An Anti-Inflammatory Role of VEGFR2/Src Kinase Inhibitor in Herpes Simplex Virus 1-Induced Immunopathology

Sharma, Shalini; Mulik, Sachin; Kumar, Naveen; Suryawanshi, Amol; Rouse, Barry T.

doi:10.1128/jvi.00034-11

Cited by 33 publications

(28 citation statements)

References 31 publications

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“…The eyes were examined on different time points post infection with a slit lamp biomicroscope (KOWA), and the clinical severity of keratitis and angiogenesis of individually scored mice was recorded. The scoring system was as described previously [12]. …”

Section: Methodsmentioning

confidence: 99%

Herpes virus entry mediator (HVEM) modulates proliferation and activation of regulatory T cells following HSV-1 infection

Sharma

Rajasagi

Veiga-Parga

et al. 2014

Microbes and Infection

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In many infections, especially those that are chronic such as Herpes Simplex Virus-1 (HSV-1), the outcome may be influenced by the activity of one or more types of regulatory T cells (Tregs). Some infections can cause Treg expansion, but how viruses might promote preferential Treg expansion is has been unclear. In this report, we demonstrate a possible mechanism by which HSV (Herpes Simplex virus-1) infection could act to signal and expands the Treg population. We show that CD4+ FoxP3+ Tregs up- regulate HVEM (herpes virus entry mediator), which is a binding site for major viral glycoprotein HSVgD, following HSV infection, which is a binding site for major viral glycoprotein HSVgD. Recombinant HSVgD enhanced the proliferation of CD4+ FoxP3+ Tregs cells in vitro. Furthermore, compared to wild type (WT), HVEM deficient mice (HVEM−/−) generated a weaker Treg responses represented by significantly diminished ratios of CD4+FoxP3+/CD4+FoxP3− cells along with diminished proportions of FoxP3+ Tregs cells co-expressing Treg activation markers and a reduced MFI of FoxP3 expression on CD4+ T cells. Consistent with defective Treg responses, HVEM−/− animals were more susceptible to HSV-1 induced ocular immunopathology, with more severe lesions in HVEM−/− animals. Our results indicate that HVEM regulates Treg responses, and its modulation could represent a useful approach to control HSV induced corneal immunopathology

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Section: Methodsmentioning

confidence: 99%

Herpes virus entry mediator (HVEM) modulates proliferation and activation of regulatory T cells following HSV-1 infection

Sharma

Rajasagi

Veiga-Parga

et al. 2014

Microbes and Infection

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“…The new vessels formed from the nearby limbus are not structurally sound, allowing for the extravasation of inflammatory mediators into the corneal stroma and ultimately leading to scarring and vision impairment. 13; 22; 68; 125 Thus, a prerequisite for corneal neovascularization seems to be an intact adaptive immune response that includes an appropriate degree of CD4 + T-cell infiltration into the cornea. 7 …”

Section: Hsv-1 Background and Corneal Infection Hsv-1 Cell Entrymentioning

confidence: 99%

Corneal lymphangiogenesis in herpetic stromal keratitis

Park

Chang

Garg

et al. 2015

Survey of Ophthalmology

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Corneal lymphangiogenesis is the extension of lymphatic vessels into the normally alymphatic cornea, a process that compromises the cornea’s immune privileged state and facilitates herpetic stromal keratitis (HSK). HSK results most commonly from infection by herpes simplex virus-1 (HSV-1) and is characterized by immune- and inflammation-mediated damage to the deep layers of the cornea. Current research demonstrates the potential of anti-lymphangiogenic therapy to decrease and prevent herpes-induced lymphangiogenesis.

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“…Curiously, avastin (and its more purified product lucensis) appears to be more effective to control aberrant angiogenesis in the human retina (wet macular degeneration) than it is against tumor angiogenesis in the cancers it was developed to control. Avastin works weakly against mouse CV (Sharma et al, 2011) (Table 1) (Fig. 6), but the more appropriate reagent that is specific to mouse VEGF has yet to be evaluated.…”

Section: Preventing and Controlling CVmentioning

confidence: 99%

“…One such approach is to counteract downstream signaling effects of receptor binding. SRC kinase inhibitor drugs achieve that objective (Sharma et al, 2011) (Table 1) (Fig. 6).…”

Section: Preventing and Controlling CVmentioning

confidence: 99%

Pathogenesis of herpes stromal keratitis – A focus on corneal neovascularization

Gimenez

Suryawanshi

Rouse

2013

Progress in Retinal and Eye Research

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The cornea is a complex sensory organ that must maintain its transparency for optimal vision. Infections such as with herpes simplex virus can result in blinding immunoinflammatory reactions referred to as herpes stromal keratitis (HSK). In this review we discuss the pathogenesis of HSK referring to work mainly done using animal model systems. We briefly discuss the role of multiple cell types and soluble mediators but focus on the critical role of corneal vascularization (CV) in contributing to corneal damage. We describe how VEGF and other angiogenic molecules are induced following infection and discuss the many ways by which CV can be controlled. Speculations are made regarding future approaches that could improve the management of HSK.

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An Anti-Inflammatory Role of VEGFR2/Src Kinase Inhibitor in Herpes Simplex Virus 1-Induced Immunopathology

Cited by 33 publications

References 31 publications

Herpes virus entry mediator (HVEM) modulates proliferation and activation of regulatory T cells following HSV-1 infection

Herpes virus entry mediator (HVEM) modulates proliferation and activation of regulatory T cells following HSV-1 infection

Corneal lymphangiogenesis in herpetic stromal keratitis

Pathogenesis of herpes stromal keratitis – A focus on corneal neovascularization

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