Bansode, Y.D. and Chattopadhyay, D. and Saha, B. (2019) Innate immune response in astrocytesinfected with herpes simplex virus 1. Archives of Virology , 164. pp. 1433-1439.

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Abstract

Herpes simplex virus 1 (HSV-1), a double-stranded DNA virus, infects epithelial surfaces and establishes latency in the central nervous system, where astrocytes are a major immune cell type. Here, we report changes that occur in the expression of pathogen recognition receptors, such as Toll-like receptors, DNA and RNA sensors, interferons, and interferon-stimulated genes, when astrocytes are infected with HSV-1 strain F. We observed upregulation of Toll-like receptors 2, 6 and 9, MDA5, and DAI along with an increase in the expression of type I interferons and interferon-stimulated genes such as IFIT1, IFIT3 and RNase L. These genes encode proteins that mediate the antiviral immune response. Herpes simplex virus 1 (HSV-1) infects cells at epithelial surfaces and subsequently migrates to the central nervous system (CNS), establishing a latent infection there in astrocytes, which are major innate immune cells of the CNS [1, 8, 10]. By forming glia limitans around blood capillaries, these cells are involved in the formation of the blood-brain barrier (BBB) [23] that limits the entry of larger molecules, pathogens, and infected cells into CNS parenchyma. Astrocytes are also involved in the maintenance of ion homeostasis in the CNS and monitoring synapses, which might be involved in recognition of intraneuronal transfer of viruses such as HSV. Astrocytes play important roles in glial scar formation in neuronal injury during trauma or infection [12] and in the innate immune response to invading virus, bacteria and parasites [11, 12, 14, 23]. In this study, we examined expression of innate immune receptors and the interferon response by astrocytes to HSV-1 infection in vitro. Innate immune responses of astrocytes are triggered following the recognition of pathogen-associated molecular patterns (PAMPs) by host-cell-expressed pathogen recognition receptors (PRRs), including Toll-like receptors (TLR) and cytoplasmic DNA and RNA sensors [12, 14, 19], which recognize viral PAMPs such as glycoproteins, unmethylated DNA, ssRNA and dsRNA. PRRs activate downstream signaling after sensing a specific PAMP, resulting in the induction of expression of various cytokines and interferons (IFNs). These IFNs then induce the expression of interferon-stimulated genes (ISGs), which have direct or indirect antiviral effector functions, resulting in inhibition of viral replication and elimination or containment of the infection. In order to identify molecules that could be involved in the anti-HSV immune response, we infected the mouse astrocyte cell line DBT with the HSV-1 strain F (HSV-1F) for different periods of time followed by reverse transcription real-time PCR using gene-specific primers (Table 1) or Western blots, as indicated.

Item Type:	Article
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	20 Feb 2020 08:42
Last Modified:	20 Feb 2020 08:42
URI:	http://nccs.sciencecentral.in/id/eprint/711

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