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The Interaction between Cell and Virus

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

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 37582

Special Issue Editor


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Guest Editor
Department of Cell Biology, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan
Interests: human herpesviruses; Kaposi's sarcoma-associated herpesvirus (KSHV); herpes simplex virus (HSV); cell signaling pathways; dengue virus (DENV); post-translational modification; proteasome; ubiquitin; protein degradation
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Special Issue Information

Dear Colleagues,

Viral infections cause various diseases in the host species. Antiviral medications can help to relieve the symptoms of some viruses by inhibiting viral enzymes or virus-mediated events. However, during the past half century, very few antiviral drugs (excluding anti-HCV drugs) have been developed for use in the treatment of serious and life-threatening viral infections.

A fundamental step for the effective infection and replication of all viruses is the interaction between cell and virus. This is achieved through the dysregulation and exploitation of host cell functions (e.g., gene expression, signal transduction, metabolic process, intracellular transport, organelle biogenesis or communication, apoptosis, protein degradation, and immune response) by viral molecules, such as viral proteins and microRNA. Viruses hijack the appropriate cellular functions for establishment of infection, persistent infection, prolonging survival, control of cell proliferation, anti-apoptosis, and evasion of immune surveillance in infected cells. Viruses manipulate those cellular functions in order to create a favorable environment for the virus or the virus-infected cell. On the other hand, the host species exerts antiviral effects on virus infection through the interaction between cell and virus.

A better understanding of the interaction between viruses and host cells could provide new insights into the process of pathogenesis, immune disruption (or activation), and tumorigenesis triggered by viruses and may provide a theoretical basis for the development of novel therapeutic interventions against infectious diseases.

For this Special Issue, original research articles, review articles and short communications are welcome. Research areas of interest include the cell–virus interaction involved in viral replication, gene expression, latent or lytic infection, viral structural protein and enzyme, virus assembly, cell signaling pathway, post-translational modification, host factor, virus immune evasion, host immune response, viral tumorigenesis or disease, antiviral medication, vaccine, animal model, and gene therapy.

Prof. Dr. Masahiro Fujimuro
Guest Editor

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Keywords

  • viral replication
  • gene expression
  • lytic infection
  • viral structure
  • viral assembly
  • cell signaling pathway
  • post-translational modification
  • immune evasion
  • viral tumorigenesis
  • antiviral medication

Published Papers (16 papers)

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Research

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17 pages, 2046 KiB  
Communication
Transcriptomic Analysis Reveals the Inability of Recombinant AAV8 to Activate Human Monocyte-Derived Dendritic Cells
by Samer Masri, Laure Carré, Nicolas Jaulin, Céline Vandamme, Célia Couzinié, Aurélien Guy-Duché, Jean-Baptiste Dupont, Allwyn Pereira, Eric Charpentier, Laurent David, Gwladys Gernoux, Mickaël Guilbaud and Oumeya Adjali
Int. J. Mol. Sci. 2023, 24(13), 10447; https://doi.org/10.3390/ijms241310447 - 21 Jun 2023
Viewed by 1161
Abstract
Recombinant Adeno-Associated Virus (rAAV) is considered as one of the most successful and widely used viral vectors for in vivo gene therapy. However, host immune responses to the vector and/or the transgene product remain a major hurdle to successful AAV gene transfer. In [...] Read more.
Recombinant Adeno-Associated Virus (rAAV) is considered as one of the most successful and widely used viral vectors for in vivo gene therapy. However, host immune responses to the vector and/or the transgene product remain a major hurdle to successful AAV gene transfer. In contrast to antivector adaptive immunity, the initiation of the innate immunity towards rAAV is still poorly understood but is directly dependent on the interaction between the viral vector and innate immune cells. Here, we used a quantitative transcriptomic-based approach to determine the activation of inflammatory and anti-viral pathways after rAAV8-based infection of monocyte-derived dendritic cells (moDCs) obtained from 12 healthy human donors. We have shown that rAAV8 particles are efficiently internalized, but that this uptake does not induce any detectable transcriptomic change in moDCs in contrast to an adenoviral infection, which upregulates anti-viral pathways. These findings suggest an immunologically favorable profile for rAAV8 serotype with regard to in vitro activation of moDC model. Transcriptomic analysis of rAAV-infected innate immune cells is a powerful method to determine the ability of the viral vector to be seen by these sensor cells, which remains of great importance to better understand the immunogenicity of rAAV vectors and to design immune-stealth products. Full article
(This article belongs to the Special Issue The Interaction between Cell and Virus)
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15 pages, 11355 KiB  
Article
Feline Calicivirus P39 Inhibits Innate Immune Responses by Autophagic Degradation of Retinoic Acid Inducible Gene I
by Jianwei Mao, Shaotang Ye, Jie Deng, Jie Song, Zhen Wang, Aolei Chen, Pei Zhou and Shoujun Li
Int. J. Mol. Sci. 2023, 24(6), 5254; https://doi.org/10.3390/ijms24065254 - 09 Mar 2023
Viewed by 1783
Abstract
Feline calicivirus (FCV) is a feline pathogen that can cause severe upper respiratory tract disease in cats, thus posing a major threat to their health. The exact pathogenic mechanism of FCV is still unclear, although it has been identified as having the ability [...] Read more.
Feline calicivirus (FCV) is a feline pathogen that can cause severe upper respiratory tract disease in cats, thus posing a major threat to their health. The exact pathogenic mechanism of FCV is still unclear, although it has been identified as having the ability to induce immune depression. In this study, we discovered that FCV infection triggers autophagy and that its non-structural proteins, P30, P32, and P39, are responsible for initiating this process. Additionally, we observed that altering autophagy levels via chemical modulation resulted in different influences on FCV replication. Moreover, our findings indicate that autophagy can modify the innate immunity induced by FCV infection, with increased autophagy further suppressing FCV-induced RIG-I signal transduction. This research provides insights into the mechanism of FCV replication and has the potential to aid in the development of autophagy-targeted drugs to inhibit or prevent FCV infection. Full article
(This article belongs to the Special Issue The Interaction between Cell and Virus)
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12 pages, 2756 KiB  
Article
N6-methyladenosine Modification of Hepatitis B Virus RNA in the Coding Region of HBx
by Takayuki Murata, Satoko Iwahori, Yusuke Okuno, Hironori Nishitsuji, Yusuke Yanagi, Koichi Watashi, Takaji Wakita, Hiroshi Kimura and Kunitada Shimotohno
Int. J. Mol. Sci. 2023, 24(3), 2265; https://doi.org/10.3390/ijms24032265 - 23 Jan 2023
Viewed by 1742
Abstract
N6-methyladenosine (m6A) is a post-transcriptional modification of RNA involved in transcript transport, degradation, translation, and splicing. We found that HBV RNA is modified by m6A predominantly in the coding region of HBx. The mutagenesis of methylation sites reduced [...] Read more.
N6-methyladenosine (m6A) is a post-transcriptional modification of RNA involved in transcript transport, degradation, translation, and splicing. We found that HBV RNA is modified by m6A predominantly in the coding region of HBx. The mutagenesis of methylation sites reduced the HBV mRNA and HBs protein levels. The suppression of m6A by an inhibitor or knockdown in primary hepatocytes decreased the viral RNA and HBs protein levels in the medium. These results suggest that the m6A modification of HBV RNA is needed for the efficient replication of HBV in hepatocytes. Full article
(This article belongs to the Special Issue The Interaction between Cell and Virus)
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18 pages, 6907 KiB  
Article
Metabolomics Profiles Reveal New Insights of Herpes Simplex Virus Type 1 Infection
by Pu Huang, Xu Wang, Mengyue Lei, Ying Ma, Hongli Chen, Jing Sun, Yunzhang Hu and Jiandong Shi
Int. J. Mol. Sci. 2023, 24(2), 1521; https://doi.org/10.3390/ijms24021521 - 12 Jan 2023
Cited by 3 | Viewed by 2574
Abstract
Herpes simplex virus type 1 (HSV-1) is a ubiquitous human pathogen that can cause significant morbidity, primarily facial cold sores and herpes simplex encephalitis. Previous studies have shown that a variety of viruses can reprogram the metabolic profiles of host cells to facilitate [...] Read more.
Herpes simplex virus type 1 (HSV-1) is a ubiquitous human pathogen that can cause significant morbidity, primarily facial cold sores and herpes simplex encephalitis. Previous studies have shown that a variety of viruses can reprogram the metabolic profiles of host cells to facilitate self-replication. In order to further elucidate the metabolic interactions between the host cell and HSV-1, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze the metabolic profiles in human lung fibroblasts KMB17 infected with HSV-1. The results showed that 654 and 474 differential metabolites were identified in positive and negative ion modes, respectively, and 169 and 114 metabolic pathways that might be altered were screened. These altered metabolites are mainly involved in central carbon metabolism, choline metabolism, amino acid metabolism, purine and pyrimidine metabolism, cholesterol metabolism, bile secretion, and prolactin signaling pathway. Further, we confirmed that the addition of tryptophan metabolite kynurenine promotes HSV-1 replication, and the addition of 25-Hydroxycholesterol inhibits viral replication. Significantly, HSV-1 replication was obviously enhanced in the ChOKα (a choline metabolic rate-limiting enzyme) deficient mouse macrophages. These results indicated that HSV-1 induces the metabolic reprogramming of host cells to promote or resist viral replication. Taken together, these observations highlighted the significance of host cell metabolism in HSV-1 replication, which would help to clarify the pathogenesis of HSV-1 and identify new anti-HSV-1 therapeutic targets. Full article
(This article belongs to the Special Issue The Interaction between Cell and Virus)
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13 pages, 2409 KiB  
Article
SARS-CoV-2 Spike Protein Mutation at Cysteine-488 Impairs Its Golgi Localization and Intracellular S1/S2 Processing
by Yuichiro Yamamoto, Tetsuya Inoue, Miyu Inoue, Mana Murae, Masayoshi Fukasawa, Mika K. Kaneko, Yukinari Kato and Kohji Noguchi
Int. J. Mol. Sci. 2022, 23(24), 15834; https://doi.org/10.3390/ijms232415834 - 13 Dec 2022
Cited by 3 | Viewed by 2683
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to the cellular receptor—angiotensin-converting enzyme-2 (ACE2) as the first step in viral cell entry. SARS-CoV-2 spike protein expression in the ACE2-expressing cell surface induces cell–cell membrane fusion, thus forming syncytia. To exert [...] Read more.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to the cellular receptor—angiotensin-converting enzyme-2 (ACE2) as the first step in viral cell entry. SARS-CoV-2 spike protein expression in the ACE2-expressing cell surface induces cell–cell membrane fusion, thus forming syncytia. To exert its fusogenic activity, the spike protein is typically processed at a specific site (the S1/S2 site) by cellular proteases such as furin. The C488 residue, located at the spike–ACE2 interacting surface, is critical for the fusogenic and infectious roles of the SARS-CoV-2 spike protein. We have demonstrated that the C488 residue of the spike protein is involved in subcellular targeting and S1/S2 processing. C488 mutant spike localization to the Golgi apparatus and cell surface were impaired. Consequently, the S1/S2 processing of the spike protein, probed by anti-Ser-686-cleaved spike antibody, markedly decreased in C488 mutant spike proteins. Moreover, brefeldin-A-mediated endoplasmic-reticulum-to-Golgi traffic suppression also suppressed spike protein S1/S2 processing. As brefeldin A treatment and C488 mutation inhibited S1/S2 processing and syncytia formation, the C488 residue of spike protein is required for functional spike protein processing. Full article
(This article belongs to the Special Issue The Interaction between Cell and Virus)
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18 pages, 5548 KiB  
Article
Regulation of Epstein-Barr Virus Minor Capsid Protein BORF1 by TRIM5α
by Lih-Tsern Lin, Yi-Shan Lu, Hsiang-Hung Huang, Hao Chen, Shih-Wei Hsu and Li-Kwan Chang
Int. J. Mol. Sci. 2022, 23(23), 15340; https://doi.org/10.3390/ijms232315340 - 05 Dec 2022
Cited by 1 | Viewed by 1812
Abstract
TRIM5α is a host anti-retroviral restriction factor that destroys human immunodeficiency virus (HIV) virions and triggers innate immune signaling. TRIM5α also mediates the autophagic degradation of target proteins via TRIMosome formation. We previously showed that TRIM5α promotes Epstein-Barr virus (EBV) Rta ubiquitination and [...] Read more.
TRIM5α is a host anti-retroviral restriction factor that destroys human immunodeficiency virus (HIV) virions and triggers innate immune signaling. TRIM5α also mediates the autophagic degradation of target proteins via TRIMosome formation. We previously showed that TRIM5α promotes Epstein-Barr virus (EBV) Rta ubiquitination and attenuates EBV lytic progression. In this study, we sought to elucidate whether TRIM5α can interact with and induce the degradation of EBV capsid proteins. Glutathione S-transferase (GST) pulldown and immunoprecipitation assays were conducted to identify interacting proteins, and mutants were generated to investigate key binding domains and ubiquitination sites. Results showed that TRIM5α binds directly with BORF1, an EBV capsid protein with a nuclear localization signal (NLS) that enables the transport of EBV capsid proteins into the host nucleus to facilitate capsid assembly. TRIM5α promotes BORF1 ubiquitination, which requires the surface patch region in the TRIM5α PRY/SPRY domain. TRIM5α expression also decreases the stability of BORF1(6KR), a mutant with all lysine residues mutated to arginine. However, chloroquine treatment restores the stability of BORF1(6KR), suggesting that TRIM5α destabilizes BORF1 via direct recognition of its substrate for autophagic degradation. These results reveal novel insights into the antiviral impact of TRIM5α beyond retroviruses. Full article
(This article belongs to the Special Issue The Interaction between Cell and Virus)
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10 pages, 1584 KiB  
Communication
MC180295 Inhibited Epstein–Barr Virus-Associated Gastric Carcinoma Cell Growth by Suppressing DNA Repair and the Cell Cycle
by Tomohiro Fujii, Jun Nishikawa, Soichiro Fukuda, Naoto Kubota, Junzo Nojima, Koichi Fujisawa, Ryo Ogawa, Atsushi Goto, Koichi Hamabe, Shinichi Hashimoto, Aung Phyo Wai, Hisashi Iizasa, Hironori Yoshiyama, Kohei Sakai, Yutaka Suehiro, Takahiro Yamasaki and Taro Takami
Int. J. Mol. Sci. 2022, 23(18), 10597; https://doi.org/10.3390/ijms231810597 - 13 Sep 2022
Cited by 2 | Viewed by 1892
Abstract
DNA methylation of both viral and host DNA is one of the major mechanisms involved in the development of Epstein–Barr virus-associated gastric carcinoma (EBVaGC); thus, epigenetic treatment using demethylating agents would seem to be promising. We have verified the effect of MC180295, which [...] Read more.
DNA methylation of both viral and host DNA is one of the major mechanisms involved in the development of Epstein–Barr virus-associated gastric carcinoma (EBVaGC); thus, epigenetic treatment using demethylating agents would seem to be promising. We have verified the effect of MC180295, which was discovered by screening for demethylating agents. MC180295 inhibited cell growth of the EBVaGC cell lines YCCEL1 and SNU719 in a dose-dependent manner. In a cell cycle analysis, growth arrest and apoptosis were observed in both YCCEL1 and SNU719 cells treated with MC180295. MKN28 cells infected with EBV were sensitive to MC180295 and showed more significant inhibition of cell growth compared to controls without EBV infection. Serial analysis of gene expression analysis showed the expression of genes belonging to the role of BRCA1 in DNA damage response and cell cycle control chromosomal replication to be significantly reduced after MC180295 treatment. We confirmed with quantitative PCR that the expression levels of BRCA2, FANCM, RAD51, TOP2A, and CDC45 were significantly decreased by MC180295. LMP1 and BZLF1 are EBV genes with expression that is epigenetically regulated, and MC180295 could up-regulate their expression. In conclusion, MC180295 inhibited the growth of EBVaGC cells by suppressing DNA repair and the cell cycle. Full article
(This article belongs to the Special Issue The Interaction between Cell and Virus)
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16 pages, 3732 KiB  
Article
Biomolecular Fluorescence Complementation Profiling and Artificial Intelligence Structure Prediction of the Kaposi’s Sarcoma-Associated Herpesvirus ORF18 and ORF30 Interaction
by Yoshiko Maeda, Tadashi Watanabe, Taisuke Izumi, Kazushi Kuriyama, Shinji Ohno and Masahiro Fujimuro
Int. J. Mol. Sci. 2022, 23(17), 9647; https://doi.org/10.3390/ijms23179647 - 25 Aug 2022
Cited by 4 | Viewed by 1538
Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi’s sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman’s disease. During KSHV lytic infection, lytic-related genes, categorized as immediate-early, early, and late genes, are expressed in a temporal manner. The transcription of late genes [...] Read more.
Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi’s sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman’s disease. During KSHV lytic infection, lytic-related genes, categorized as immediate-early, early, and late genes, are expressed in a temporal manner. The transcription of late genes requires the virus-specific pre-initiation complex (vPIC), which consists of viral transcription factors. However, the protein-protein interactions of the vPIC factors have not been completely elucidated. KSHV ORF18 is one of the vPIC factors, and its interaction with other viral proteins has not been sufficiently revealed. In order to clarify these issues, we analyzed the interaction between ORF18 and another vPIC factor, ORF30, in living cells using the bimolecular fluorescence complementation (BiFC) assay. We identified four amino-acid residues (Leu29, Glu36, His41, and Trp170) of ORF18 that were responsible for its interaction with ORF30. Pull-down assays also showed that these four residues were required for the ORF18-ORF30 interaction. The artificial intelligence (AI) system AlphaFold2 predicted that the identified four residues are localized on the surface of ORF18 and are in proximity to each other. Thus, our AI-predicted model supports the importance of the four residues for binding ORF18 to ORF30. These results indicated that wet experiments in combination with AI may enhance the structural characterization of vPIC protein-protein interactions. Full article
(This article belongs to the Special Issue The Interaction between Cell and Virus)
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14 pages, 1845 KiB  
Article
ATP5B Is an Essential Factor for Hepatitis B Virus Entry
by Keiji Ueda and Yadarat Suwanmanee
Int. J. Mol. Sci. 2022, 23(17), 9570; https://doi.org/10.3390/ijms23179570 - 24 Aug 2022
Cited by 1 | Viewed by 2075
Abstract
Elucidation of the factors responsible for hepatitis B virus (HBV) is extremely important in order to understand the viral life cycle and pathogenesis, and thereby explore potential anti-HBV drugs. The recent determination that sodium taurocholate co-transporting peptide (NTCP) is an essential molecule for [...] Read more.
Elucidation of the factors responsible for hepatitis B virus (HBV) is extremely important in order to understand the viral life cycle and pathogenesis, and thereby explore potential anti-HBV drugs. The recent determination that sodium taurocholate co-transporting peptide (NTCP) is an essential molecule for the HBV entry into cells led to the development of an HBV infection system in vitro using a human hepatocellular carcinoma (HCC) cell line expressing NTCP; however, the precise mechanism of HBV entry is still largely unknown, and thus it may be necessary to elucidate all the molecules involved. Here, we identified ATP5B as another essential factor for HBV entry. ATP5B was expressed on the cell surface of the HCC cell lines and bound with myristoylated but not with non-myristoylated preS1 2-47, which supported the notion that ATP5B is involved in the HBV entry process. Knockdown of ATP5B in NTCP-expressing HepG2 cells, which allowed HBV infection, reduced HBV infectivity with less cccDNA formation. Taken together, these results strongly suggested that ATP5B is an essential factor for HBV entry into the cells. Full article
(This article belongs to the Special Issue The Interaction between Cell and Virus)
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15 pages, 4036 KiB  
Article
PCV2 and PRV Coinfection Induces Endoplasmic Reticulum Stress via PERK-eIF2α-ATF4-CHOP and IRE1-XBP1-EDEM Pathways
by Si Chen, Xue Li, Xinwei Zhang, Guyu Niu, Lin Yang, Weilong Ji, Liying Zhang and Linzhu Ren
Int. J. Mol. Sci. 2022, 23(9), 4479; https://doi.org/10.3390/ijms23094479 - 19 Apr 2022
Cited by 4 | Viewed by 2642
Abstract
Porcine circovirus 2 (PCV2) and pseudorabies virus (PRV) are two important pathogens in the pig industry. PCV2 or PRV infection can induce endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). However, the effect of PCV2 and PRV coinfection on the ERS and [...] Read more.
Porcine circovirus 2 (PCV2) and pseudorabies virus (PRV) are two important pathogens in the pig industry. PCV2 or PRV infection can induce endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). However, the effect of PCV2 and PRV coinfection on the ERS and UPR pathways remains unclear. In this study, we found that PRV inhibited the proliferation of PCV2 mainly at 36 to 72 hpi, while PCV2 enhanced the proliferation of PRV in the middle stage of the infection. Notably, PRV is the main factor during coinfection. The results of the transcriptomic analysis showed that coinfection with PCV2 and PRV activated cellular ERS, and upregulated expressions of the ERS pathway-related proteins, including GRP78, eIF2α, and ATF4. Further research indicated that PRV played a dominant role in the sequential infection and coinfection of PCV2 and PRV. PCV2 and PRV coinfection induced the ERS activation via the PERK-eIF2α-ATF4-CHOP axis and IRE1-XBP1-EDEM pathway, and thus may enhance cell apoptosis and exacerbate the diseases. Full article
(This article belongs to the Special Issue The Interaction between Cell and Virus)
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16 pages, 3912 KiB  
Article
Coinfection of Porcine Circovirus 2 and Pseudorabies Virus Enhances Immunosuppression and Inflammation through NF-κB, JAK/STAT, MAPK, and NLRP3 Pathways
by Xue Li, Si Chen, Liying Zhang, Guyu Niu, Xinwei Zhang, Lin Yang, Weilong Ji and Linzhu Ren
Int. J. Mol. Sci. 2022, 23(8), 4469; https://doi.org/10.3390/ijms23084469 - 18 Apr 2022
Cited by 18 | Viewed by 2935
Abstract
Porcine circovirus 2 (PCV2) and pseudorabies virus (PRV) are economically important pathogens in swine. PCV2 and PRV coinfection can cause more severe neurological and respiratory symptoms and higher mortality of piglets. However, the exact mechanism involved in the coinfection of PRV and PCV2 [...] Read more.
Porcine circovirus 2 (PCV2) and pseudorabies virus (PRV) are economically important pathogens in swine. PCV2 and PRV coinfection can cause more severe neurological and respiratory symptoms and higher mortality of piglets. However, the exact mechanism involved in the coinfection of PRV and PCV2 and its pathogenesis remain unknown. Here, porcine kidney cells (PK-15) were infected with PCV2 and/or PRV, and then the activation of immune and inflammatory pathways was evaluated to clarify the influence of the coinfection on immune and inflammatory responses. We found that the coinfection of PCV2 and PRV can promote the activation of nuclear factor-κB (NF-κB), c-Jun N-terminal protein kinases (JNK), p38, and nod-like receptor protein 3 (NLRP3) pathways, thus enhancing the expression of interferon-γ (IFN-γ), interferon-λ1 (IFN-λ1), interferon-stimulated gene (ISG15), interleukin 6 (IL6), and interleukin 1β (IL1β). Meanwhile, PCV2 and PRV also inhibit the expression and signal transduction of IFN-β, tumor necrosis factor α (TNFα), and the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway. In addition, PCV2 and PRV infection can also weaken extracellular-signal-regulated kinase (ERK) activity. These results indicate that the regulations of cellular antiviral immune responses and inflammatory responses mediated by NF-κB, JAK/STAT, mitogen-activated protein kinase (MAPK), and NLRP3 pathways, contribute to immune escape of PCV2 and PRV and host antiviral responses. Full article
(This article belongs to the Special Issue The Interaction between Cell and Virus)
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28 pages, 3229 KiB  
Article
Establishment of Human-Induced Pluripotent Stem Cell-Derived Neurons—A Promising In Vitro Model for a Molecular Study of Rabies Virus and Host Interaction
by Thanathom Chailangkarn, Nathiphat Tanwattana, Thanakorn Jaemthaworn, Sira Sriswasdi, Nanchaya Wanasen, Sithichoke Tangphatsornruang, Kantinan Leetanasaksakul, Yuparat Jantraphakorn, Wanapinun Nawae, Penpicha Chankeeree, Porntippa Lekcharoensuk, Boonlert Lumlertdacha and Challika Kaewborisuth
Int. J. Mol. Sci. 2021, 22(21), 11986; https://doi.org/10.3390/ijms222111986 - 05 Nov 2021
Cited by 8 | Viewed by 3194
Abstract
Rabies is a deadly viral disease caused by the rabies virus (RABV), transmitted through a bite of an infected host, resulting in irreversible neurological symptoms and a 100% fatality rate in humans. Despite many aspects describing rabies neuropathogenesis, numerous hypotheses remain unanswered and [...] Read more.
Rabies is a deadly viral disease caused by the rabies virus (RABV), transmitted through a bite of an infected host, resulting in irreversible neurological symptoms and a 100% fatality rate in humans. Despite many aspects describing rabies neuropathogenesis, numerous hypotheses remain unanswered and concealed. Observations obtained from infected primary neurons or mouse brain samples are more relevant to human clinical rabies than permissive cell lines; however, limitations regarding the ethical issue and sample accessibility become a hurdle for discovering new insights into virus–host interplays. To better understand RABV pathogenesis in humans, we generated human-induced pluripotent stem cell (hiPSC)-derived neurons to offer the opportunity for an inimitable study of RABV infection at a molecular level in a pathologically relevant cell type. This study describes the characteristics and detailed proteomic changes of hiPSC-derived neurons in response to RABV infection using LC-MS/MS quantitative analysis. Gene ontology (GO) enrichment of differentially expressed proteins (DEPs) reveals temporal changes of proteins related to metabolic process, immune response, neurotransmitter transport/synaptic vesicle cycle, cytoskeleton organization, and cell stress response, demonstrating fundamental underlying mechanisms of neuropathogenesis in a time-course dependence. Lastly, we highlighted plausible functions of heat shock cognate protein 70 (HSC70 or HSPA8) that might play a pivotal role in regulating RABV replication and pathogenesis. Our findings acquired from this hiPSC-derived neuron platform help to define novel cellular mechanisms during RABV infection, which could be applicable to further studies to widen views of RABV-host interaction. Full article
(This article belongs to the Special Issue The Interaction between Cell and Virus)
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Review

Jump to: Research

20 pages, 1663 KiB  
Review
How Can We Prevent Mother-to-Child Transmission of HTLV-1?
by Kazuo Itabashi, Tokuo Miyazawa and Kaoru Uchimaru
Int. J. Mol. Sci. 2023, 24(8), 6961; https://doi.org/10.3390/ijms24086961 - 09 Apr 2023
Cited by 3 | Viewed by 3107
Abstract
The perception of human T-cell leukemia virus type 1 (HTlV-1) infection as a “silent disease” has recently given way to concern that its presence may be having a variety of effects. HTLV-1 is known to cause adult T-cell leukemia (ATL), an aggressive cancer [...] Read more.
The perception of human T-cell leukemia virus type 1 (HTlV-1) infection as a “silent disease” has recently given way to concern that its presence may be having a variety of effects. HTLV-1 is known to cause adult T-cell leukemia (ATL), an aggressive cancer of peripheral CD4 T cells; however, it is also responsible for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Most patients develop ATL as a result of HTLV-1 mother-to-child transmission. The primary route of mother-to-child transmission is through the mother’s milk. In the absence of effective drug therapy, total artificial nutrition such as exclusive formula feeding is a reliable means of preventing mother-to-child transmission after birth, except for a small percentage of prenatal infections. A recent study found that the rate of mother-to-child transmission with short-term breastfeeding (within 90 days) did not exceed that of total artificial nutrition. Because these preventive measures are in exchange for the benefits of breastfeeding, clinical applications of antiretroviral drugs and immunotherapy with vaccines and neutralizing antibodies are urgently needed. Full article
(This article belongs to the Special Issue The Interaction between Cell and Virus)
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27 pages, 3946 KiB  
Review
Roles of TGF-β1 in Viral Infection during Pregnancy: Research Update and Perspectives
by Quang Duy Trinh, Ngan Thi Kim Pham, Kazuhide Takada, Hiroshi Ushijima, Shihoko Komine-Aizawa and Satoshi Hayakawa
Int. J. Mol. Sci. 2023, 24(7), 6489; https://doi.org/10.3390/ijms24076489 - 30 Mar 2023
Cited by 1 | Viewed by 2146
Abstract
Transforming growth factor-beta 1 (TGF-β1) is a pleiotropic growth factor playing various roles in the human body including cell growth and development. More functions of TGF-β1 have been discovered, especially its roles in viral infection. TGF-β1 is abundant at the maternal–fetal interface during [...] Read more.
Transforming growth factor-beta 1 (TGF-β1) is a pleiotropic growth factor playing various roles in the human body including cell growth and development. More functions of TGF-β1 have been discovered, especially its roles in viral infection. TGF-β1 is abundant at the maternal–fetal interface during pregnancy and plays an important function in immune tolerance, an essential key factor for pregnancy success. It plays some critical roles in viral infection in pregnancy, such as its effects on the infection and replication of human cytomegalovirus in syncytiotrophoblasts. Interestingly, its role in the enhancement of Zika virus (ZIKV) infection and replication in first-trimester trophoblasts has recently been reported. The above up-to-date findings have opened one of the promising approaches to studying the mechanisms of viral infection during pregnancy with links to corresponding congenital syndromes. In this article, we review our current and recent advances in understanding the roles of TGF-β1 in viral infection. Our discussion focuses on viral infection during pregnancy, especially in the first trimester. We highlight the mutual roles of viral infection and TGF-β1 in specific contexts and possible functions of the Smad pathway in viral infection, with a special note on ZIKV infection. In addition, we discuss promising approaches to performing further studies on this topic. Full article
(This article belongs to the Special Issue The Interaction between Cell and Virus)
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16 pages, 4056 KiB  
Review
Multiple Roles of TRIM21 in Virus Infection
by Xue Li, Lin Yang, Si Chen, Jiawei Zheng, Huimin Zhang and Linzhu Ren
Int. J. Mol. Sci. 2023, 24(2), 1683; https://doi.org/10.3390/ijms24021683 - 14 Jan 2023
Cited by 5 | Viewed by 2751
Abstract
The tripartite motif protein 21 (TRIM21) belongs to the TRIM family, possessing an E3 ubiquitin ligase activity. Similar to other TRIMs, TRIM21 also contains three domains (named RBCC), including the Really Interesting New Gene (RING) domain, one or two B-Box domains (B-Box), and [...] Read more.
The tripartite motif protein 21 (TRIM21) belongs to the TRIM family, possessing an E3 ubiquitin ligase activity. Similar to other TRIMs, TRIM21 also contains three domains (named RBCC), including the Really Interesting New Gene (RING) domain, one or two B-Box domains (B-Box), and one PRY/SPRY domain. Notably, we found that the RING and B-Box domains are relatively more conservative than the PRY/SPRY domain, suggesting that TRIM21 of different species had similar functions. Recent results showed that TRIM21 participates in virus infection by directly interacting with viral proteins or modulating immune and inflammatory responses. TRIM21 also acts as a cytosol high-affinity antibody Fc receptor, binding to the antibody–virus complex and triggering an indirect antiviral antibody-dependent intracellular neutralization (ADIN). This paper focuses on the recent progress in the mechanism of TRIM21 during virus infection and the application prospects of TRIM21 on virus infection. Full article
(This article belongs to the Special Issue The Interaction between Cell and Virus)
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11 pages, 1152 KiB  
Review
Restriction of Flaviviruses by an Interferon-Stimulated Gene SHFL/C19orf66
by Youichi Suzuki and Takeshi Murakawa
Int. J. Mol. Sci. 2022, 23(20), 12619; https://doi.org/10.3390/ijms232012619 - 20 Oct 2022
Cited by 4 | Viewed by 2019
Abstract
Flaviviruses (the genus Flavivirus of the Flaviviridae family) include many arthropod-borne viruses, often causing life-threatening diseases in humans, such as hemorrhaging and encephalitis. Although the flaviviruses have a significant clinical impact, it has become apparent that flavivirus replication is restricted by cellular factors [...] Read more.
Flaviviruses (the genus Flavivirus of the Flaviviridae family) include many arthropod-borne viruses, often causing life-threatening diseases in humans, such as hemorrhaging and encephalitis. Although the flaviviruses have a significant clinical impact, it has become apparent that flavivirus replication is restricted by cellular factors induced by the interferon (IFN) response, which are called IFN-stimulated genes (ISGs). SHFL (shiftless antiviral inhibitor of ribosomal frameshifting) is a novel ISG that inhibits dengue virus (DENV), West Nile virus (WNV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV) infections. Interestingly, SHFL functions as a broad-spectrum antiviral factor exhibiting suppressive activity against various types of RNA and DNA viruses. In this review, we summarize the current understanding of the molecular mechanisms by which SHFL inhibits flavivirus infection and discuss the molecular basis of the inhibitory mechanism using a predicted tertiary structure of SHFL generated by the program AlphaFold2. Full article
(This article belongs to the Special Issue The Interaction between Cell and Virus)
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