VEGF Upregulation in Viral Infections and Its Possible Therapeutic Implications

Abstract

Several viruses are recognized as the direct or indirect causative agents of human tumors and other severe human diseases. Vascular endothelial growth factor (VEGF) is identified as a principal proangiogenic factor that enhances the production of new blood vessels from existing vascular network. Therefore, oncogenic viruses such as Kaposi’s sarcoma herpesvirus (KSHV) and Epstein-Barr virus (EBV) and non-oncogenic viruses such as herpes simplex virus (HSV-1) and dengue virus, which lack their own angiogenic factors, rely on the recruitment of cellular genes for angiogenesis in tumor progression or disease pathogenesis. This review summarizes how human viruses exploit the cellular signaling machinery to upregulate the expression of VEGF and benefit from its physiological functions for their own pathogenesis. Understanding the interplay between viruses and VEGF upregulation will pave the way to design targeted and effective therapeutic approaches for viral oncogenesis and severe diseases.

SARS-CoV-2 infection: The role of cytokines in COVID-19 disease

“…Severe inflammation and the associated immune responses induce the apoptosis of epithelial and endothelial cells, increasing the production of VEGF and exacerbating edema and the extravasation of immune cells [188]. The pathogenic effects of this factor are related to its action on vascular permeability and neoangiogenesis [189,190]. VEGF hyper-regulation is observed in various viral infections, and attempts have been made to stimulate this factor by using VEGF homologs present in some viruses or by activating inflammatory mediators that trigger the overexpression of VEGF [189].…”

“…The pathogenic effects of this factor are related to its action on vascular permeability and neoangiogenesis [189,190]. VEGF hyper-regulation is observed in various viral infections, and attempts have been made to stimulate this factor by using VEGF homologs present in some viruses or by activating inflammatory mediators that trigger the overexpression of VEGF [189].…”

Epigenetic regulator miRNA pattern differences among SARS-CoV, SARS-CoV-2 and SARS-CoV-2 world-wide isolates delineated the mystery behind the epic pathogenicity and distinct clinical characteristics of pandemic COVID-19

“…which can be hijacked by viruses for their efficient replication, pre-mRNA processing and translation (Figure 5A). These host miRNAs might also try to reduce some host induced inflammatory responses to prevent acute lung damage by targeting IGF1 signaling (Li et al, 2019), VEGF signaling (Alkharsah, 2018), PAR1 signaling (Heuberger and Schuepbach, 2019), integrin signaling (Teoh et al, 2015), TGF-beta signaling (Denney et al, 2018), TRAIL signaling (Cummins and Badley, 2009), etc (Figure 5A). Some signaling pathways like-CXCR4 signaling (Arnolds and Spencer, 2014), TGF-beta signaling (Denney et al, 2018), mTOR signaling (Le Sage et al, 2016), PI3K-Akt signaling (Diehl and Schaal, 2013), etc.…”

“…To identify which pathways are associated with SARS-CoV and SARS-CoV infection, we have performed the gene ontology (GO) and pathway functional enrichment of the targeted genes using different tools. This reveals a myriad of significant functions and pathways involved in host immune responses, like-Wnt signaling (Ljungberg et al, 2019), MAPK signaling (Kimura et al, 2013), T cell-mediated immunity (Channappanavar et al, 2014), autophagy (Yordy and Iwasaki, 2011), FGF receptor binding (van Asten et al, 2018), TGF-beta signaling (Denney et al, 2018), VEGF signaling (Alkharsah, 2018), ErbB signaling (Zheng et al, 2014), mTOR signaling (Le Sage et al, 2016), TNF-alpha signaling (Kimura et al, 2013), etc are particularly targeted by SARS-CoV-2 (Figure 7A-7E).…”

Vaccines and Therapeutics Against Hantaviruses

“…Increased capillary leakage due to hantaviral infection is the basic pathogenic feature for both HFRS and HCPS. Therefore, treatment strategies improving microvascular endothelial cell function seem to be feasible in mitigating disease severity and reducing mortality (Alkharsah, 2018). Hantavirus-disturbed vascular function is a multifactorial event whose complicated mechanisms still need to be elucidated, and two kinds of hypothesis have been developed.…”