Herpes Simplex Virus 1 Infection Induces Activation and Subsequent Inhibition of the IFI16 and NLRP3 Inflammasomes
Autor: | Leela Chikoti, Karen E. Johnson, Bala Chandran |
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Rok vydání: | 2013 |
Předmět: |
Inflammasomes
Interleukin-1beta Immunology Down-Regulation Herpesvirus 1 Human Biology medicine.disease_cause Microbiology Immediate early protein Cell Line Proinflammatory cytokine AIM2 Virology NLR Family Pyrin Domain-Containing 3 Protein medicine Humans Secretion IFI16 Effector Nuclear Proteins Herpes Simplex Inflammasome Phosphoproteins Virus-Cell Interactions Cell biology Herpes simplex virus Insect Science Carrier Proteins medicine.drug |
Zdroj: | Journal of Virology. 87:5005-5018 |
ISSN: | 1098-5514 0022-538X |
Popis: | Inflammasomes are multiprotein complexes that recognize pathogens and pathogen- or danger-associated molecular patterns. They induce the maturation and secretion of powerful proinflammatory interleukin-1B (IL-1β), IL-18, and IL-33 cytokines, which in turn activate expression of other immune genes and lymphocyte recruitment to the site of primary infection, thereby controlling invading pathogens. Inflammasomes are comprised of cytoplasmic sensor molecules, such as NLRP3 and AIM2 or nuclear sensor IFI16, the adaptor protein ASC (apoptosis-associated speck-like protein containing CARD), and the effector protein procaspase-1. Herpes simplex virus 1 (HSV-1), a ubiquitous virus that infects humans and establishes life-long latency, has evolved numerous mechanisms to evade host detection and immune responses. Here, we show that early during in vitro infection of human foreskin fibroblasts (2 to 4 h), HSV-1 induced the activation of the IFI16 and NLRP3 inflammasomes and maturation of IL-1β. Independent of viral gene expression, IFI16 recognized the HSV-1 genome in infected cell nuclei, relocalized, and colocalized with ASC in the cytoplasm. However, HSV-1 specifically targeted IFI16 for rapid proteasomic degradation at later times postinfection, which was dependent on the expression of ICP0, an immediate early protein of HSV-1. In contrast, NLRP3, AIM2, and ASC levels were not decreased. Also, caspase-1 was “trapped” in actin clusters at later time points that likely blocked the NLRP3/IFI16 inflammasome activity. In addition, the secretion of mature IL-1β was inhibited. These results suggest that though the host cell responds to HSV-1 infection by IFI16 and NLRP3 inflammasomes early during infection, HSV-1 has evolved mechanisms to shut down these responses to evade the proinflammatory consequences. |
Databáze: | OpenAIRE |
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