to become activated during FIPV infection by as-yet-unknown mechanisms, thereby probably contributing to endothelial cell damage and the development of FIP lesions .…”

“…Deletions in the 7b gene have also been proposed to play an important role in FIP development. However, consecutive analyses revealed that deletions in 7b primarily evolve during cell culture adaptation and are associated with loss of virulence (Herrewegh et al, 1995b(Herrewegh et al, , 1998Takano et al, 2011). The existence of deletions in the 7b gene in naturally occurring FECVs argues against a major involvement of mutations in 7b in FIP development (Lin et al, 2009).…”