Host Intrinsic and Innate Intracellular Immunity During Herpes Simplex Virus Type 1 (HSV-1) Infection

Alandijany, Thamir A.

doi:10.3389/fmicb.2019.02611

Cited by 40 publications

(38 citation statements)

References 215 publications

(348 reference statements)

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“…Detection of viral nucleic acid by host pattern recognition receptors (PRRs) plays a critical role in the activation of signalling cascades that lead to the production of pro-inflammatory cytokines, including type-I, II, and III IFNs ( Unterholzner and Almine, 2019 ; Stempel et al, 2019 ; Alandijany, 2019 ). Secretion of IFNs leads to the induction of hundreds of IFN stimulated genes (ISGs) that generate a cellular antiviral state that limits virus propagation and spread.…”

Section: Icp0 Scrambles Innate Immune Pathwaysmentioning

confidence: 99%

The HSV-1 ubiquitin ligase ICP0: Modifying the cellular proteome to promote infection

et al. 2020

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Highlights ICP0 is a viral E3 ubiquitin ligase that promotes HSV-1 infection. ICP0 interacts with multiple component proteins of the ubiquitin pathway. ICP0 disrupts multiple cellular processes activated in response to infection ICP0 remodels the SUMO proteome to counteract host immune defences to infection. ICP0 is an attractive drug target for the development of antiviral HSV-1 therapeutics.

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Section: Icp0 Scrambles Innate Immune Pathwaysmentioning

confidence: 99%

The HSV-1 ubiquitin ligase ICP0: Modifying the cellular proteome to promote infection

et al. 2020

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“…Interestingly, whilst DNA viruses typically initiate VRC formation at or in close proximity to PML NBs, many PML NB proteins contribute to the intrinsic antiviral restriction of DNA viruses if their function is not antagonized by the virus. These proteins include PML itself, the transcription corepressor and histone chaperone death domain associated protein 6 (DAXX), transcriptional regulator ATRX, transcription co-regulator Sp100, and E3 SUMO-protein ligase PIAS1 [3,24,[28][29][30][31][32][33][34]. This has led many to questions regarding whether the spatial relationship between VRCs and PML NBs is the result of viral strategies to target these nuclear domains or antiviral strategies that target viral genomes [3,6,24].…”

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confidence: 99%

“…ICP0 transiently localizes to PML NBs, mediating the proteasome-dependent degradation of PML and Sp100 and the disruption of PML NB through the E3 ubiquitin ligase activity of its really interesting new gene (RING) domain [37][38][39]. In the absence of ICP0, PML and other PML NB proteins act to suppress HSV-1 gene expression and restrict infection, highlighting the intrinsic antiviral function of PML NBs and the requirement of HSV-1 to antagonize this aspect of PML NB function [3,24,[27][28][29]31,40]. The necessity to antagonize the PML NB function appears to be shared by most if not all herpesviruses.…”

mentioning

confidence: 99%

“…For example, the varicella zoster virus (VZV) Orf61 protein disrupts PML NBs to antagonize sequestration of viral nucleocapsids within PML 'cages' [41,42]. Furthermore, members of the beta-herpesviruses such as cytomegalovirus (CMV) as well as members of the gamma-herpesviruses such as Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) also utilize immediate-early or early proteins that disrupt PML NB function, either through the disruption of PML NBs, or through the mislocalization or degradation of PML NB proteins [3,30,31,39].The interplay between PML NBs and initiation of VRCs is also relatively well characterized in the context of HAdV infection. Drawing parallels with herpesviruses, HAdV early proteins antagonize the repression of viral gene expression by PML NB proteins.…”

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confidence: 99%

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Replication Compartments of DNA Viruses in the Nucleus: Location, Location, Location

Charman

Weitzman

2020

Viruses

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DNA viruses that replicate in the nucleus encompass a range of ubiquitous and clinically important viruses, from acute pathogens to persistent tumor viruses. These viruses must co-opt nuclear processes for the benefit of the virus, whilst evading host processes that would otherwise attenuate viral replication. Accordingly, DNA viruses induce the formation of membraneless assemblies termed viral replication compartments (VRCs). These compartments facilitate the spatial organization of viral processes and regulate virus-host interactions. Here, we review advances in our understanding of VRCs. We cover their initiation and formation, their function as the sites of viral processes, and aspects of their composition and organization. In doing so, we highlight ongoing and emerging areas of research highly pertinent to our understanding of nuclear-replicating DNA viruses.Viruses 2020, 12, 151 2 of 20 The Initiation and Formation of Replication CompartmentsDNA viruses that replicate in the nucleus exhibit a diverse array of strategies to complete their replication cycle and ultimately produce progeny virions. Despite their many differences, the strategies employed by DNA viruses to initiate productive infection and establish VRCs share many features in common. Indeed, it is likely that all DNA viruses that replicate in the nucleus form VRCs. Following penetration of the host cell and the transport of viral capsids/cores, viral DNA genomes enter the nucleus, where they begin a program of temporally regulated gene expression that initiates productive infection [1,2]. Early gene products include viral proteins required to manipulate the host-cell environment and replicate the viral genome. Viral replication proteins interact with the viral genome and initiate genome replication leading to VRC formation, which is often in concert with certain co-opted host proteins. However, these viruses must overcome several challenges to form VRCs successfully. Firstly, incoming genomes must avoid cellular intrinsic antiviral defenses and homeostatic regulatory pathways such as elements of the DNA damage response (DDR) that respond to the presence of foreign DNA and act to suppress viral gene expression [3][4][5][6][7][8][9][10]. Secondly, VRCs typically form at specific sites within the nucleus, suggesting that viral genomes need to be targeted to these sites in order to initiate VRC formation [6,11,12]. Furthermore, it has been hypothesized that the formation and growth of VRCs may require manipulation of the nuclear environment and the re-organization of host chromatin to overcome the spatial restraints of the nucleus [11][12][13][14][15]. In this section, we review key features of VRC initiation and highlight some major challenges to VRC formation. Interplay between Viral Replication Compartment Formation and Promyelocytic Leukemia Protein Nuclear BodiesA common theme amongst many nuclear-replicating DNA viruses is initiation of VRCs at sites in close proximity to promyelocytic leukemia protein (PML) nuclear bodies (NBs). Since the dis...

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“…The HSV-1 tegument-associated proteins ICP0 and ICP4 are two key factors during HSV-1 replication. Both proteins are not only important modulators of intrinsic and innate immunity (Alandijany, 2019;Tognarelli et al, 2019), but are also crucial during the initiation of the viral gene expression cascade (Guo et al, 2010). On the one hand, it has been suggested that ICP4 might be an L-particle specific viral protein (Szilágyi and Cunningham, 1991;Heilingloh et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Mass Spectrometric Characterization of HSV-1 L-Particles From Human Dendritic Cells and BHK21 Cells and Analysis of Their Functional Role

et al. 2020

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Herpes simplex virus type 1 (HSV-1) is a very common human pathogenic virus among the world's population. The lytic replication cycle of HSV-1 is, amongst others, characterized by a tripartite viral gene expression cascade, the assembly of nucleocapsids involving their subsequent nuclear egress, tegumentation, reenvelopment and the final release of progeny viral particles. During productive infection of a multitude of different cell types, HSV-1 generates not only infectious heavy (H-) particles, but also non-infectious light (L-) particles, lacking the capsid. In monocytederived mature dendritic cells (mDCs), HSV-1 causes a non-productive infection with the predominant release of L-particles. Until now, the generation and function of L-particles is not well understood, however, they are described as factors transferring viral components to the cellular microenvironment. To obtain deeper insights into the L-particle composition, we performed a mass-spectrometry-based analysis of L-particles derived from HSV-1-infected mDCs or BHK21 cells and H-particles from the latter one. In total, we detected 63 viral proteins in both Hand L-particle preparations derived from HSV-1-infected BHK21 cells. In L-particles from HSV-1-infected mDCs we identified 41 viral proteins which are differentially distributed compared to L-particles from BHK21 cells. In this study, we present data suggesting that L-particles modify mDCs and suppress their T cell stimulatory capacity. Due to the plethora of specific viral proteins incorporated into and transmitted by L-particles, it is tempting to speculate that L-particles manipulate non-infected bystander cells for the benefit of the virus.

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Host Intrinsic and Innate Intracellular Immunity During Herpes Simplex Virus Type 1 (HSV-1) Infection

Cited by 40 publications

References 215 publications

The HSV-1 ubiquitin ligase ICP0: Modifying the cellular proteome to promote infection

The HSV-1 ubiquitin ligase ICP0: Modifying the cellular proteome to promote infection

Replication Compartments of DNA Viruses in the Nucleus: Location, Location, Location

Mass Spectrometric Characterization of HSV-1 L-Particles From Human Dendritic Cells and BHK21 Cells and Analysis of Their Functional Role

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