Immune cell infiltration and persistence in the mouse trigeminal ganglion after infection of the cornea with herpes simplex virus type 1

Shimeld, C.; Whiteland, Joanne L.; Nicholls, Susan M.; Grinfeld, Esther; Easty, D L; Gao, Hong; Hill, Terry

doi:10.1016/0165-5728(95)00068-d

Cited by 127 publications

(92 citation statements)

References 29 publications

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“…4 Spread of the virus to the nervous system is accompanied by infiltration of CD8T cells that persist for long time after the resolution of acute infection. 5 In immunocompetent mice, this correlates with rapid termination of virus replication with little evidence of neuronal destruction, while in animals lacking CD8T cells virus clearance is delayed and accompanied by a striking loss of neurons. 4 Treatment of explants of trigeminal ganglia from infected mice with anti-CD8 antibodies causes accelerated reappearance of reactivating virus, 6 suggesting that CD8T cells may be capable of controlling virus replication without damaging the infected cells.…”

Section: Introductionmentioning

confidence: 99%

The herpes simplex virus-1 Us3 protein kinase blocks CD8T cell lysis by preventing the cleavage of Bid by granzyme B

et al. 2003

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The Us3 kinase is part of the antiapoptotic arsenal that salvages herpes simplex virus (HSV)-1-infected cells from damage caused by different stimuli. We demonstrate that Us3 protects HSV-1-infected cells from lysis by MHC class Irestricted CD8T cells without affecting antigen presentation. Expression of Us3 was associated with inhibition of caspase activation and reduced cleavage of the proapoptotic protein Bid. Recombinant granzyme B (GrB) failed to cleave Bid in cytosolic extracts from Us3 positive cells, while recombinant Bid served as substrate for Us3 phosphorylation, suggesting that modification of Bid by Us3 blocks its processing by GrB. Our data illustrate a new strategy of viral escape, where modification of a cellular proapoptotic substrate may prevent lysis of the infected cells without affecting other T-cell functions.

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Section: Introductionmentioning

confidence: 99%

The herpes simplex virus-1 Us3 protein kinase blocks CD8T cell lysis by preventing the cleavage of Bid by granzyme B

et al. 2003

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“…Accumulation of T cells, particularly CD8 ϩ T cells, was delayed and occurred coincident with the clearance of HSV-1 antigen from the ganglion. We and others previously reported the unexpected observation that the inflammatory response persisted well into latency, with associated production of IFN-␥ and TNF in close juxtaposition with infected neurons (11,27,41,59). In one study, TNF was the major cytokine produced in the ganglion and the only cytokine detected on the CNS side of the dorsal root entry zone (60).…”

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confidence: 99%

“…In contrast to what occurs in the cornea, macrophages rather than neutrophils dominate the early (day 3) inflammatory infiltrate in the trigeminal ganglion (Tg) after corneal inoculation of HSV (35,59). Macrophages were shown to be the primary producers of TNF, interleukin-12, and inducible nitric oxide synthase, whereas ␥␦ T cells produced IFN-␥ in the ganglion, and both cell types were found in close proximity to infected neurons, suggesting a role in the control of HSV-1 replication (35).…”

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confidence: 99%

Tumor Necrosis Factor (TNF) Protects Resistant C57BL/6 Mice against Herpes Simplex Virus-Induced Encephalitis Independently of Signaling via TNF Receptor 1 or 2

Lundberg¹,

Welander²,

Edwards

et al. 2007

J Virol

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Tumor necrosis factor (TNF) is a multifunctional cytokine that has a role in induction and regulation of host innate and adaptive immune responses. The importance of TNF antiviral mechanisms is reflected by the diverse strategies adopted by different viruses, particularly members of the herpesvirus family, to block TNF responses. TNF binds and signals through two receptors, Tnfrsf1a (TNF receptor 1 [TNFR1], or p55) and Tnfrsf1b (TNFR2, or p75). We report here that herpes simplex virus 1 (HSV-1) infection of TNF ؊/؊ mice on the resistant C57BL/6 genetic background results in significantly increased susceptibility (P < 0.0001, log rank test) to fatal HSV encephalitis (HSE) and prolonged persistence of elevated levels of virus in neural tissues. In contrast, although virus titers in neural tissues of p55 ؊/؊ N13 mice were elevated to levels comparable to what was found for the TNF ؊/؊ mice, the p55 ؊/؊ N13 mice were as resistant as control C57BL/6 mice (P > 0.05). The incidence of fatal HSE was significantly increased by in vivo neutralization of TNF using soluble TNFR1 (sTNFR1) or depletion of macrophages in C57BL/6 mice (P ‫؍‬ 0.0038 and P ‫؍‬ 0.0071, respectively). Strikingly, in vivo neutralization of TNF in HSV-1-infected p55 ؊/؊ p75 ؊/؊ mice by use of three independent approaches (treatment with soluble p55 receptor, anti-TNF monoclonal antibody, or in vivo small interfering RNA against TNF) resulted in significantly increased mortality rates (P ‫؍‬ 0.005), comparable in magnitude to those for C57BL/6 mice treated with sTNFR1 (P ‫؍‬ 0.0018). Overall, these results indicate that while TNF is required for resistance to fatal HSE, both p55 and p75 receptors are dispensable. Precisely how TNF mediates protection against HSV-1 mortality in p55 ؊/؊ p75 ؊/؊ mice remains to be determined.Early innate and subsequent adaptive immune responses to viral and bacterial pathogens are critically dependent on the tumor necrosis factor (TNF) superfamily of cytokines. These TNF superfamily cytokines act as effectors of host defense and regulate peripheral lymphoid tissue organogenesis and differentiation of natural killer cells and lymphoid cells (42,46). TNF, a multifunctional cytokine produced primarily by activated macrophages (70), functions as a key regulator of leukocyte trafficking by affecting chemokine expression and stimulating antigen presentation, which it does by inducing dendritic cell maturation (26, 58). TNF exists in two forms, a precursor 26-kDa membrane-bound form (mTNF) and a 17-kDa soluble form (sTNF), both of which are bioactive (46, 71). TNF and the closely related ligand lymphotoxin-␣ (LT) bind as homotrimers to two receptors, TNF receptor 1 (TNFR1, or p55) and TNFR2 (p75), which are widely expressed on most cell types (71). Activation of p55 generally results in gene activation that leads to induction of inflammatory and cytotoxic responses, while activation of TNFR2 is associated with thymocyte proliferation and T-cell activation. In response to TNF binding, lipopolysaccharide (LPS) and several other s...

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“…In infected ganglia, these cells morphologically resemble infiltrating immune cells. Differing approaches have been taken to the controversial issue of identifying SCs, including morphology and perineural position (Cecchini et al, 1999;Lu & Richardson, 1991;Shimeld et al, 1995), staining for SC marker GFAP and lack of staining for macrophage marker ED2 (Zhou et al, 1999), and S100 staining (Bradley et al, 1997). Confirmation of SC identity is hampered by the reported lack of expression of the SC-specific markers GFAP and S100 during SC proliferation (Wen et al, 1994).…”

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confidence: 99%

Herpes simplex virus infection of murine sensory ganglia induces proliferation of neuronal satellite cells

Elson

Speck

Simmons³

2003

Journal of General Virology

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Herpes simplex virus (HSV) is a virtually ubiquitous human pathogen that, following cutaneous infection, latently infects neurons of sensory ganglia. Satellite cells (SCs) ensheath and provide metabolic support for these neurons, and could potentially participate in controlling HSV disease. Although SCs are restrictive for HSV replication, hypercellularity of non-neuronal cells in ganglia is prominent during HSV infection in animal models. SCs proliferate in response to trauma, e.g. nerve cut or crush, but it is not known if proliferation occurs in response to viral infection. To address this issue, cell proliferation, measured by bromodeoxyuridine (BrdU) uptake, and immune infiltrate, measured by CD45 labelling, were examined during acute infection in a mouse model. Because SCs do not express CD45, the BrdU + CD45 2 cell subset represents the proliferating SC population. We report that during acute ganglionic HSV infection there is a substantial increase in SC numbers. We suggest that SC proliferation in response to HSV infection may occur in order to facilitate neuronal survival.Satellite cells (SCs) in the peripheral nervous system (PNS) physically and metabolically support neurons. Unlike neurons, SCs maintain the ability to divide in adult life, although these cells do not typically display evidence of rapid turnover. Consistent with this are findings of rare mitotic SCs and a small proportion of SCs labelled with tritiated thymidine present in ganglia of adult rodents and cats (Lieberman, 1976;Pannese, 1960;Wen et al., 1994). SCs proliferate in response to severe trauma, e.g. axotomy and nerve crush (Nathaniel & Nathaniel, 1973;Shinder et al., 1999), and proliferate in explant culture, in which ganglia are excised and cultured in vitro, eliminating invading blood cells while preserving structure (Wen et al., 1994). SCs proliferate in response to malnutrition, e.g. in vitamin E-deficient rats (Cecchini et al., 1999). It is proposed that proliferation of SCs in response to trauma facilitates neuronal recovery (Wen et al., 1994).The role of SCs in response to PNS infection by viruses, such as herpes simplex virus (HSV), is poorly characterized. During cutaneous infection HSV enters nerves and travels to sensory ganglia, where, after a brief bout of productive infection, it establishes latency in neurons. Neurons and SCs appear privileged in their response to HSV. In neurons this is reflected in an unusual ability to survive infection despite viral gene expression (Simmons & Tscharke, 1992), which in other cell types is typically associated with cell destruction (Roizman & Knipe, 2001). SCs undergo abortive infection with HSV, as shown by electron microscopy which finds only unenveloped virions in SCs (Hill et al., 1972) or no virions at all (Dillard et al., 1972). Viral antigens are rarely, if ever, found in SCs during acute ganglionic infection (Speck & Simmons, 1998). These studies suggest that efficient infection of SCs by HSV does not occur. Consistent with this are results of studies on infection of Sat....

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Immune cell infiltration and persistence in the mouse trigeminal ganglion after infection of the cornea with herpes simplex virus type 1

Cited by 127 publications

References 29 publications

The herpes simplex virus-1 Us3 protein kinase blocks CD8T cell lysis by preventing the cleavage of Bid by granzyme B

The herpes simplex virus-1 Us3 protein kinase blocks CD8T cell lysis by preventing the cleavage of Bid by granzyme B

Tumor Necrosis Factor (TNF) Protects Resistant C57BL/6 Mice against Herpes Simplex Virus-Induced Encephalitis Independently of Signaling via TNF Receptor 1 or 2

Herpes simplex virus infection of murine sensory ganglia induces proliferation of neuronal satellite cells

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