-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing and Potentially Promotes Neoplasia
The oriental liver fluke Opisthorchis viverrini infects millions of people in SE-Asia and kills 26,000 people each year due to parasite-induced liver cancer. The mechanisms by which the parasite causes cancer are complex, but a role for excessive wound healing in response to feeding parasites in the bile ducts has been proposed. We show that a growth factor (granulin) secreted by the worm gets into bile duct cells and drives wound healing and blood vessel growth. We delve into this “supercharged” wound healing process and uncover a range of signaling molecules that initiate healing, but when dysregulated, can result in a deadly liver cancer. On the upside, this liver fluke growth factor is now a candidate drug for the development of novel wound healing therapeutics to treat chronic wounds, such as diabetic ulcers. Understanding this process is another step on the road to developing a vaccine to reduce both parasite burdens and the incidence of the most prevalent and fatal cancer in Thailand and surrounding countries.
Vyšlo v časopise: Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing and Potentially Promotes Neoplasia. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005209
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005209Souhrn
The oriental liver fluke Opisthorchis viverrini infects millions of people in SE-Asia and kills 26,000 people each year due to parasite-induced liver cancer. The mechanisms by which the parasite causes cancer are complex, but a role for excessive wound healing in response to feeding parasites in the bile ducts has been proposed. We show that a growth factor (granulin) secreted by the worm gets into bile duct cells and drives wound healing and blood vessel growth. We delve into this “supercharged” wound healing process and uncover a range of signaling molecules that initiate healing, but when dysregulated, can result in a deadly liver cancer. On the upside, this liver fluke growth factor is now a candidate drug for the development of novel wound healing therapeutics to treat chronic wounds, such as diabetic ulcers. Understanding this process is another step on the road to developing a vaccine to reduce both parasite burdens and the incidence of the most prevalent and fatal cancer in Thailand and surrounding countries.
Zdroje
1. Sripa B, Brindley PJ, Mulvenna J, Laha T, Smout MJ, Mairiang E, et al. The tumorigenic liver fluke Opisthorchis viverrini—multiple pathways to cancer. Trends Parasitol. 2012 Oct;28(10):395–407. doi: 10.1016/j.pt.2012.07.006 22947297
2. Smout MJ, Sripa B, Laha T, Mulvenna J, Gasser RB, Young ND, et al. Infection with the carcinogenic human liver fluke, Opisthorchis viverrini. Mol Biosyst. 2011 May;7(5):1367–1375. doi: 10.1039/c0mb00295j 21311794
3. Sripa B, Kaewkes S, Sithithaworn P, Mairiang E, Laha T, Smout M, et al. Liver fluke induces cholangiocarcinoma. PLoS Med. 2007 Jul;4(7):e201. 17622191
4. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005 Mar-Apr;55(2):74–108. 15761078
5. Sriamporn S, Pisani P, Pipitgool V, Suwanrungruang K, Kamsa-ard S, Parkin DM. Prevalence of Opisthorchis viverrini infection and incidence of cholangiocarcinoma in Khon Kaen, Northeast Thailand. Trop Med Int Health. 2004 May;9(5):588–594. 15117303
6. Mulvenna J, Sripa B, Brindley PJ, Gorman J, Jones MK, Colgrave ML, et al. The secreted and surface proteomes of the adult stage of the carcinogenic human liver fluke Opisthorchis viverrini. Proteomics. 2010 Mar;10(5):1063–1078. doi: 10.1002/pmic.200900393 20049860
7. Smout MJ, Laha T, Mulvenna J, Sripa B, Suttiprapa S, Jones A, et al. A granulin-like growth factor secreted by the carcinogenic liver fluke, Opisthorchis viverrini, promotes proliferation of host cells. PLoS Pathog. 2009 Oct;5(10):e1000611. doi: 10.1371/journal.ppat.1000611 19816559
8. Schafer M, Werner S. Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol. 2008 Aug;9(8):628–638. doi: 10.1038/nrm2455 18628784
9. De Muynck L, Van Damme P. Cellular effects of progranulin in health and disease. J Mol Neurosci. 2011 Nov;45(3):549–560. doi: 10.1007/s12031-011-9553-z 21611805
10. Zheng Y, Brady OA, Meng PS, Mao Y, Hu F. C-terminus of progranulin interacts with the beta-propeller region of sortilin to regulate progranulin trafficking. PLoS One. 2011 6(6):e21023. doi: 10.1371/journal.pone.0021023 21698296
11. Park B, Buti L, Lee S, Matsuwaki T, Spooner E, Brinkmann MM, et al. Granulin is a soluble cofactor for toll-like receptor 9 signaling. Immunity. 2011 Apr 22;34(4):505–513. doi: 10.1016/j.immuni.2011.01.018 21497117
12. Hoque M, Mathews MB, Pe'ery T. Progranulin (granulin/epithelin precursor) and its constituent granulin repeats repress transcription from cellular promoters. J Cell Physiol. 2010 Apr;223(1):224–233. doi: 10.1002/jcp.22031 20054825
13. Hu F, Padukkavidana T, Vaegter CB, Brady OA, Zheng Y, Mackenzie IR, et al. Sortilin-mediated endocytosis determines levels of the frontotemporal dementia protein, progranulin. Neuron. 2010 Nov 18;68(4):654–667. doi: 10.1016/j.neuron.2010.09.034 21092856
14. Ishibe T, Nakayama T, Okamoto T, Aoyama T, Nishijo K, Shibata KR, et al. Disruption of fibroblast growth factor signal pathway inhibits the growth of synovial sarcomas: potential application of signal inhibitors to molecular target therapy. Clin Cancer Res. 2005 Apr 1;11(7):2702–2712. 15814652
15. Olsnes S, Klingenberg O, Wiedlocha A. Transport of exogenous growth factors and cytokines to the cytosol and to the nucleus. Physiol Rev. 2003 Jan;83(1):163–182. 12506129
16. Papatpremsiri A, Smout MJ, Loukas A, Brindley PJ, Sripa B, Laha T. Suppression of Ov-grn-1 encoding granulin of Opisthorchis viverrini inhibits proliferation of biliary epithelial cells. Exp Parasitol. 2015 Jan;14817–23.
17. Liang CC, Park AY, Guan JL. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2007 2(2):329–333. 17406593
18. Reid RR, Said HK, Mogford JE, Mustoe TA. The future of wound healing: pursuing surgical models in transgenic and knockout mice. J Am Coll Surg. 2004 Oct;199(4):578–585. 15454143
19. Wong VW, Sorkin M, Glotzbach JP, Longaker MT, Gurtner GC. Surgical approaches to create murine models of human wound healing. J Biomed Biotechnol. 2011 Dec;2011(Dec 12): pii: 969618. doi: 969610.961155/962011/969618
20. Ribatti D. Chicken chorioallantoic membrane angiogenesis model. Methods Mol Biol. 2012 84347–57.
21. Chan LY, Gunasekera S, Henriques ST, Worth NF, Le SJ, Clark RJ, et al. Engineering pro-angiogenic peptides using stable, disulfide-rich cyclic scaffolds. Blood. 2011 Dec 15;118(25):6709–6717. doi: 10.1182/blood-2011-06-359141 22039263
22. Bateman A, Bennett HP. The granulin gene family: from cancer to dementia. Bioessays. 2009 Nov;31(11):1245–1254. doi: 10.1002/bies.200900086 19795409
23. Shalaby SY, Blume P, Sumpio BE. New modalities in the chronic ischemic diabetic foot management. Clin Podiatr Med Surg. 2014 Jan;31(1):27–42. doi: 10.1016/j.cpm.2013.09.009 24296016
24. Cenik B, Sephton CF, Kutluk Cenik B, Herz J, Yu G. Progranulin: a proteolytically processed protein at the crossroads of inflammation and neurodegeneration. J Biol Chem. 2012 Sep 21;287(39):32298–32306. 22859297
25. Gobel M, Eisele L, Mollmann M, Huttmann A, Johansson P, Scholtysik R, et al. Progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia. PLoS One. 2013 8(8):e72107. doi: 10.1371/journal.pone.0072107 24009671
26. Ho JC, Ip YC, Cheung ST, Lee YT, Chan KF, Wong SY, et al. Granulin-epithelin precursor as a therapeutic target for hepatocellular carcinoma. Hepatology. 2008 May;47(5):1524–1532. doi: 10.1002/hep.22191 18393387
27. Cheung PF, Yip CW, Wong NC, Fong DY, Ng LW, Wan AM, et al. Granulin-epithelin precursor renders hepatocellular carcinoma cells resistant to natural killer cytotoxicity. Cancer Immunol Res. 2014 Dec;2(12):1209–1219. doi: 10.1158/2326-6066.CIR-14-0096 25315249
28. Young ND, Nagarajan N, Lin SJ, Korhonen PK, Jex AR, Hall RS, et al. The Opisthorchis viverrini genome provides insights into life in the bile duct. Nat Commun. 2014 Oct 7;5(Oct): pii: 4378. doi: 4310.1038/ncomms5378
29. Tang W, Lu Y, Tian QY, Zhang Y, Guo FJ, Liu GY, et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science. 2011 Apr 22;332(6028):478–484. doi: 10.1126/science.1199214 21393509
30. Tribolet L, Cantacessi C, Pickering DA, Navarro S, Doolan DL, Trieu A, et al. Probing of a human proteome microarray with a recombinant pathogen protein reveals a novel mechanism by which hookworms suppress B-cell receptor signaling. J Infect Dis. 2015 Feb 1;211(3):416–425. doi: 10.1093/infdis/jiu451 25139017
31. Wojtuszkiewicz A, Assaraf YG, Maas MJ, Kaspers GJ, Jansen G, Cloos J. Pre-mRNA splicing in cancer: the relevance in oncogenesis, treatment and drug resistance. Expert Opin Drug Metab Toxicol. 2014 Dec 13;1–17. doi: 10.1517/17425255.2015.993316 25495223
32. Bebee TW, Cieply BW, Carstens RP. Genome-wide activities of RNA binding proteins that regulate cellular changes in the epithelial to mesenchymal transition (EMT). Adv Exp Med Biol. 2014 Oct 9;825(Oct):267–302.
33. Jensen MA, Wilkinson JE, Krainer AR. Splicing factor SRSF6 promotes hyperplasia of sensitized skin. Nat Struct Mol Biol. 2014 Feb;21(2):189–197. doi: 10.1038/nsmb.2756 24440982
34. Saitoh M, Miyazawa K. Transcriptional and post-transcriptional regulation in TGF-beta-mediated epithelial-mesenchymal transition. J Biochem. 2012 Jun;151(6):563–571. doi: 10.1093/jb/mvs040 22528665
35. Dehm SM. Test-firing ammunition for spliceosome inhibition in cancer. Clin Cancer Res. 2013 Nov 15;19(22):6064–6066. doi: 10.1158/1078-0432.CCR-13-2461 24097858
36. Raghuwanshi SK, Su Y, Singh V, Haynes K, Richmond A, Richardson RM. The chemokine receptors CXCR1 and CXCR2 couple to distinct G protein-coupled receptor kinases to mediate and regulate leukocyte functions. J Immunol. 2012 Sep 15;189(6):2824–2832. doi: 10.4049/jimmunol.1201114 22869904
37. Verbeke H, Geboes K, Van Damme J, Struyf S. The role of CXC chemokines in the transition of chronic inflammation to esophageal and gastric cancer. Biochim Biophys Acta. 2012 Jan;1825(1):117–129. doi: 10.1016/j.bbcan.2011.10.008 22079531
38. Bolitho C, Hahn MA, Baxter RC, Marsh DJ. The chemokine CXCL1 induces proliferation in epithelial ovarian cancer cells by transactivation of the epidermal growth factor receptor. Endocr Relat Cancer. 2010 Dec;17(4):929–940. doi: 10.1677/ERC-10-0107 20702723
39. Russo RC, Garcia CC, Teixeira MM, Amaral FA. The CXCL8/IL-8 chemokine family and its receptors in inflammatory diseases. Expert Rev Clin Immunol. 2014 May;10(5):593–619. doi: 10.1586/1744666X.2014.894886 24678812
40. Semple BD, Kossmann T, Morganti-Kossmann MC. Role of chemokines in CNS health and pathology: a focus on the CCL2/CCR2 and CXCL8/CXCR2 networks. J Cereb Blood Flow Metab. 2010 Mar;30(3):459–473. doi: 10.1038/jcbfm.2009.240 19904283
41. Danen EH. Ignoring matrix boundaries when the LKB1 master kinase is gone. J Cell Biol. 2014 Oct 27;207(2):167–169. doi: 10.1083/jcb.201409107 25349256
42. Ringwood L, Li L. The involvement of the interleukin-1 receptor-associated kinases (IRAKs) in cellular signaling networks controlling inflammation. Cytokine. 2008 Apr;42(1):1–7. doi: 10.1016/j.cyto.2007.12.012 18249132
43. Sanchez-Cespedes M. A role for LKB1 gene in human cancer beyond the Peutz-Jeghers syndrome. Oncogene. 2007 Dec 13;26(57):7825–7832. 17599048
44. Yang D, Chen W, Xiong J, Sherrod CJ, Henry DH, Dittmer DP. Interleukin 1 receptor-associated kinase 1 (IRAK1) mutation is a common, essential driver for Kaposi sarcoma herpesvirus lymphoma. PNAS. 2014 Nov 4;111(44):E4762–4768. doi: 10.1073/pnas.1405423111 25341731
45. Morgan C, Nigam Y. Naturally derived factors and their role in the promotion of angiogenesis for the healing of chronic wounds. Angiogenesis. 2013 Jul;16(3):493–502. doi: 10.1007/s10456-013-9341-1 23417553
46. Wei F, Zhang Y, Zhao W, Yu X, Liu CJ. Progranulin facilitates conversion and function of regulatory T cells under inflammatory conditions. PLoS One. 2014 9(11):e112110. doi: 10.1371/journal.pone.0112110 25393765
47. Wilson MS, Taylor MD, Balic A, Finney CA, Lamb JR, Maizels RM. Suppression of allergic airway inflammation by helminth-induced regulatory T cells. J Exp Med. 2005 Nov 7;202(9):1199–1212. 16275759
48. Croese J, Giacomin P, Navarro S, Clouston A, McCann L, Dougall A, et al. Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease. J Allergy Clin Immunol. 2015 Feb;135(2):508–516. doi: 10.1016/j.jaci.2014.07.022 25248819
49. Wammes LJ, Mpairwe H, Elliott AM, Yazdanbakhsh M. Helminth therapy or elimination: epidemiological, immunological, and clinical considerations. Lancet Infect Dis. 2014 Nov;14(11):1150–1162. doi: 10.1016/S1473-3099(14)70771-6 24981042
50. Sripa B, Kaewkes S. Localisation of parasite antigens and inflammatory responses in experimental opisthorchiasis. Int J Parasitol. 2000 May;30(6):735–740. 10856508
51. Studier FW. Protein production by auto-induction in high density shaking cultures. Protein Expr Purif. 2005 May;41(1):207–234. 15915565
52. Smout MJ, Mulvenna JP, Jones MK, Loukas A. Expression, refolding and purification of Ov-GRN-1, a granulin-like growth factor from the carcinogenic liver fluke, that causes proliferation of mammalian host cells. Protein Expr Purif. 2011 Oct;79(2):263–270. doi: 10.1016/j.pep.2011.06.018 21757010
53. Grubman SA, Perrone RD, Lee DW, Murray SL, Rogers LC, Wolkoff LI, et al. Regulation of intracellular pH by immortalized human intrahepatic biliary epithelial cell lines. Am J Physiol. 1994 Jun;266(6 Pt 1):G1060–1070. 8023938
54. Matsumura T, Takesue M, Westerman KA, Okitsu T, Sakaguchi M, Fukazawa T, et al. Establishment of an immortalized human-liver endothelial cell line with SV40T and hTERT. Transplantation. 2004 May 15;77(9):1357–1365. 15167590
55. Tepsiri N, Chaturat L, Sripa B, Namwat W, Wongkham S, Bhudhisawasdi V, et al. Drug sensitivity and drug resistance profiles of human intrahepatic cholangiocarcinoma cell lines. World J Gastroenterol. 2005 May 14;11(18):2748–2753. 15884115
56. Xing JZ, Zhu L, Jackson JA, Gabos S, Sun XJ, Wang XB, et al. Dynamic monitoring of cytotoxicity on microelectronic sensors. Chem Res Toxicol. 2005 Feb;18(2):154–161. 15720119
57. Invitrogen. Alexa Fluor 488 Protein Labeling Kit. 2006. Leiden: Molecular Probes.
58. Strauss MP, Liew AT, Turnbull L, Whitchurch CB, Monahan LG, Harry EJ. 3D-SIM super resolution microscopy reveals a bead-like arrangement for FtsZ and the division machinery: implications for triggering cytokinesis. PLoS Biol. 2012 10(9):e1001389. doi: 10.1371/journal.pbio.1001389 22984350
59. Schermelleh L, Carlton PM, Haase S, Shao L, Winoto L, Kner P, et al. Subdiffraction multicolor imaging of the nuclear periphery with 3D structured illumination microscopy. Science. 2008 Jun 6;320(5881):1332–1336. doi: 10.1126/science.1156947 18535242
60. Ribatti D. Chick embryo chorioallantoic membrane as a useful tool to study angiogenesis. Int Rev Cell Mol Biol. 2008 270181–224.
61. Mulvenna J, Hamilton B, Nagaraj SH, Smyth D, Loukas A, Gorman JJ. Proteomics analysis of the excretory/secretory component of the blood-feeding stage of the hookworm, Ancylostoma caninum. Mol Cell Proteomics. 2009 Jan;8(1):109–121. doi: 10.1074/mcp.M800206-MCP200 18753127
62. Aggarwal K, Choe LH, Lee KH. Shotgun proteomics using the iTRAQ isobaric tags. Brief Funct Genomic Proteomic. 2006 Jun;5(2):112–120. 16772272
63. Prasopdee S, Tesana S, Cantacessi C, Laha T, Mulvenna J, Grams R, et al. Proteomic profile of Bithynia siamensis goniomphalos snails upon infection with the carcinogenic liver fluke Opisthorchis viverrini. J Proteomics. 2015 Jan 15;113281–291.
64. Sotillo J, Sanchez-Flores A, Cantacessi C, Harcus Y, Pickering D, Bouchery T, et al. Secreted proteomes of different developmental stages of the gastrointestinal nematode Nippostrongylus brasiliensis. Mol Cell Proteomics. 2014 Oct;13(10):2736–2751. doi: 10.1074/mcp.M114.038950 24994561
65. Searle BC. Scaffold: a bioinformatic tool for validating MS/MS-based proteomic studies. Proteomics. 2010 Mar;10(6):1265–1269. doi: 10.1002/pmic.200900437 20077414
66. Keller A, Nesvizhskii AI, Kolker E, Aebersold R. Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. Anal Chem. 2002 Oct 15;74(20):5383–5392. 12403597
67. Nesvizhskii AI, Keller A, Kolker E, Aebersold R. A statistical model for identifying proteins by tandem mass spectrometry. Anal Chem. 2003 Sep 1;75(17):4646–4658. 14632076
68. Shadforth IP, Dunkley TP, Lilley KS, Bessant C. i-Tracker: for quantitative proteomics using iTRAQ. BMC Genomics. 2005 Oct 26;6(Oct): pii: 145. doi: 110.1186/1471-2164-1186-1145
69. Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, et al. STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 2013 Jan;41(Database issue):D808–815. doi: 10.1093/nar/gks1094 23203871
70. Sripa J, Pinlaor P, Brindley PJ, Sripa B, Kaewkes S, Robinson MW, et al. RNA interference targeting cathepsin B of the carcinogenic liver fluke, Opisthorchis viverrini. Parasitol Int. 2011 Sep;60(3):283–288. doi: 10.1016/j.parint.2011.04.003 21565281
71. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008 Jun 5;3(6):1101–1108. 18546601
Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium
Článek TRIM21 Promotes cGAS and RIG-I Sensing of Viral Genomes during Infection by Antibody-Opsonized VirusČlánek Effector OspB Activates mTORC1 in a Manner That Depends on IQGAP1 and Promotes Cell ProliferationČlánek Fundamental Roles of the Golgi-Associated Aspartyl Protease, ASP5, at the Host-Parasite InterfaceČlánek Modulation of the Surface Proteome through Multiple Ubiquitylation Pathways in African Trypanosomes
Článok vyšiel v časopisePLOS Pathogens
Najčítanejšie tento týždeň
2015 Číslo 10- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
-
Všetky články tohto čísla
- Expression of Concern: Misregulation of Underlies the Developmental Abnormalities Caused by Three Distinct Viral Silencing Suppressors in Arabidopsis
- Preparing for the Next Epidemic with Basic Virology
- Effectively Communicating the Uncertainties Surrounding Ebola Virus Transmission
- Translating Basic Research into Clinical Applications: Malaria Research at an NIH Lab
- A Gut Odyssey: The Impact of the Microbiota on Spore Formation and Germination
- Papillomavirus E6 Oncoproteins Take Common Structural Approaches to Solve Different Biological Problems
- Chronobiomics: The Biological Clock as a New Principle in Host–Microbial Interactions
- Dimensions of Horizontal Gene Transfer in Eukaryotic Microbial Pathogens
- Addressing the Complications of Ebola and Other Viral Hemorrhagic Fever Infections: Using Insights from Bacterial and Fungal Sepsis
- Time for Chocolate: Current Understanding and New Perspectives on Cacao Witches’ Broom Disease Research
- Ganglioside and Non-ganglioside Mediated Host Responses to the Mouse Polyomavirus
- Crosslinking of a Peritrophic Matrix Protein Protects Gut Epithelia from Bacterial Exotoxins
- Structure Elucidation of Coxsackievirus A16 in Complex with GPP3 Informs a Systematic Review of Highly Potent Capsid Binders to Enteroviruses
- CD39 Expression Identifies Terminally Exhausted CD8 T Cells
- Abiotic Stresses Antagonize the Rice Defence Pathway through the Tyrosine-Dephosphorylation of OsMPK6
- Dissociation of Tissue Destruction and Bacterial Expansion during Bubonic Plague
- Interferon-γ: The Jekyll and Hyde of Malaria
- CCR2 Inflammatory Dendritic Cells and Translocation of Antigen by Type III Secretion Are Required for the Exceptionally Large CD8 T Cell Response to the Protective YopE Epitope during Infection
- A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1
- The Suramin Derivative NF449 Interacts with the 5-fold Vertex of the Enterovirus A71 Capsid to Prevent Virus Attachment to PSGL-1 and Heparan Sulfate
- Trans-generational Immune Priming Protects the Eggs Only against Gram-Positive Bacteria in the Mealworm Beetle
- Peripheral Vγ9Vδ2 T Cells Are a Novel Reservoir of Latent HIV Infection
- Respiratory Syncytial Virus Disease Is Mediated by Age-Variable IL-33
- TRIM21 Promotes cGAS and RIG-I Sensing of Viral Genomes during Infection by Antibody-Opsonized Virus
- Modeling the Effects of Vorinostat Reveals both Transient and Delayed HIV Transcriptional Activation and Minimal Killing of Latently Infected Cells
- Identification of a Novel Lipoprotein Regulator of Spore Germination
- Calcium Regulation of Hemorrhagic Fever Virus Budding: Mechanistic Implications for Host-Oriented Therapeutic Intervention
- Antigen-Specific Th17 Cells Are Primed by Distinct and Complementary Dendritic Cell Subsets in Oropharyngeal Candidiasis
- Comparative Life Cycle Transcriptomics Revises Genome Annotation and Links a Chromosome Duplication with Parasitism of Vertebrates
- The Autophagy Receptor TAX1BP1 and the Molecular Motor Myosin VI Are Required for Clearance of Salmonella Typhimurium by Autophagy
- Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing and Potentially Promotes Neoplasia
- Effector OspB Activates mTORC1 in a Manner That Depends on IQGAP1 and Promotes Cell Proliferation
- Dengue Virus Infection of Requires a Putative Cysteine Rich Venom Protein
- Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma
- Fundamental Roles of the Golgi-Associated Aspartyl Protease, ASP5, at the Host-Parasite Interface
- Phenotypic and Functional Alterations in Circulating Memory CD8 T Cells with Time after Primary Infection
- Systematic Identification of Cyclic-di-GMP Binding Proteins in Reveals a Novel Class of Cyclic-di-GMP-Binding ATPases Associated with Type II Secretion Systems
- Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses
- Myeloid Cell Arg1 Inhibits Control of Arthritogenic Alphavirus Infection by Suppressing Antiviral T Cells
- The White-Nose Syndrome Transcriptome: Activation of Anti-fungal Host Responses in Wing Tissue of Hibernating Little Brown Myotis
- Influenza Virus Reassortment Is Enhanced by Semi-infectious Particles but Can Be Suppressed by Defective Interfering Particles
- Identification of the Mechanisms Causing Reversion to Virulence in an Attenuated SARS-CoV for the Design of a Genetically Stable Vaccine
- Differentiation-Dependent KLF4 Expression Promotes Lytic Epstein-Barr Virus Infection in Epithelial Cells
- The Histone Acetyltransferase Hat1 Regulates Stress Resistance and Virulence via Distinct Chromatin Assembly Pathways
- C-di-GMP Regulates Motile to Sessile Transition by Modulating MshA Pili Biogenesis and Near-Surface Motility Behavior in
- Modulation of the Surface Proteome through Multiple Ubiquitylation Pathways in African Trypanosomes
- Crystal Structure of the Human Cytomegalovirus Glycoprotein B
- Depletion of . GlmU from Infected Murine Lungs Effects the Clearance of the Pathogen
- Immunologic Control of Papillomavirus Type 1
- Requires Host Rab1b for Survival in Macrophages
- Structure Analysis Uncovers a Highly Diverse but Structurally Conserved Effector Family in Phytopathogenic Fungi
- PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8 T Cell Killing
- Phospho-dependent Regulation of SAMHD1 Oligomerisation Couples Catalysis and Restriction
- IL-4 Induced Innate CD8 T Cells Control Persistent Viral Infection
- Crystal Structures of a Piscine Betanodavirus: Mechanisms of Capsid Assembly and Viral Infection
- BCG Skin Infection Triggers IL-1R-MyD88-Dependent Migration of EpCAM CD11b Skin Dendritic cells to Draining Lymph Node During CD4+ T-Cell Priming
- Antigenic Characterization of the HCMV gH/gL/gO and Pentamer Cell Entry Complexes Reveals Binding Sites for Potently Neutralizing Human Antibodies
- Rescue of a Plant Negative-Strand RNA Virus from Cloned cDNA: Insights into Enveloped Plant Virus Movement and Morphogenesis
- Geminivirus Activates to Accelerate Cytoplasmic DCP2-Mediated mRNA Turnover and Weakens RNA Silencing in
- Disruption of Sphingolipid Biosynthesis Blocks Phagocytosis of
- The Fungal Exopolysaccharide Galactosaminogalactan Mediates Virulence by Enhancing Resistance to Neutrophil Extracellular Traps
- The Timing of Stimulation and IL-2 Signaling Regulate Secondary CD8 T Cell Responses
- Structural and Functional Analysis of Murine Polyomavirus Capsid Proteins Establish the Determinants of Ligand Recognition and Pathogenicity
- The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion
- PLOS Pathogens
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- Chronobiomics: The Biological Clock as a New Principle in Host–Microbial Interactions
- Interferon-γ: The Jekyll and Hyde of Malaria
- Crosslinking of a Peritrophic Matrix Protein Protects Gut Epithelia from Bacterial Exotoxins
- Antigen-Specific Th17 Cells Are Primed by Distinct and Complementary Dendritic Cell Subsets in Oropharyngeal Candidiasis
Prihlásenie#ADS_BOTTOM_SCRIPTS#Zabudnuté hesloZadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
- Časopisy