Modulation of sFas indicates apoptosis in human herpes simplex encephalitis

Sabri, Farideh; Granath, Fredrik; Hjalmarsson, Anders; Aurelius, Elisabeth; Sköldenberg, Birgit

doi:10.1016/j.jneuroim.2005.10.003

Cited by 20 publications

(12 citation statements)

References 37 publications

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“…Normal HSV infections are characterized by cycling between lytic infection at epithelial surfaces and stages of latency in neuronal cells (reviewed in reference 47). The pathology of HSV infection is greatly influenced by the immune status of the host, which impacts both disease severity and the frequency of reactivation (21,35,42,48,69).…”

Section: By Examining Dcs Generated From Mavs (Ips-1) Knockout (Ko) Mmentioning

confidence: 99%

The Virion Host Shutoff Protein of Herpes Simplex Virus 1 Blocks the Replication-Independent Activation of NF-κB in Dendritic Cells in the Absence of Type I Interferon Signaling

Cotter

Kim

Nguyen

et al. 2011

J Virol

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Immune evasion is a defining feature of the virus-host relationship. During infection, herpes simplex virus type 1 (HSV-1) utilizes multiple proteins to manipulate the host immune response. In the present study, we investigated the mechanism by which the virion host shutoff (vhs) protein blocks the activation of dendritic cells (DCs). Previously, we found that coinfection of wild-type HSV-1 with a panel of RNA viruses resulted in a block to DC activation that was attributable to vhs. These observations led us to hypothesize that the vhs-mediated inhibition was dependent on signaling through the RIG-I-like receptor (RLR) signaling pathway. By examining DCs generated from MAVS (IPS-1) knockout (KO) mice, we determined that RLR/MAVS signaling is not essential for the DC response to HSV-1. We also evaluated the requirement for the type I interferon ( Herpes simplex virus type 1 (HSV-1) is a highly successful human pathogen belonging to the Alphaherpesviridae subfamily of herpesviruses. Initial exposure to virus results in lifelong infection, and it is estimated that between 60 and 80% of humans are seropositive for the virus (52). Normal HSV infections are characterized by cycling between lytic infection at epithelial surfaces and stages of latency in neuronal cells (reviewed in reference 47). The pathology of HSV infection is greatly influenced by the immune status of the host, which impacts both disease severity and the frequency of reactivation (21,35,42,48,69).Early during primary infection of the epithelium, HSV encounters a specialized type of immune cell, the dendritic cells (DCs). DCs function as a crucial link between innate and adaptive immune responses (reviewed in reference 4). These cells survey peripheral tissues in an immature state and undergo a process referred to as maturation (or activation) upon encounter with virus-associated molecules (5, 32). DC maturation is initially characterized by the secretion of type I and III interferons (IFNs) and proinflammatory cytokines (e.g., interleukin 6 [IL-6], tumor necrosis factor alpha [TNF-␣], and IL-12) and regulation of molecules necessary for migration to peripheral lymph nodes (32). En route to these secondary lymphoid organs, the DCs upregulate several costimulatory markers (CD86 and CD80) and load viral antigen onto major histocompatibility complex (MHC) molecules, which in concert serve to stimulate naïve B and T cells (4).Numerous viral proteins are utilized by HSV to evade the host immune response at all stages of the virus life cycle (7,9,31,33,39,63). Immunomodulatory proteins are either produced during the virus replication cycle or prepackaged in viral particles in the tegument and deposited into the cell immediately following virus envelope-host cell membrane fusion. The virion-host shutoff (vhs) protein is one such tegument-localized viral protein synthesized with late kinetics and packaged into mature virion particles (14,25,51,59). Functionally, vhs is a viral RNase that is known to preferentially degrade both host and viral mRNA species (1...

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Section: By Examining Dcs Generated From Mavs (Ips-1) Knockout (Ko) Mmentioning

confidence: 99%

The Virion Host Shutoff Protein of Herpes Simplex Virus 1 Blocks the Replication-Independent Activation of NF-κB in Dendritic Cells in the Absence of Type I Interferon Signaling

Cotter

Kim

Nguyen

et al. 2011

J Virol

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“…These findings suggest that apoptosis reduces the severity of HSK during HSV infection. HDAP is not solely restricted to ocular HSV disease, as others have reported that apoptosis plays a role in herpetic brain disease (49,52). However, in this case apoptosis seems to be acting to facilitate brain disease progression.…”

mentioning

confidence: 93%

p53 and hTERT Determine Sensitivity to Viral Apoptosis

Nguyen

Kraft

Aubert

et al. 2007

J Virol

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Apoptosis is a potent host defense against microbes. Most viruses have adapted strategies to counteract this response. Herpes simplex virus (HSV) produces a balance between pro-and antiapoptotic processes during infection. When antiapoptotic signals become limiting, infected cells die through HSV-dependent apoptosis (HDAP). Oncogenic pathways were previously implicated in HDAP susceptibility. Here, we exploited our ability to selectively express all, one, or no oncogenes in the well-defined HeLa cell system to dissect the requirements for HDAP. Human papillomavirus E6 and E7 oncogene expression was inhibited by the E2 viral repressor. Sole expression of E6 mediated HDAP sensitization. Next, two known cellular targets of E6 were independently modulated. This demonstrated that E6 sensitizes HeLa cells to HDAP through hTERT and p53. Given the universality of the apoptotic antiviral response, p53 and telomerase regulation will likely be important for counteracting host defenses in many other viral infections.

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“…Bigger cohorts may be needed to determine whether concentrations are correlated with clinical outcome (Studahl et al 2000). Additional biomarker that might indicate the severity and progression of cerebral injury in HSE is soluble Fas (sFas) which is involved in apoptosis through the Fas/Fas Ligand pathway (Sabri et al 2006). Zipp et al 1998).…”

Section: Herpes Simplex Encephalitismentioning

confidence: 99%

Biomarkers of Encephalitis

Bonneh‐Barkay¹

2011

Pathogenesis of Encephalitis

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Modulation of sFas indicates apoptosis in human herpes simplex encephalitis

Cited by 20 publications

References 37 publications

The Virion Host Shutoff Protein of Herpes Simplex Virus 1 Blocks the Replication-Independent Activation of NF-κB in Dendritic Cells in the Absence of Type I Interferon Signaling

The Virion Host Shutoff Protein of Herpes Simplex Virus 1 Blocks the Replication-Independent Activation of NF-κB in Dendritic Cells in the Absence of Type I Interferon Signaling

p53 and hTERT Determine Sensitivity to Viral Apoptosis

Biomarkers of Encephalitis

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