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Intracellular Organelle Rearrangement Induced by Pathogenic Infections

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 39527

Special Issue Editor


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Guest Editor
Department of Biochemistry and Molecular Biology, Faculty of Agriculture and Life Science, Hirosaki University, 3 Bunkyo-cho, Hirosaki-shi, Aomori 036-8561, Japan
Interests: viral replication organelle; viral assembly; viral budding; selective autophagy; endoplasmic reticulum membrane rearrangement; innate immune responses

Special Issue Information

Dear Colleagues,

Many pathogens have evolved to assume an intracellular mode of infection for their growth and replication; however, several intracellular antipathogen responses potentially prevent the growth of pathogens, or sometimes these responses lead to the elimination of intracellular pathogens. Recent studies have reported that molecules localized in organelle regulate these antipathogen responses, and intracellular pathogens induce the dynamic rearrangement of organelles to modify or sometimes neutralize its functions for their efficient growth. For example, some bacteria modify lysosomal membrane components for their propagation within these intracellular compartments. Several viruses remodel the endoplasmic reticulum or Golgi membranes and generate a new intracellular compartment for efficient replication of their genome and viral assembly. Furthermore, some bacteria modify autophagic machinery to disable the antibacterial response of the cell, and viruses damage mitochondrial proteins involved in innate immune signaling to neutralize antiviral responses.

This Special Issue focuses on organellar rearrangement resulting from the competitive survival of intracellular parasites and to understand the molecular mechanisms underlying the development of novel antipathogen strategies.

Dr. Eiji Morita
Guest Editor

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Keywords

  • Organellar rearrangement
  • Intracellular pathogenic infection
  • Anti-innate immune response
  • Pathogen-inducing organelle
  • Cellular stress responses

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Published Papers (8 papers)

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Research

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14 pages, 6241 KiB  
Article
Lipid Droplet Motility Increases Following Viral Immune Stimulation
by Ebony A. Monson, Donna R. Whelan and Karla J. Helbig
Int. J. Mol. Sci. 2021, 22(9), 4418; https://doi.org/10.3390/ijms22094418 - 23 Apr 2021
Cited by 12 | Viewed by 4248
Abstract
Lipid droplets (LDs) have traditionally been thought of as solely lipid storage compartments for cells; however, in the last decade, they have emerged as critical organelles in health and disease. LDs are highly dynamic within cells, and their movement is critical in organelle–organelle [...] Read more.
Lipid droplets (LDs) have traditionally been thought of as solely lipid storage compartments for cells; however, in the last decade, they have emerged as critical organelles in health and disease. LDs are highly dynamic within cells, and their movement is critical in organelle–organelle interactions. Their dynamics are known to change during cellular stress or nutrient deprivation; however, their movement during pathogen infections, especially at very early timepoints, is under-researched. This study aimed to track LD dynamics in vitro, in an astrocytic model of infection. Cells were either stimulated with a dsRNA viral mimic, poly I:C, or infected with the RNA virus, Zika virus. Individual LDs within infected cells were analysed to determine displacement and speed, and average LD characteristics for multiple individual cells calculated. Both LD displacement and mean speed were significantly enhanced in stimulated cells over a time course of infection with an increase seen as early as 2 h post-infection. With the emerging role for LDs during innate host responses, understanding their dynamics is critical to elucidate how these organelles influence the outcome of viral infection. Full article
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16 pages, 2939 KiB  
Article
Chlamydia psittaci PmpD-N Modulated Chicken Macrophage Function by Triggering Th2 Polarization and the TLR2/MyD88/NF-κB Signaling Pathway
by Jun Chu, Xiaohui Li, Guanggang Qu, Yihui Wang, Qiang Li, Yongxia Guo, Lei Hou, Jue Liu, Francis O. Eko and Cheng He
Int. J. Mol. Sci. 2020, 21(6), 2003; https://doi.org/10.3390/ijms21062003 - 15 Mar 2020
Cited by 15 | Viewed by 3440 | Correction
Abstract
The polymorphic membrane protein D (PmpD) is a highly conserved outer membrane protein which plays an important role in pathogenesis during Chlamydia psittaci infection. In this study, we evaluated the ability of the N-terminus of PmpD (PmpD-N) to modulate the functions of chicken [...] Read more.
The polymorphic membrane protein D (PmpD) is a highly conserved outer membrane protein which plays an important role in pathogenesis during Chlamydia psittaci infection. In this study, we evaluated the ability of the N-terminus of PmpD (PmpD-N) to modulate the functions of chicken macrophages and the signaling pathway(s) involved in PmpD-N-induced Toll-like receptors (TLRs), as well as interleukin (IL)-6 and IL-10 cytokine secretions. Thus, HD11 macrophages were treated with exogenous and intracellular PmpD-N of C. psittaci. The chlamydial growth was evaluated by enumeration of chlamydial loads in the infected macrophages. The phagocytic function of macrophages following PmpD-N treatment was detected by fluorescein-labeled Escherichia coli (E. coli). The concentration of nitric oxide (NO) secreted by HD11 macrophages was measured by the amount of NO2- in the culture supernatant using the Griess method. The cytokine secretions were assessed using multiplex cytokine ELISA kits. Expression levels of TLRs, myeloid differentiation factor 88 (MyD88), and nuclear factor kappa B (NF-κB) were analyzed by a Western blotting assay, as well as a luciferase assay, while NF-κB p65 nuclear translocation was assessed by confocal microscopy. The nuclear translocation of the transcription factor NF-κB was confirmed by evaluating its ability to combine with the corresponding promoter using the electrophoretic mobility shift assay (EMSA). After treatment with exogenous or endogenous PmpD-N, chlamydial loads and phagocytic functions were reduced significantly compared with those of the plasmid vector group, while NO secretions were reduced significantly compared with those of the lipopolysaccharide (LPS) treatment. Stimulation of HD11 cells with PmpD-N provoked the secretion of the Th2 cytokines, IL-6, and IL-10 and upregulated the expression of TLR2, TLR4, MyD88, and NF-κB. Furthermore, inhibition of TLR2, MyD88, and NF-κB in HD11 cells significantly decreased IL-6 and IL-10 cytokine levels, while NO production and phagocytosis increased significantly, strongly suggesting their involvement in PmpD-N-induced Th2 cytokine secretion and macrophage dysfunction. Our data indicate that C. psittaci PmpD-N inhibited macrophage functions by activating the Th2 immune response and the TLR2/MyD88/NF-κB signaling pathway. Full article
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Review

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23 pages, 2644 KiB  
Review
Manipulation of Host Cell Organelles by Intracellular Pathogens
by Malte Kellermann, Felix Scharte and Michael Hensel
Int. J. Mol. Sci. 2021, 22(12), 6484; https://doi.org/10.3390/ijms22126484 - 17 Jun 2021
Cited by 28 | Viewed by 9172
Abstract
Pathogenic intracellular bacteria, parasites and viruses have evolved sophisticated mechanisms to manipulate mammalian host cells to serve as niches for persistence and proliferation. The intracellular lifestyles of pathogens involve the manipulation of membrane-bound organellar compartments of host cells. In this review, we described [...] Read more.
Pathogenic intracellular bacteria, parasites and viruses have evolved sophisticated mechanisms to manipulate mammalian host cells to serve as niches for persistence and proliferation. The intracellular lifestyles of pathogens involve the manipulation of membrane-bound organellar compartments of host cells. In this review, we described how normal structural organization and cellular functions of endosomes, endoplasmic reticulum, Golgi apparatus, mitochondria, or lipid droplets are targeted by microbial virulence mechanisms. We focus on the specific interactions of Salmonella, Legionella pneumophila, Rickettsia rickettsii, Chlamydia spp. and Mycobacterium tuberculosis representing intracellular bacterial pathogens, and of Plasmodium spp. and Toxoplasma gondii representing intracellular parasites. The replication strategies of various viruses, i.e., Influenza A virus, Poliovirus, Brome mosaic virus, Epstein-Barr Virus, Hepatitis C virus, severe acute respiratory syndrome virus (SARS), Dengue virus, Zika virus, and others are presented with focus on the specific manipulation of the organelle compartments. We compare the specific features of intracellular lifestyle and replication cycles, and highlight the communalities in mechanisms of manipulation deployed. Full article
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26 pages, 1393 KiB  
Review
Viral Interactions with Adaptor-Protein Complexes: A Ubiquitous Trait among Viral Species
by Ivana Strazic Geljic, Paola Kucan Brlic, Lucija Musak, Dubravka Karner, Andreja Ambriović-Ristov, Stipan Jonjic, Peter Schu and Tihana Lenac Rovis
Int. J. Mol. Sci. 2021, 22(10), 5274; https://doi.org/10.3390/ijms22105274 - 17 May 2021
Cited by 8 | Viewed by 4532
Abstract
Numerous viruses hijack cellular protein trafficking pathways to mediate cell entry or to rearrange membrane structures thereby promoting viral replication and antagonizing the immune response. Adaptor protein complexes (AP), which mediate protein sorting in endocytic and secretory transport pathways, are one of the [...] Read more.
Numerous viruses hijack cellular protein trafficking pathways to mediate cell entry or to rearrange membrane structures thereby promoting viral replication and antagonizing the immune response. Adaptor protein complexes (AP), which mediate protein sorting in endocytic and secretory transport pathways, are one of the conserved viral targets with many viruses possessing AP-interacting motifs. We present here different mechanisms of viral interference with AP complexes and the functional consequences that allow for efficient viral propagation and evasion of host immune defense. The ubiquity of this phenomenon is evidenced by the fact that there are representatives for AP interference in all major viral families, covered in this review. The best described examples are interactions of human immunodeficiency virus and human herpesviruses with AP complexes. Several other viruses, like Ebola, Nipah, and SARS-CoV-2, are pointed out as high priority disease-causative agents supporting the need for deeper understanding of virus-AP interplay which can be exploited in the design of novel antiviral therapies. Full article
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14 pages, 1991 KiB  
Review
SEIPIN: A Key Factor for Nuclear Lipid Droplet Generation and Lipid Homeostasis
by Yi Jin, Yanjie Tan, Pengxiang Zhao and Zhuqing Ren
Int. J. Mol. Sci. 2020, 21(21), 8208; https://doi.org/10.3390/ijms21218208 - 2 Nov 2020
Cited by 18 | Viewed by 4623
Abstract
Lipid homeostasis is essential for normal cell physiology. Generally, lipids are stored in a lipid droplet (LD), a ubiquitous organelle consisting of a neutral lipid core and a single layer of phospholipid membrane. It is thought that LDs are generated from the endoplasmic [...] Read more.
Lipid homeostasis is essential for normal cell physiology. Generally, lipids are stored in a lipid droplet (LD), a ubiquitous organelle consisting of a neutral lipid core and a single layer of phospholipid membrane. It is thought that LDs are generated from the endoplasmic reticulum and then released into the cytosol. Recent studies indicate that LDs can exist in the nucleus, where they play an important role in the maintenance of cell phospholipid homeostasis. However, the details of nuclear lipid droplet (nLD) generation have not yet been clearly characterized. SEIPIN is a nonenzymatic protein encoded by the Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) gene. It is associated with lipodystrophy diseases. Many recent studies have indicated that SEIPIN is essential for LDs generation. Here, we review much of this research in an attempt to explain the role of SEIPIN in nLD generation. From an integrative perspective, we conclude by proposing a theoretical model to explain how SEIPIN might participate in maintaining homeostasis of lipid metabolism. Full article
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18 pages, 2188 KiB  
Review
Hijacking of Lipid Droplets by Hepatitis C, Dengue and Zika Viruses—From Viral Protein Moonlighting to Extracellular Release
by Alexandra P.M. Cloherty, Andrea D. Olmstead, Carla M.S. Ribeiro and François Jean
Int. J. Mol. Sci. 2020, 21(21), 7901; https://doi.org/10.3390/ijms21217901 - 24 Oct 2020
Cited by 51 | Viewed by 6197
Abstract
Hijacking and manipulation of host cell biosynthetic pathways by human enveloped viruses are essential for the viral lifecycle. Flaviviridae members, including hepatitis C, dengue and Zika viruses, extensively manipulate host lipid metabolism, underlining the importance of lipid droplets (LDs) in viral infection. LDs [...] Read more.
Hijacking and manipulation of host cell biosynthetic pathways by human enveloped viruses are essential for the viral lifecycle. Flaviviridae members, including hepatitis C, dengue and Zika viruses, extensively manipulate host lipid metabolism, underlining the importance of lipid droplets (LDs) in viral infection. LDs are dynamic cytoplasmic organelles that can act as sequestration platforms for a unique subset of host and viral proteins. Transient recruitment and mobilization of proteins to LDs during viral infection impacts host-cell biological properties, LD functionality and canonical protein functions. Notably, recent studies identified LDs in the nucleus and also identified that LDs are transported extracellularly via an autophagy-mediated mechanism, indicating a novel role for autophagy in Flaviviridae infections. These developments underline an unsuspected diversity and localization of LDs and potential moonlighting functions of LD-associated proteins during infection. This review summarizes recent breakthroughs concerning the LD hijacking activities of hepatitis C, dengue and Zika viruses and potential roles of cytoplasmic, nuclear and extracellular LD-associated viral proteins during infection. Full article
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26 pages, 2254 KiB  
Review
Morphology Remodeling and Selective Autophagy of Intracellular Organelles during Viral Infections
by Shanhui Ren, Chan Ding and Yingjie Sun
Int. J. Mol. Sci. 2020, 21(10), 3689; https://doi.org/10.3390/ijms21103689 - 23 May 2020
Cited by 10 | Viewed by 3887
Abstract
Viruses have evolved different strategies to hijack subcellular organelles during their life cycle to produce robust infectious progeny. Successful viral reproduction requires the precise assembly of progeny virions from viral genomes, structural proteins, and membrane components. Such spatial and temporal separation of assembly [...] Read more.
Viruses have evolved different strategies to hijack subcellular organelles during their life cycle to produce robust infectious progeny. Successful viral reproduction requires the precise assembly of progeny virions from viral genomes, structural proteins, and membrane components. Such spatial and temporal separation of assembly reactions depends on accurate coordination among intracellular compartmentalization in multiple organelles. Here, we overview the rearrangement and morphology remodeling of virus-triggered intracellular organelles. Focus is given to the quality control of intracellular organelles, the hijacking of the modified organelle membranes by viruses, morphology remodeling for viral replication, and degradation of intracellular organelles by virus-triggered selective autophagy. Understanding the functional reprogram and morphological remodeling in the virus-organelle interplay can provide new insights into the development of broad-spectrum antiviral strategies. Full article
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Other

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2 pages, 177 KiB  
Correction
Correction:Chlamydia psittaci PmpD-N Modulated Chicken Macrophage Function by Triggering Th2 Polarization and the TLR2/MyD88/NF-κB Signaling Pathway
by Jun Chu, Xiaohui Li, Guanggang Qu, Yihui Wang, Qiang Li, Yongxia Guo, Lei Hou, Jue Liu, Francis O. Eko and Cheng He
Int. J. Mol. Sci. 2020, 21(7), 2639; https://doi.org/10.3390/ijms21072639 - 10 Apr 2020
Cited by 2 | Viewed by 2086
Abstract
The authors would like to make the following corrections to their paper, published in the International Journal of Molecular Sciences [...] Full article
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