ICAM-5 modulates cytokine/chemokine production in the CNS during the course of herpes simplex virus type 1 infection

Tse, Margaret Chui Ling; Lane, Crystal; Mott, Kevin R.; Onlamoon, Nattawat; Hsiao, Hui Mien; Perng, Guey Chuen

doi:10.1016/j.jneuroim.2009.06.007

Cited by 16 publications

(12 citation statements)

References 32 publications

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“…The expression of some chemokines is upregulated upon HSV-1 and HSV-2 infection [42], [43] leading to leukocyte infiltration, which may be as pathogenic as viral infection [44]. In fact, chemokines are important in HSE pathogenesis in humans [11].…”

Section: Discussionmentioning

confidence: 99%

Enhancement of Chemokine Function as an Immunomodulatory Strategy Employed by Human Herpesviruses

et al. 2012

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Herpes simplex virus (HSV) types 1 and 2 are highly prevalent human neurotropic pathogens that cause a variety of diseases, including lethal encephalitis. The relationship between HSV and the host immune system is one of the main determinants of the infection outcome. Chemokines play relevant roles in antiviral response and immunopathology, but the modulation of chemokine function by HSV is not well understood. We have addressed the modulation of chemokine function mediated by HSV. By using surface plasmon resonance and crosslinking assays we show that secreted glycoprotein G (SgG) from both HSV-1 and HSV-2 binds chemokines with high affinity. Chemokine binding activity was also observed in the supernatant of HSV-2 infected cells and in the plasma membrane of cells infected with HSV-1 wild type but not with a gG deficient HSV-1 mutant. Cell-binding and competition experiments indicate that the interaction takes place through the glycosaminoglycan-binding domain of the chemokine. The functional relevance of the interaction was determined both in vitro, by performing transwell assays, time-lapse microscopy, and signal transduction experiments; and in vivo, using the air pouch model of inflammation. Interestingly, and in contrast to what has been observed for previously described viral chemokine binding proteins, HSV SgGs do not inhibit chemokine function. On the contrary, HSV SgGs enhance chemotaxis both in vitro and in vivo through increasing directionality, potency and receptor signaling. This is the first report, to our knowledge, of a viral chemokine binding protein from a human pathogen that increases chemokine function and points towards a previously undescribed strategy of immune modulation mediated by viruses.

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Section: Discussionmentioning

confidence: 99%

Enhancement of Chemokine Function as an Immunomodulatory Strategy Employed by Human Herpesviruses

et al. 2012

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“…Previous studies have shown that ICAM-5 may be an important signaling molecule for immune cell regulation during viral CNS infection; therefore, we also examined ICAM-5 expression at 6 days postinfection (dpi) i.m. with EV-D68 strain IL/14-18952 or mock-infected controls (34,35). ICAM-5 RNA expression was slightly higher in both infected and mock-infected mouse brains than in the P2 mouse brains; however, ICAM-5 RNA expression was still ϳ5-fold lower than that in the adult mouse cortex (Fig.…”

mentioning

confidence: 88%

Contemporary Circulating Enterovirus D68 Strains Infect and Undergo Retrograde Axonal Transport in Spinal Motor Neurons Independent of Sialic Acid

Hixon

Clarke²,

Tyler

2019

J Virol

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Enterovirus D68 (EV-D68) is an emerging virus that has been identified as a cause of recent outbreaks of acute flaccid myelitis (AFM), a poliomyelitis-like spinal cord syndrome that can result in permanent paralysis and disability. In experimental mouse models, EV-D68 spreads to, infects, and kills spinal motor neurons following infection by various routes of inoculation. The topography of virus-induced motor neuron loss correlates with the pattern of paralysis. The mechanism(s) by which EV-D68 spreads to target motor neurons remains unclear. We sought to determine the capacity of EV-D68 to spread by the neuronal route and to determine the role of known EV-D68 receptors, sialic acid and intracellular adhesion molecule 5 (ICAM-5), in neuronal infection. To do this, we utilized a microfluidic chamber culture system in which human induced pluripotent stem cell (iPSC) motor neuron cell bodies and axons can be compartmentalized for independent experimental manipulation. We found that EV-D68 can infect motor neurons via their distal axons and spread by retrograde axonal transport to the neuronal cell bodies. Virus was not released from the axons via anterograde axonal transport after infection of the cell bodies. Prototypic strains of EV-D68 depended on sialic acid for axonal infection and transport, while contemporary circulating strains isolated during the 2014 EV-D68 outbreak did not. The pattern of infection did not correspond with the ICAM-5 distribution and expression in either human tissue, the mouse model, or the iPSC motor neurons. IMPORTANCE Enterovirus D68 (EV-D68) infections are on the rise worldwide. Since 2014, the United States has experienced biennial spikes in EV-D68-associated acute flaccid myelitis (AFM) that have left hundreds of children paralyzed. Much remains to be learned about the pathogenesis of EV-D68 in the central nervous system (CNS). Herein we investigated the mechanisms of EV-D68 CNS invasion through neuronal pathways. A better understanding of EV-D68 infection in experimental models may allow for better prevention and treatment strategies of EV-D68 CNS disease.

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“…Crucially, the telencephalon region of the brain was found to have enhanced ICAM-5 expression, this receptor could help explain the neurotropism of this virus ( Wei et al, 2016 ; Messacar et al, 2018 ). Herpes Simplex Virus-1, another well-known neurotropic virus, also interacts with ICAM-5 to mediate cytokine secretion during infection ( Tse et al, 2009 ). Although these studies shed a light on how EV-D68 may achieve its neuro-invasive capability, many more questions remain concerning the factors which determine the variability in disease severity which is seen in clinical cases.…”

Section: Ev-d68 Association With Acute Flaccid Myelitis (Afm)mentioning

confidence: 99%

Enterovirus D68 – The New Polio?

et al. 2018

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Enterovirus D68 (EV-D68) has emerged over the recent years, with large outbreaks worldwide. Increased occurrence has coincided with improved clinical awareness and surveillance of non-polio enteroviruses. Studies showing its neurotropic nature and the change in pathogenicity have established EV-D68 as a probable cause of Acute Flaccid Myelitis (AFM). The EV-D68 storyline shows many similarities with poliovirus a century ago, stimulating discussion whether EV-D68 could be ascertaining itself as the “new polio.” Increasing awareness amongst clinicians, incorporating proper diagnostics and integrating EV-D68 into accessible surveillance systems in a way that promotes data sharing, will be essential to reveal the burden of disease. This will be a necessary step in preventing EV-D68 from becoming a threat to public health.

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ICAM-5 modulates cytokine/chemokine production in the CNS during the course of herpes simplex virus type 1 infection

Cited by 16 publications

References 32 publications

Enhancement of Chemokine Function as an Immunomodulatory Strategy Employed by Human Herpesviruses

Enhancement of Chemokine Function as an Immunomodulatory Strategy Employed by Human Herpesviruses

Contemporary Circulating Enterovirus D68 Strains Infect and Undergo Retrograde Axonal Transport in Spinal Motor Neurons Independent of Sialic Acid

Enterovirus D68 – The New Polio?

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