Cytokine production in the nervous system of mice during acute and latent infection with herpes simplex virus type 1.

Shimeld, C.; Whiteland, Joanne L.; Williams, Neil; Easty, D L; Hill, Terry

doi:10.1099/0022-1317-78-12-3317

Cited by 101 publications

(76 citation statements)

References 39 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2). These data and other reports of early induction of TNF expression in tissues targeted by HSV-1 are consistent with a protective role for TNF in HSV-1 infection (11,27,28,41,60). Additionally, intraperitoneal injection of TNF 4 h before or 8 h after intraperitoneal HSV-1 inoculation of C57BL/6 mice significantly extended their survival rate compared to that for untreated C57BL/6 mice (55).…”

Section: Discussionsupporting

confidence: 77%

“…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). These observations imply an important role for IFN-␥ and TNF in the control of HSV-1 infection in neurons during acute and latent infection.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionsupporting

confidence: 77%

mentioning

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

View full text Add to dashboard Cite

show abstract

“…The backbone virus R3659 infection ameliorated the [29][30][31] We will continue studies on the cytokine response to HSV vectors.…”

Section: Figure 5 the Hematoxylin-eosin Staining Of The Spinal Cords mentioning

confidence: 99%

Expression of interleukin-4 but not of interleukin-10 from a replicative herpes simplex virus type 1 viral vector precludes experimental allergic encephalomyelitis

et al. 2001

View full text Add to dashboard Cite

We have used interleukin (IL)-4 and -10-producing HSV-1 ␥ 1 34.5 deletion viruses in gene therapy of a BALB/c model of experimental allergic encephalomyelitis (EAE), a T cellmediated demyelinating disease of the central nervous system. It is known that in EAE of mice the Th2-type cytokines are down-regulated and the Th1-type cytokines up-regulated during the onset and relapse of the disease. Therefore, we tested two HSV-1 recombinants expressing the Th2-type cytokines IL-4 and IL-10. The recombinant viruses were injected intracranially (i.c.) in BALB/c mice 6 days after induction of EAE. As control groups we used mice without

show abstract

“…47 This suggests not only the nature of the gene product that can influence outcome, but also the nature of the vector and whether the cell is infected or transfected, possibly through the cytokines they coproduce. [69][70][71] There have been few cases in current EAE studies (Table 1) where the biological effect was directly attributed to the secretion of the transgene, 38,46,58 which makes it difficult to determine the real therapeutic potential of a particular gene product.…”

Section: Local Immunogene Therapy In Cns Autoimmunitymentioning

confidence: 99%

Gene therapy in autoimmune, demyelinating disease of the central nervous system

Baker

Hankey

2003

Gene Ther

View full text Add to dashboard Cite

Cytokine production in the nervous system of mice during acute and latent infection with herpes simplex virus type 1.

Cited by 101 publications

References 39 publications

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

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

Expression of interleukin-4 but not of interleukin-10 from a replicative herpes simplex virus type 1 viral vector precludes experimental allergic encephalomyelitis

Gene therapy in autoimmune, demyelinating disease of the central nervous system

Contact Info

Product

Resources

About