Innate and Adaptive Immune Responses to Herpes Simplex Virus

Chew, Tracy; Taylor, Kathryne E.; Mossman, Karen

doi:10.3390/v1030979

Cited by 115 publications

(119 citation statements)

References 178 publications

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“…iii) In principle, STING is a component of the host innate defenses against exogenous DNA, and its function has been linked to activation of IRF3 and NF-κB (13)(14)(15). Numerous studies have shown that wild-type HSV-1 is fully competent in blocking the activation of IRF3 and NF-κB (10,25,26). Nevertheless, it came as a surprise that wild-type HSV-1 replicated better in HEL cells that had been depleted of STING.…”

Section: Discussionmentioning

confidence: 99%

HSV-1 degrades, stabilizes, requires, or is stung by STING depending on ICP0, the US3 protein kinase, and cell derivation

Kalamvoki

Roizman

2014

Proc. Natl. Acad. Sci. U.S.A.

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STING (stimulator of IFN genes) activates the IFN pathway in response to cytosolic DNA. Knockout of STING in mice was reported to exacerbate the pathogenicity of herpes simplex virus 1 (HSV-1). Here we report the following: (i) STING is stable in cancer-derived HEp-2 or HeLa cells infected with wild-type HSV-1 but is degraded in cells infected with mutants lacking the genes encoding functional infected cell protein 0 (ICP0), ICP4, or the US3 protein kinase (US3-PK). In HEp-2 cells, depletion of STING by shRNA results in a decrease in the yields of wild-type or ΔICP0 viruses. (ii) STING is stable throughout infection with either wild-type or ICP0 mutant viruses in human embryonic lung cells (HEL) or HEK293T cells derived from normal tissues. In these cells, depletion of STING results in higher yields of both wild-type and ΔICP0 viruses. (iii) The US3-PK is also required for stabilization of IFI16, a nuclear DNA sensor. However, the stability of IFI16 does not correlate positively or negatively with that of STING. IFI16 is stable in STING-depleted HEL cells infected with wild-type virus. In contrast to HEL cells, IFI16 was undetectable in STING-depleted HEp-2 cells, and hence the role of HSV-1 in maintaining IFI16 could not be ascertained. The results indicate that in HSV-1-infected cells the stability of IFI16 and the function and stability of STING are dependent on cell derivation, the functional integrity of ICP0, and US3-PK, an indication that in wild-type virus-infected cells both proteins are actively stabilized. In HEp-2 cells, the stability of IFI16 requires STING.innate immunity | cell transformation T he studies described in this report stem from two observations. First, a voluminous literature singles out the infected cell protein 0 (ICP0) as the major herpes simplex virus 1 (HSV-1) protein dedicated to defeating host responses to infection (1). Many of the functions of ICP0 designed to defeat host responses are executed by direct interaction between ICP0 and host proteins (2-8). In some instances, a plausible connection is apparent but no physical contact between ICP0 and the host effector protein is demonstrable (9, 10). Thus, ICP0 is associated with blocking the activation of IRF3 although a physical interaction between ICP0 and IRF3 has not been reported (10). One hypothesis that could explain such observations is that ICP0 interacts with the partners of the targeted protein rather than the target itself.Second, ICP0 accumulates during the first phase of the replicative cycle in the nucleus in which it performs multiple functions to enable efficient replication. Sometime between 5 and 9 h after exposure of cells to virus and depending on cell line, functional integrity of ICP0, and the amount of foreign DNA introduced into the cell, etc., ICP0 disappears from the nucleus and accumulates in the cytoplasm (11, 12). Several functions of ICP0 linked to physical interactions with cytoplasmic proteins have been described. Thus, ICP0 interacts with EF-1δ and enhances translation efficiency and with CIN85 t...

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Section: Discussionmentioning

confidence: 99%

HSV-1 degrades, stabilizes, requires, or is stung by STING depending on ICP0, the US3 protein kinase, and cell derivation

Kalamvoki

Roizman

2014

Proc. Natl. Acad. Sci. U.S.A.

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“…To investigate how commensal microbiota support immune protection against HSV-2 infection in the vaginal mucosa, we first explored the effect of commensal bacteria on the innate immune response. Innate immunity plays a pivotal role in limiting viral replication and initiating adaptive immunity in response to primary viral infection (16,17). Following vaginal mucosal HSV-2 infection, production of proinflammatory cytokines, such as IL-6, TNF-α, and IL-12p40, was not impaired in antibiotic-treated mice (Fig.…”

Section: Antibiotic Treatment Induces An Imbalance In Microbial Compomentioning

confidence: 97%

Dysbiosis-induced IL-33 contributes to impaired antiviral immunity in the genital mucosa

Kim

Chang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Commensal microbiota are well known to play an important role in antiviral immunity by providing immune inductive signals; however, the consequence of dysbiosis on antiviral immunity remains unclear. We demonstrate that dysbiosis caused by oral antibiotic treatment directly impairs antiviral immunity following viral infection of the vaginal mucosa. Antibiotic-treated mice succumbed to mucosal herpes simplex virus type 2 infection more rapidly than water-fed mice, and also showed delayed viral clearance at the site of infection. However, innate immune responses, including type I IFN and proinflammatory cytokine production at infection sites, as well as induction of virusspecific CD4 and CD8 T-cell responses in draining lymph nodes, were not impaired in antibiotic-treated mice. By screening the factors controlling antiviral immunity, we found that IL-33, an alarmin released in response to tissue damage, was secreted from vaginal epithelium after the depletion of commensal microbiota. This cytokine suppresses local antiviral immunity by blocking the migration of effector T cells to the vaginal tissue, thereby inhibiting the production of IFN-γ, a critical cytokine for antiviral defense, at local infection sites. These findings provide insight into the mechanisms of homeostasis maintained by commensal bacteria, and reveal a deleterious consequence of dysbiosis in antiviral immune defense.commensal microbiota | dysbiosis | IL-33 | herpes simplex virus type 2 | genital tract

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“…The T H 1 cells preferentially develop during infections by intracellular microorganisms, such as occurs in viral infections (Chew et al, 2009). It is generally accepted that T H 1 cells mainly produce IFNg and are responsible for propagating cell-mediated immunity (Wang & Fish, 2012).…”

Section: Discussionmentioning

confidence: 99%

Hyperthyroid state orin vitrothyroxine treatment modulates T_H1/T_H2 responses during exposure to HSV-1 antigens

Varedi¹,

Shiri²,

Moattari³

et al. 2013

Journal of Immunotoxicology

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Increasingly in recent years, thyroid hormones (THs) have been considered to be important regulators of the immune system. However, their roles in host defense against viral infections are not clearly established. Therefore, this study was undertaken to examine proliferative activity and cytokine production by lymphocytes isolated from hyperthyroid and euthyroid Balb/c mice in response to herpes simplex virus-1 (HSV-1). Lymphocytes of hyperthyroid animals showed a significantly higher rate of proliferation and interferon (IFN)-g production when compared with that by lymphocytes from euthyroid mice. In vitro thyroxine (T4) treatment was similarly effective in the potentiation of proliferation, but not IFNg production, by euthyroid lymphocytes. Furthermore, the hyperthyroid state significantly attenuated ConA-, but not HSV-1-, induced interleukin (IL)-10 release; in vitro T4 treatment synergized this effect. These findings suggest that supra-physiologic TH levels (i.e. as occur in hyper-thyroid states) or in vitro TH treatment modulate T-helper (T H )1/T H 2 lymphocyte responses and thereby amplifies host defenses against viral infections. One may also conclude that THs may have a potential application in viral immunization and/or treatment of viral infections.

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Innate and Adaptive Immune Responses to Herpes Simplex Virus

Cited by 115 publications

References 178 publications

HSV-1 degrades, stabilizes, requires, or is stung by STING depending on ICP0, the US3 protein kinase, and cell derivation

HSV-1 degrades, stabilizes, requires, or is stung by STING depending on ICP0, the US3 protein kinase, and cell derivation

Dysbiosis-induced IL-33 contributes to impaired antiviral immunity in the genital mucosa

Hyperthyroid state orin vitrothyroxine treatment modulates T_H1/T_H2 responses during exposure to HSV-1 antigens

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Innate and Adaptive Immune Responses to Herpes Simplex Virus

Cited by 115 publications

References 178 publications

HSV-1 degrades, stabilizes, requires, or is stung by STING depending on ICP0, the US3 protein kinase, and cell derivation

HSV-1 degrades, stabilizes, requires, or is stung by STING depending on ICP0, the US3 protein kinase, and cell derivation

Dysbiosis-induced IL-33 contributes to impaired antiviral immunity in the genital mucosa

Hyperthyroid state orin vitrothyroxine treatment modulates TH1/TH2 responses during exposure to HSV-1 antigens

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Hyperthyroid state orin vitrothyroxine treatment modulates T_H1/T_H2 responses during exposure to HSV-1 antigens