Interplay between Alpha/Beta and Gamma Interferons with B, T, and Natural Killer Cells in the Defense against Herpes Simplex Virus Type 1

Vollstedt, Sabine; Arnold, S.; Schwerdel, Cornelia; Franchini, Marco; Alber, Gottfried; Santo, James P. Di; Ackermann, Mathias; Suter, Mark

doi:10.1128/jvi.78.8.3846-3850.2004

Cited by 75 publications

(74 citation statements)

References 47 publications

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“…The lethal dose (LD)50 of untreated, neonatal C57BL/6 mice is 10 3 PFU of HSV-1 [4]. This was increased tenfold to 10 4 PFU of HSV-1 after rIFN-a treatment ( Fig. 1) and as previously shown [4].…”

Section: Resultssupporting

confidence: 61%

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The long‐term but not the short‐term antiviral effectof IFN‐α depends on Flt3 ligand and pDC

Vollstedt¹,

O’Keeffe²,

Ryf³

et al. 2006

Eur J Immunol

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The cooperation between IFN-a/b and FL, the ligand of Fms-like tyrosine kinase 3 (Flt3), plays an important role in the defense against herpes simplex virus type 1 (HSV-1) in neonates. Treatment of neonatal mice with recombinant IFN-a has a shortterm, FL-independent and a long-term, FL-dependent protective effect against HSV-1. In mice lacking FL, neonatal resistance against HSV-1 is very low and DC numbers in the spleen are reduced. The treatment of these mice with rIFN-a at day 6 resulted in an increased resistance against infection with HSV-1 at day 7. In C57BL/6 mice, treatment with rIFN-a at birth induced both FL and plasmacytoid DC (pDC), resulting in enhanced resistance against HSV-1 at day 7. In contrast, in mice lacking FL, IFN-a treatment at birth did not influence the splenic cell composition and had no effect on viral protection. The transfer of pDC to mice lacking FL enhanced viral resistance. Therefore, the induction and function of pDC, normally controlled by IFN-a/b and FL, are decisive for viral resistance in neonatal mice.

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Section: Resultssupporting

confidence: 61%

“…It is clear from studies using mice lacking type I IFN receptors that type I IFN plays a central role in the protective immune response [9,10]. IFN-a/b is immediately induced after viral attachment, recognition by Toll-like receptors, or after infection and replication in cells [11,12].…”

Section: Introductionmentioning

confidence: 99%

The long‐term but not the short‐term antiviral effectof IFN‐α depends on Flt3 ligand and pDC

Vollstedt¹,

O’Keeffe²,

Ryf³

et al. 2006

Eur J Immunol

Self Cite

View full text Add to dashboard Cite

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“…These results argue that inhibition of the type I IFN response by the 3C protein may be involved in EV71 pathogenesis. Type I IFN plays a crucial role in different aspects of immunity, including DC maturation, T-cell activation, and inhibition of viral replication (15,22,25,49). Therefore, it is reasonable to predict that when expressed during EV71 infection, the 3C protein may modulate not only innate immunity but also adaptive immunity.…”

Section: Discussionmentioning

confidence: 99%

The 3C Protein of Enterovirus 71 Inhibits Retinoid Acid-Inducible Gene I-Mediated Interferon Regulatory Factor 3 Activation and Type I Interferon Responses

Lei

Liu

et al. 2010

J Virol

187

225

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Enterovirus 71 (EV71) is a human pathogen that induces hand, foot, and mouth disease and fatal neurological diseases. Immature or impaired immunity is thought to associate with increased morbidity and mortality. In a murine model, EV71 does not facilitate the production of type I interferon (IFN) that plays a critical role in the first-line defense against viral infection. Administration of a neutralizing antibody to IFN-␣/␤ exacerbates the virus-induced disease. However, the molecular events governing this process remain elusive. Here, we report that EV71 suppresses the induction of antiviral immunity by targeting the cytosolic receptor retinoid acid-inducible gene I (RIG-I). In infected cells, EV71 inhibits the expression of IFN-␤, IFN-stimulated gene 54 (ISG54), ISG56, and tumor necrosis factor alpha. Among structural and nonstructural proteins encoded by EV71, the 3C protein is capable of inhibiting IFN-␤ activation by virus and RIG-I. Nevertheless, EV71 3C exhibits no inhibitory activity on MDA5. Remarkably, when expressed in mammalian cells, EV71 3C associates with RIG-I via the caspase recruitment domain. This precludes the recruitment of an adaptor IPS-1 by RIG-I and subsequent nuclear translocation of interferon regulatory factor 3. An R84Q or V154S substitution in the RNA binding motifs has no effect. An H40D substitution is detrimental, but the protease activity associated with 3C is dispensable. Together, these results suggest that inhibition of RIG-I-mediated type I IFN responses by the 3C protein may contribute to the pathogenesis of EV71 infection.

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“…Human and murine studies suggest that the innate immune response, specifically the ability to produce elevated levels of type I interferon (IFN) at early time points, provides a threshold of resistance to acute HSV-1 infection (44). Although the precise mechanisms by which type I IFNs function during HSV-1 infection are not fully understood in humans, murine studies have shown IFN-␣/␤ to inhibit the onset of immediateearly gene expression (2,22), limit viral spread into the nervous system (13), and activate host defenses such as NK cells (19).…”

mentioning

confidence: 99%

In Vivo Ablation of CD11c-Positive Dendritic Cells Increases Susceptibility to Herpes Simplex Virus Type 1 Infection and Diminishes NK and T-Cell Responses

Kassim

Rajasagi

Zhao

et al. 2006

J Virol

106

110

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The precise role of each of the seven individual CD11c؉ dendritic cell subsets (DCs) identified to date in the response to viral infections is not known. DCs serve as critical links between the innate and adaptive immune responses against many pathogens, including herpes simplex virus type 1 (HSV-1). The role of DCs as mediators of resistance to HSV-1 infection was investigated using CD11c-diphtheria toxin (DT) receptor-green fluorescent protein transgenic mice, in which DCs can be transiently depleted in vivo by treatment with low doses of DT. We show that ablation of DCs led to enhanced susceptibility to HSV-1 infection in the highly resistant C57BL/6 mouse strain. Specifically, we showed that the depletion of DCs led to increased viral spread into the nervous system, resulting in an increased rate of morbidity and mortality. Furthermore, we showed that ablation of DCs impaired the optimal activation of NK cells and CD4؉ and CD8 ؉ T cells in response to HSV-1. These data demonstrated that DCs were essential not only in the optimal activation of the acquired T-cell response to HSV-1 but also that DCs were crucial for innate resistance to HSV-1 infection.Based on serological evidence, it is estimated that 60 to 80% of the adult population is infected with herpes simplex virus type 1 (HSV-1) (46). Most infected individuals remain asymptomatic. Of symptomatic individuals, clinical presentation ranges from mild illness, such as the development of orofacial vesicular lesions, all the way to life-threatening systemic complications, such as hepatitis and encephalitis (39). The outcome of infection is known to be influenced by both specific and nonspecific genetically linked host defense mechanisms (32). The immune system is particularly important in controlling HSV-1 infection in both the periphery and the nervous system, although the events that initiate this immunity in humans are not very well understood. Underlying immunosuppression does not appear to explain the distinct outcomes of host-virus interaction. Rather, the observed range in clinical outcomes appears to reflect differences in intrinsic resistance to infection.Studies using inbred strains of mice have revealed critical insights into the immunological basis for resistance to . Specifically, a range in innate resistance to systemic, lethal HSV-1 infection exists and has subsequently led to the grouping of inbred mice into resistant, moderately susceptible, and susceptible categories based upon the levels of virus required to cause death. In all cases examined, mice of the C57 background (C57BL/6 and C57BL/10) are most resistant and best able to effectively control HSV-1 infection (35).Human and murine studies suggest that the innate immune response, specifically the ability to produce elevated levels of type I interferon (IFN) at early time points, provides a threshold of resistance to acute HSV-1 infection (44).

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Interplay between Alpha/Beta and Gamma Interferons with B, T, and Natural Killer Cells in the Defense against Herpes Simplex Virus Type 1

Cited by 75 publications

References 47 publications

The long‐term but not the short‐term antiviral effectof IFN‐α depends on Flt3 ligand and pDC

The long‐term but not the short‐term antiviral effectof IFN‐α depends on Flt3 ligand and pDC

The 3C Protein of Enterovirus 71 Inhibits Retinoid Acid-Inducible Gene I-Mediated Interferon Regulatory Factor 3 Activation and Type I Interferon Responses

In Vivo Ablation of CD11c-Positive Dendritic Cells Increases Susceptibility to Herpes Simplex Virus Type 1 Infection and Diminishes NK and T-Cell Responses

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