Drosophila as a Model for Infectious Diseases
Abstract
:1. Introduction
2. Innate Immune Signaling Pathways and Pathogenic Proteins that Affect Them
2.1. Salmonellae Enterica: AvrA and NF-κB (IMD)/JNK Signaling
2.2. Aeromonas Salmonicida: AopP and NF-κB (Toll and IMD) Signaling
2.3. HTLV-1: Tax1 in NF-κB (IMD) Signaling
2.4. HIV: Vpu in NF-κB (Toll) Signaling
2.5. HIV: Nef in JNK Signaling
3. Pathogenic Proteins that Affect Phagocytosis and Apoptosis
3.1. Pseudomonas aeruginosa: ExoS in Phagocytosis
3.2. SARS-CoV-1: 3a and M in Apoptosis
3.3. HIV: Vpu in Apoptosis through JNK Signaling
3.4. EBV: BZLF1 and BRLF1 in Apoptosis and Cell Proliferation
4. Pathogenic Proteins that Affect Fundamental Cellular Processes and Developmental Signaling Pathways
4.1. Zika Virus: NS4A in Neural Stem Cell Survival and Proliferation
4.2. Zika Virus: NS4A in JAK-STAT and Notch Signaling
4.3. Bacillus Anthracis: LF and EF in Multiple Signaling Pathways and Cell Adhesion
4.4. Vibrio Cholerae: CtxA in Notch Signaling and Cell Adhesion
4.5. HCMV: Immediate-Early Genes in Cell Adhesion
4.6. Helicobacter Pylori: CagA in Multiple Signaling Pathways, Cytoskeletal Organization and Microbiome Composition
4.7. HPV: E6 in Cell Polarity and Epithelial-to-Mesenchymal Transition
4.8. HIV: Tat in Cytoskeleton Organization and Protein Translation
4.9. SV40: Large and Small T Antigens in Mitosis
5. Drosophila Studies to Identify New Therapeutic Targets to Combat Infectious Diseases
5.1. Influenza Virus: M2 in pH Regulation
5.2. Pseudomonas aeruginosa. gshA and gshB in Bacterial Stress Resistance and Biofilm Production
6. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Type | Pathogens | Pathogenic Proteins | Section | Biological Processes Affected | In vivo Functions of Pathogenic Proteins |
---|---|---|---|---|---|
Bacteria | Aeromonas salmonicida | AopP | Section 2.2 | NF-kB signaling | Blocks the nuclear translocation of NF-kB (Relish and DIF), inhibiting both IMD and Toll pathways. |
Section 2.2 | Apoptosis | Facilitates the cleavage of Caspase-3, inducing apoptosis. | |||
Bacteria | Bacillus anthracis | EF | Section 4.3 | Hedgehog signaling | Hyperactivates PKA through its adenyl cyclase activity, activating Hedgehog signaling. Genetically interacts with hedgehog. |
Section 4.3 | Notch signaling | Alters the subcellular localization of Delta ligands via affecting Rab11-dependent vesicle trafficking. Acts synergistically with LF protein. | |||
Section 4.3 | Cell-cell adhesion | Alters the subcellular localization of E-Cadherin by activation of Epac through its adenyl cyclase activity. | |||
LF | Section 4.4 | JNK signaling | Inhibits JNK signaling upstream of hep (JNKK) in the developing thorax. | ||
Section 4.4 | EGFR signaling | Inhibits EGFR signaling in the developing wing disc through unknown mechanisms. Genetically interacts with Dsor1 (MAPKKK). | |||
Section 4.4 | Notch signaling | Alters the subcellular localization of Delta ligand via affecting Sec15-dependent vesicle trafficking. Acts synergistically with EF protein. | |||
Section 4.4 | Cell-cell adhesion | Alters the subcellular localization of E-Cadherin. | |||
Bacteria | Helicobacter pylori | CagA | Section 4.6 | EGFR/Sevenless signaling | Activates EGFR signaling by mimicking the function of Dos (Gab-family protein) in a phosphorylation dependent manner through Corkscrew (SHP-2). |
Section 4.6 | Cytoskeletal organization | Causes over-activation and altered subcellular localization of Spaghetti squash (Myosin light chain) via Rho GTPase in a phosphorylation-dependent manner. | |||
Section 4.6 | JNK signaling and apoptosis | Activates JNK signaling upstream of Bsk (JNK), leading to increase in apoptosis. | |||
Section 4.6 | Tumor metastasis | Synergizes with an oncogenic form of Ras (RasV12) to facilitate the invasion of tumors formed in the eye. Genetically interacts with basolateral protein coding genes dlg1 and l(2)gl that function as tumor suppressors. | |||
Section 4.6 | Microbiome homeostasis | Causes dysbiosis of gastric microbiota when expressed in the digestive tract, leading to activation of immune responses in a phosphorylation-dependent manner. | |||
Bacteria | Pseudomonas aeruginosa | ExoS | Section 3.1 | Phagocytosis | Inhibits phagocytosis by blocking Rac2 (Rho family GTPase) function in hemocytes. |
gshA, gshB | Section 5.2 | Bacterial stress resistance and biofilm production | Protects bacteria from ROS while negatively regulating the formation of biofilms. | ||
Bacteria | Salmonellae enterica | AvrA | Section 2.1 | NF-kB signaling | Blocks the nuclear translocation of NF-kB (Relish) in an enzymatic activity-dependent manner, inhibiting the IMD pathway. |
Section 2.1 | JNK signaling | Decreases activity of MKK4 (JNKK), inhibiting JNK signaling. | |||
Bacteria | Vibrio cholerae | CtxA | Section 4.4 | Notch signaling | Alters the subcellular localization of Delta ligand via affecting Rab11-dependent vesicle trafficking in an adenyl cyclase activity-dependent manner. |
Section 4.4 | Cell-cell adhesion | Alters the subcellular localization of E-Cadherin by affecting Rab11-dependent vesicle trafficking. | |||
Virus | Epstein Barr virus (EBV) | BRLF1 | Section 3.4 | Cell proliferation | Promotes cell proliferation. Genetically interacts with p53, Tor, reaper, and other genes. |
BZLF1 | Section 3.4 | Apoptosis and cell proliferation | Works with shaven (Pax transcription factor) to facilitate apoptosis and inhibit cell proliferation. Genetically interacts with p53, Tor, reaper, and other genes. | ||
Virus | Influenza virus | M2 | Section 5.1 | pH homeostasis | Increases intracellular pH through its function as a proton channel. |
Virus | Human Cytomegalovirus (HCMV) | IE72, IE86 | Section 4.5 | Cell-cell adhesion | Alters the subcellular localization of Armadillo (b-Catenin). |
Virus | Human Immunodeficiency Virus (HIV) | Nef | Section 2.5 | JNK signaling and apoptosis | Activates JNK signaling, leading to an increase in apoptosis. Genetically interacts with bsk (JNK) and hep (JNKK). |
Tat | Section 4.8 | Cytoskeletal organization | Decreases the rate of Tubulin polymerization during cytoplasmic streaming during oogenesis and mitosis during early embryogenesis. | ||
Section 4.8 | Protein translation | Interferes with ribosome biosynthesis by binding to pre-rRNA and Fibrillarin. | |||
Vpu | Section 2.4 | NF-kB signaling | Inhibits Slmb (b-TRcP) in a phosphorylation-dependent manner, activating the Toll pathway. | ||
Section 3.3 | JNK signaling and apoptosis | Activates JNK signaling upstream of hep (JNKK) in a phosphorylation-independent manner, leading to an increase in apoptosis. | |||
Virus | Human papillomavirus (HPV) | E6 | Section 4.7 | Cell adhesion and polarity | Causes disruption of cell adhesion and polarity by degrading proteins such as Dlg1, Scrib, and Magi with Ube3A (E3 ligase) during wing development. |
Section 4.7 | Insulin signaling | Genetically interacts with a dominant-negative form of Insulin receptor during eye development. | |||
Section 4.7 | Epithelial-to-mesenchymal transition (EMT) | Genetically interacts with oncogenic forms of Ras and Notch to contribute to EMT. | |||
Virus | Human T Cell Lymphotropic Virus type 1 (HTLV-1) | Tax1 | Section 2.3 | NF-kB signaling | Inhibits Kenny (IKKg) in a Urmylation-dependent manner, activating the IMD pathway. |
Virus | Severe Acute Respiratory Syndrome Coronavirus-1 (SARS-CoV-1) | 3a | Section 3.2 | PKB/AKT signaling and apoptosis | Inhibits the Pdk1-Akt1 axis of the PKB/AKT pathway, leading to an increase in apoptosis. |
M | Section 3.2 | Apoptosis | Promotes apoptosis in an ion channel activity-dependent fashion. | ||
Virus | Simian vacuolating virus 40 (SV40) | Small T antigen | Section 4.9 | Mitosis | Causes mitotic spindle abnormalities by working with PP2A and upregulating Cyclin E expression. |
Virus | Zika virus (ZIKV) | NS4A | Section 4.1 | Asymmetric cell division | Inhibits Ball (Vrk1) to misregulate proper segregation of cell polarity regulators in neural stem cells. |
Section 4.1 | Apoptosis | Induces apoptosis in the nervous system. | |||
Section 4.2 | JAK-STAT signaling | Inhibits JAK-STAT signaling downstream of hopscotch (JAK kinase) in the developing wing. | |||
Section 4.2 | Notch signaling | Inhibits Notch signaling in the developing wing through unknown mechanisms. |
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Harnish, J.M.; Link, N.; Yamamoto, S. Drosophila as a Model for Infectious Diseases. Int. J. Mol. Sci. 2021, 22, 2724. https://doi.org/10.3390/ijms22052724
Harnish JM, Link N, Yamamoto S. Drosophila as a Model for Infectious Diseases. International Journal of Molecular Sciences. 2021; 22(5):2724. https://doi.org/10.3390/ijms22052724
Chicago/Turabian StyleHarnish, J. Michael, Nichole Link, and Shinya Yamamoto. 2021. "Drosophila as a Model for Infectious Diseases" International Journal of Molecular Sciences 22, no. 5: 2724. https://doi.org/10.3390/ijms22052724