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Molecular Biology of Host and Pathogen Interactions: 2nd Edition

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

Deadline for manuscript submissions: 20 March 2025 | Viewed by 6629

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Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), 1349-008 Lisbon, Portugal
Interests: biological sciences; health sciences; infectious diseases; malaria; parasite–host interactions
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Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue, titled “Molecular Biology of Host and Pathogen Interactions”.

Any living being is constantly exposed to microorganisms and most have no effects on their health, with diseases being the exception and not the rule. However, when a host–microorganism interaction results in damage to the host, the microorganism becomes a pathogen with implications for both human and animal health.

Microorganisms such as bacteria, fungi, viruses, or parasites sustain themselves within host cells or organs on a molecular and cellular level and establish molecular mechanisms to invade, proliferate, and exploit cells for their survival. The understanding of these interactions is vital to the identification of biomarkers for diagnosis or individualized therapy of infections and is desirably driven by several independent areas of research such as molecular biology, biochemistry, immunology, cell biology, and all the omics.

The aim of this Special Issue is to highlight processes and mechanisms involved in the crosstalk between infectious agents and their hosts that may contribute at a later stage to the design of novel treatment or prevention strategies in the continuous fight against infectious diseases. We invite you to submit research articles, reviews, or short communications that together may contribute to improving the knowledge about this growing area of research.

Dr. Ana Paula Arez
Guest Editor

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Keywords

  • microbe
  • pathogen
  • virus
  • bacteria
  • parasite
  • fungi
  • infection
  • disease
  • interaction
  • host response

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Published Papers (6 papers)

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Research

15 pages, 2916 KiB  
Article
Expression of Network Medicine-Predicted Genes in Human Macrophages Infected with Leishmania major
by Felipe Caixeta, Vinicius Dantas Martins, Amanda Braga Figueiredo, Luis Carlos Crocco Afonso, Paolo Tieri, Filippo Castiglione, Leandro Martins de Freitas and Tatiani Uceli Maioli
Int. J. Mol. Sci. 2024, 25(22), 12084; https://doi.org/10.3390/ijms252212084 - 11 Nov 2024
Viewed by 456
Abstract
Leishmania spp. commonly infects phagocytic cells of the immune system, particularly macrophages, employing various immune evasion strategies that enable their survival by altering the intracellular environment. In mammals, these parasites establish persistent infections by modulating gene expression in macrophages, thus interfering with immune [...] Read more.
Leishmania spp. commonly infects phagocytic cells of the immune system, particularly macrophages, employing various immune evasion strategies that enable their survival by altering the intracellular environment. In mammals, these parasites establish persistent infections by modulating gene expression in macrophages, thus interfering with immune signaling and response pathways, ultimately creating a favorable environment for the parasite’s survival and reproduction. In this study, our objective was to use data mining and subsequent filtering techniques to identify the genes that play a crucial role in the infection process of Leishmania spp. We aimed to pinpoint genes that have the potential to influence the progression of Leishmania infection. To achieve this, we exploited prior, curated knowledge from major databases and constructed 16 datasets of human molecular information consisting of coding genes and corresponding proteins. We obtained over 400 proteins, identifying approximately 200 genes. The proteins coded by these genes were subsequently used to build a network of protein–protein interactions, which enabled the identification of key players; we named this set Predicted Genes. Then, we selected approximately 10% of Predicted Genes for biological validation. THP-1 cells, a line of human macrophages, were infected with Leishmania major in vitro for the validation process. We observed that L. major has the capacity to impact crucial genes involved in the immune response, resulting in macrophage inactivation and creating a conducive environment for the survival of Leishmania parasites. Full article
(This article belongs to the Special Issue Molecular Biology of Host and Pathogen Interactions: 2nd Edition)
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19 pages, 15116 KiB  
Article
Analysis of GCRV Pathogenesis and Therapeutic Measures Through Proteomic and Metabolomic Investigations in GCRV-Infected Tissues of Grass Carp (Ctenopharyngodon idella)
by Juhong Xie, Zhihui Jia, Yangyang Li, Lanjie Liao, Zuoyan Zhu, Yaping Wang and Rong Huang
Int. J. Mol. Sci. 2024, 25(21), 11852; https://doi.org/10.3390/ijms252111852 - 4 Nov 2024
Viewed by 607
Abstract
Hemorrhagic disease caused by grass carp reovirus (GCRV) infection is a major problem affecting the grass carp aquaculture industry. Therefore, inhibiting the spread of GCRV infection is of great economic significance. Herein, we sequenced five tissues (gill, liver, intestine, kidney, and muscle) from [...] Read more.
Hemorrhagic disease caused by grass carp reovirus (GCRV) infection is a major problem affecting the grass carp aquaculture industry. Therefore, inhibiting the spread of GCRV infection is of great economic significance. Herein, we sequenced five tissues (gill, liver, intestine, kidney, and muscle) from grass carp before and after GCRV infection using data-independent acquisition proteomic and untargeted metabolomic technologies, and quantitatively identified 10,808 proteins and 4040 metabolites. Then, we analyzed the differentially expressed proteins (DEPs) and metabolites (DEMs) before and after GCRV infection in the five tissues. Gene ontology analysis revealed that the five tissue DEPs were enriched in metabolic, including carbohydrate and lipid metabolic processes. Chemical taxonomy analysis showed that the categories of DEMs mainly included carbohydrates and lipids, such as fatty acids, glycerophospholipids, steroids, and their derivatives. Both the proteomic and the metabolomic data showed that GCRV affected the carbohydrate and lipid metabolism in the host. Shared pathway analysis was performed at both the protein and metabolic levels, showing significant enrichment of the glycolysis and pentose phosphate pathways (p < 0.001). Further analysis of glycolysis and pentose phosphate pathway inhibitors revealed that these two pathways are important for GCRV replication. As the kidney was the most affected among the five tissues, we analyzed the butanoate metabolism in the kidney, which revealed that most of the differentially expressed proteins and differently expressed metabolites in the butanoate metabolism were related to the TCA cycle. Further investigation showed that fumaric acid, an intermediate product in the TCA cycle, significantly inhibited GCRV replication in the CIK cells (p < 0.001), and that this inhibitory effect may be related to its induction of interferon system activation. The addition of fumaric acid to feed increased the survival rate of juvenile grass carp by 19.60% during GCRV infection, and protected the tissues of those infected with GCRV, making it a potential anti-GCRV feed additive. Our results provide new perspectives on GCRV pathogenesis and antiviral strategies for grass carp. Full article
(This article belongs to the Special Issue Molecular Biology of Host and Pathogen Interactions: 2nd Edition)
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14 pages, 3138 KiB  
Article
Whole Genome Identification and Biochemical Characteristics of the Tilletia horrida Cytochrome P450 Gene Family
by Yafei Wang, Yan Shi, Honglian Li, Senbo Wang and Aijun Wang
Int. J. Mol. Sci. 2024, 25(19), 10478; https://doi.org/10.3390/ijms251910478 - 28 Sep 2024
Viewed by 911
Abstract
Rice kernel smut caused by the biotrophic basidiomycete fungus Tilletia horrida causes significant yield losses in hybrid rice-growing areas around the world. Cytochrome P450 (CYP) enzyme is a membrane-bound heme-containing monooxygenase. In fungi, CYPs play a role in cellular metabolism, adaptation, pathogenicity, decomposition, [...] Read more.
Rice kernel smut caused by the biotrophic basidiomycete fungus Tilletia horrida causes significant yield losses in hybrid rice-growing areas around the world. Cytochrome P450 (CYP) enzyme is a membrane-bound heme-containing monooxygenase. In fungi, CYPs play a role in cellular metabolism, adaptation, pathogenicity, decomposition, and biotransformation of hazardous chemicals. In this study, we identified 20 CYP genes based on complete sequence analysis and functional annotation from the T. horrida JY-521 genome. The subcellular localization, conserved motifs, and structures of these 20 CYP genes were further predicted. The ThCYP genes exhibit differences in gene structures and protein motifs. Subcellular localization showed that they were located in the plasma membrane, cytoplasm, nucleus, mitochondria, and extracellular space, indicating that they had multiple functions. Some cis-regulatory elements related to stress response and plant hormones were found in the promoter regions of these genes. Protein–protein interaction (PPI) analysis showed that several ThCYP proteins interact with multiple proteins involved in the ergosterol pathway. Moreover, the expression of 20 CYP genes had different responses to different infection time points and underwent dynamic changes during T. horrida JY-521 infection, indicating that these genes were involved in the interaction with rice and their potential role in the pathogenic mechanism. These results provided valuable resources for elucidating the structure of T. horrida CYP family proteins and laid an important foundation for further research of their roles in the pathogenesis. Full article
(This article belongs to the Special Issue Molecular Biology of Host and Pathogen Interactions: 2nd Edition)
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22 pages, 2795 KiB  
Article
Computational Screening to Predict MicroRNA Targets in the Flavivirus 3′ UTR Genome: An Approach for Antiviral Development
by Rodolfo Gamaliel Avila-Bonilla and Juan Santiago Salas-Benito
Int. J. Mol. Sci. 2024, 25(18), 10135; https://doi.org/10.3390/ijms251810135 - 21 Sep 2024
Viewed by 769
Abstract
MicroRNAs (miRNAs) are molecules that influence messenger RNA (mRNA) expression levels by binding to the 3′ untranslated region (3′ UTR) of target genes. Host miRNAs can influence flavivirus replication, either by inducing changes in the host transcriptome or by directly binding to viral [...] Read more.
MicroRNAs (miRNAs) are molecules that influence messenger RNA (mRNA) expression levels by binding to the 3′ untranslated region (3′ UTR) of target genes. Host miRNAs can influence flavivirus replication, either by inducing changes in the host transcriptome or by directly binding to viral genomes. The 3′ UTR of the flavivirus genome is a conserved region crucial for viral replication. Cells might exploit this well-preserved region by generating miRNAs that interact with it, ultimately impacting viral replication. Despite significant efforts to identify miRNAs capable of arresting viral replication, the potential of all these miRNAs to interact with the flavivirus 3′ UTR is still poorly characterised. In this context, bioinformatic tools have been proposed as a fundamental part of accelerating the discovery of interactions between miRNAs and the 3′ UTR of viral genomes. In this study, we performed a computational analysis to reveal potential miRNAs from human and mosquito species that bind to the 3′ UTR of flaviviruses. In humans, miR-6842 and miR-661 were found, while in mosquitoes, miR-9-C, miR-2945-5p, miR-11924, miR-282-5p, and miR-79 were identified. These findings open new avenues for studying these miRNAs as antivirals against flavivirus infections. Full article
(This article belongs to the Special Issue Molecular Biology of Host and Pathogen Interactions: 2nd Edition)
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13 pages, 9306 KiB  
Article
Robust CXCL10/IP-10 and CCL5/RANTES Production Induced by Tick-Borne Encephalitis Virus in Human Brain Pericytes Despite Weak Infection
by Veronika Prančlová, Václav Hönig, Marta Zemanová, Daniel Růžek and Martin Palus
Int. J. Mol. Sci. 2024, 25(14), 7892; https://doi.org/10.3390/ijms25147892 - 18 Jul 2024
Viewed by 1209
Abstract
Tick-borne encephalitis virus (TBEV) targets the central nervous system (CNS), leading to potentially severe neurological complications. The neurovascular unit plays a fundamental role in the CNS and in the neuroinvasion of TBEV. However, the role of human brain pericytes, a key component of [...] Read more.
Tick-borne encephalitis virus (TBEV) targets the central nervous system (CNS), leading to potentially severe neurological complications. The neurovascular unit plays a fundamental role in the CNS and in the neuroinvasion of TBEV. However, the role of human brain pericytes, a key component of the neurovascular unit, during TBEV infection has not yet been elucidated. In this study, TBEV infection of the primary human brain perivascular pericytes was investigated with highly virulent Hypr strain and mildly virulent Neudoerfl strain. We used Luminex assay to measure cytokines/chemokines and growth factors. Both viral strains showed comparable replication kinetics, peaking at 3 days post infection (dpi). Intracellular viral RNA copies peaked at 6 dpi for Hypr and 3 dpi for Neudoerfl cultures. According to immunofluorescence staining, only small proportion of pericytes were infected (3% for Hypr and 2% for Neudoerfl), and no cytopathic effect was observed in the infected cells. In cell culture supernatants, IL-6 production was detected at 3 dpi, together with slight increases in IL-15 and IL-4, but IP-10, RANTES and MCP-1 were the main chemokines released after TBEV infection. These chemokines play key roles in both immune defense and immunopathology during TBE. This study suggests that pericytes are an important source of these signaling molecules during TBEV infection in the brain. Full article
(This article belongs to the Special Issue Molecular Biology of Host and Pathogen Interactions: 2nd Edition)
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17 pages, 8915 KiB  
Article
Rabies Virus Infection Causes Pyroptosis of Neuronal Cells
by Dongling Yu, Rong Jin, Jundan Liu, Chuanliang Zhang, Chenxing Duan, Xi Luo, Wenhao Yang, Cheng Liu, Jingjing Liang, Xiaoning Li and Tingrong Luo
Int. J. Mol. Sci. 2024, 25(11), 5616; https://doi.org/10.3390/ijms25115616 - 22 May 2024
Viewed by 1839
Abstract
Rabies virus (RABV) is a neurotropic virus that causes fatal neurological disease, raising serious public health issues and attracting extensive attention in society. To elucidate the molecular mechanism of RABV-induced neuronal damage, we used hematoxylin–eosin staining, transmission electron microscopy, transcriptomics analysis, and immune [...] Read more.
Rabies virus (RABV) is a neurotropic virus that causes fatal neurological disease, raising serious public health issues and attracting extensive attention in society. To elucidate the molecular mechanism of RABV-induced neuronal damage, we used hematoxylin–eosin staining, transmission electron microscopy, transcriptomics analysis, and immune response factor testing to investigate RABV-infected neurons. We successfully isolated the neurons from murine brains. The specificity of the isolated neurons was identified by a monoclonal antibody, and the viability of the neurons was 83.53–95.0%. We confirmed that RABV infection induced serious damage to the neurons according to histochemistry and transmission electron microscope (TEM) scanning. In addition, the transcriptomics analysis suggested that multiple genes related to the pyroptosis pathway were significantly upregulated, including gasdermin D (Gsdmd), Nlrp3, caspase-1, and IL-1β, as well as the chemokine genes Ccl2, Ccl3, Ccl4, Ccl5, Ccl7, Ccl12, and Cxcl10. We next verified this finding in the brains of mice infected with the rRC-HL, GX074, and challenge virus standard strain-24 (CVS-24) strains of RABV. Importantly, we found that the expression level of the Gsdmd protein was significantly upregulated in the neurons infected with different RABV strains and ranged from 691.1 to 5764.96 pg/mL, while the basal level of mock-infected neurons was less than 100 pg/mL. Taken together, our findings suggest that Gsdmd-induced pyroptosis is involved in the neuron damage caused by RABV infection. Full article
(This article belongs to the Special Issue Molecular Biology of Host and Pathogen Interactions: 2nd Edition)
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