Exploitation of receptor tyrosine kinases by viral-encoded growth factors

Lateef, Zabeen; Wise, Lyn M.

doi:10.1080/08977194.2018.1520229

Cited by 10 publications

(8 citation statements)

References 235 publications

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“…Vascular endothelial growth factors (VEGFs) control blood vessel formation and are critical for development and tissue repair [161]. The mammalian VEGF family comprises of five ligands that each interacts with one or more high-affinity VEGF receptors (VEGFRs).…”

Section: Vvegfmentioning

confidence: 99%

“…The vVEGF also likely contributes to environmental spread, as scab formation was reduced in lesions induced by the virus lacking this gene [168]. The vVEGFs show extensive genetic diversity from, but the high structural similarity to, the mammalian VEGFs [161,170]. Although the crystal structure of the ORFV protein shows retention of the characteristic homodimeric cysteine knot motif [171], conformational differences are evident in loop regions associated with VEGFR binding, and within the glycosylated C-terminus [165,170,172].…”

Section: Vvegfmentioning

confidence: 99%

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Deriving Immune Modulating Drugs from Viruses—A New Class of Biologics

Yaron

Zhang

Guo

et al. 2020

JCM

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Viruses are widely used as a platform for the production of therapeutics. Vaccines containing live, dead and components of viruses, gene therapy vectors and oncolytic viruses are key examples of clinically-approved therapeutic uses for viruses. Despite this, the use of virus-derived proteins as natural sources for immune modulators remains in the early stages of development. Viruses have evolved complex, highly effective approaches for immune evasion. Originally developed for protection against host immune responses, viral immune-modulating proteins are extraordinarily potent, often functioning at picomolar concentrations. These complex viral intracellular parasites have “performed the R&D”, developing highly effective immune evasive strategies over millions of years. These proteins provide a new and natural source for immune-modulating therapeutics, similar in many ways to penicillin being developed from mold or streptokinase from bacteria. Virus-derived serine proteinase inhibitors (serpins), chemokine modulating proteins, complement control, inflammasome inhibition, growth factors (e.g., viral vascular endothelial growth factor) and cytokine mimics (e.g., viral interleukin 10) and/or inhibitors (e.g., tumor necrosis factor) have now been identified that target central immunological response pathways. We review here current development of virus-derived immune-modulating biologics with efficacy demonstrated in pre-clinical or clinical studies, focusing on pox and herpesviruses-derived immune-modulating therapeutics.

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Section: Vvegfmentioning

confidence: 99%

Section: Vvegfmentioning

confidence: 99%

Deriving Immune Modulating Drugs from Viruses—A New Class of Biologics

Yaron

Zhang

Guo

et al. 2020

JCM

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“…To perform their functions, GFs can activate multiple receptors with structural similarities, and growth factor receptors (GFR) can have multiple ligands with structural and functional similarities, the only exception being HGF and its receptor Met, which are exclusive to each other [ 70 ]. However, there is increasing evidence that viruses can interact with RTKs, modulating their activity to increase cell entry and promote replication into the host [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

“…The biological effects of VEGF are mediated by three RTKs that are expressed in areas of the body where fluid balance is critically regulated and may be localized, such as the choroid plexus of the brain, or systemically, such as resistance vessels [ 73 ]. In brief, VEGFR-1 is mainly expressed in monocytes, macrophages, vascular smooth muscle cells, and neuronal cells; VEGFR-2 in endothelial cells; and VEGFR-3 in the lymphatic endothelium [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

The Role of Growth Factors in the Pathogenesis of Dengue: A Scoping Review

2022

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Growth factors (GFs) have a role in tissue repair and in the modulation of the expression of inflammatory cells in damage caused by pathogens. This study aims to systematize the evidence on the role of GFs in the pathogenesis of dengue. This scoping review considered all published peer-reviewed studies in the MEDLINE and Embase databases. Ultimately, 58 studies that analyzed GFs in dengue patients, published between 1998 and 2021, were included. DENV-2 infection and secondary infection were more frequent in the patients studied. ELISA and multiplex immunoassay (Luminex) were the most used measurement techniques. Increased levels of vascular endothelial growth factor, granulocyte–macrophage colony-stimulating factor, granulocyte colony-stimulating factor, transforming growth factor beta, and hepatocyte growth factor as well as reduced levels of platelet-derived growth factor and epidermal growth factor were observed in severe dengue in most studies. Vascular endothelial growth factor and hepatocyte growth factor were identified as biomarkers of severity. In addition, there is evidence that the dengue virus can use the growth factor pathway to facilitate its entry into the cell and promote its viral replication. The use of tyrosine kinase inhibitors is an alternative treatment for dengue that is being studied.

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“…1A and Table 1 ). Interestingly, some viruses encode growth factors that are homologous to those produced by the cells, allowing for the modulation of the RTK pathway (reviewed in references 12 and 13 ). One excellent example is the virus growth factor (VGF), the viral homolog of cellular epidermal growth factor (EGF), which is encoded by vaccinia virus (VACV), a prototypical poxvirus ( 14 , 15 ).…”

Section: Growth Factor Receptor Signalingmentioning

confidence: 99%