-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
Evidence for a Novel Mechanism of Influenza Virus-Induced Type I Interferon Expression by a Defective RNA-Encoded Protein
Error-prone polymerase function of RNA viruses can result in expression of defective RNAs harboring internal deletions of various sizes. Small subgenomic RNAs are strong inducers of the antiviral response by serving as pathogen-associated patterns that are predominantly detected by cellular sensors. Recently, it has been shown that influenza A virus defective RNAs are not only generated upon passages in cell culture, but also in infected humans, indicating that these subgenomic RNAs may also be relevant in infections in vivo. Here, we characterize a novel defective RNA derived from the PB2 segment of a highly pathogenic H5N1 influenza A virus. This RNA encodes a 10 kDa peptide (PB2Δ) which activates type I interferon (IFN) responses through direct interaction with the adapter protein MAVS, a key component of the RIG-I-dependent IFN induction. This is the first time that such a function was described for a defective RNA-encoded protein, a finding that has several important implications with regard to deciphering viral protein functions and options for immunostimulatory approaches. Furthermore, this is an example of how influenza viruses may acquire novel polypeptides with altered functions from its limited genome.
Vyšlo v časopise: Evidence for a Novel Mechanism of Influenza Virus-Induced Type I Interferon Expression by a Defective RNA-Encoded Protein. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004924
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004924Souhrn
Error-prone polymerase function of RNA viruses can result in expression of defective RNAs harboring internal deletions of various sizes. Small subgenomic RNAs are strong inducers of the antiviral response by serving as pathogen-associated patterns that are predominantly detected by cellular sensors. Recently, it has been shown that influenza A virus defective RNAs are not only generated upon passages in cell culture, but also in infected humans, indicating that these subgenomic RNAs may also be relevant in infections in vivo. Here, we characterize a novel defective RNA derived from the PB2 segment of a highly pathogenic H5N1 influenza A virus. This RNA encodes a 10 kDa peptide (PB2Δ) which activates type I interferon (IFN) responses through direct interaction with the adapter protein MAVS, a key component of the RIG-I-dependent IFN induction. This is the first time that such a function was described for a defective RNA-encoded protein, a finding that has several important implications with regard to deciphering viral protein functions and options for immunostimulatory approaches. Furthermore, this is an example of how influenza viruses may acquire novel polypeptides with altered functions from its limited genome.
Zdroje
1. Wise HM, Foeglein A, Sun J, Dalton RM, Patel S, Howard W, Anderson EC, Barclay WS, Digard P. A complicated message: Identification of a novel PB1-related protein translated from influenza A virus segment 2 mRNA. J Virol. 2009 Aug;83(16):8021–31. doi: 10.1128/JVI.00826-09 19494001
2. Wise HM, Hutchinson EC, Jagger BW, Stuart AD, Kang ZH, Robb N, Schwartzman LM, Kash JC, Fodor E, Firth AE, Gog JR, Taubenberger JK, Digard P. Identification of a novel splice variant form of the influenza a virus m2 ion channel with an antigenically distinct ectodomain. PLoS Pathog. 2012 Nov;8(11):e1002998. doi: 10.1371/journal.ppat.1002998 23133386
3. Jagger BW, Wise HM, Kash JC, Walters KA, Wills NM, Xiao YL, Dunfee RL, Schwartzman LM, Ozinsky A, Bell GL, Dalton RM, Lo A, Efstathiou S, Atkins JF, Firth AE, Taubenberger JK, Digard P. An overlapping protein-coding region in influenza A virus segment 3 modulates the host response. Science. 2012 Jul 13;337(6091):199–204. doi: 10.1126/science.1222213 22745253
4. Muramoto Y, Noda T, Kawakami E, Akkina R, Kawaoka Y. Identification of novel influenza A virus proteins translated from PA mRNA. J Virol. 2013 Mar;87(5):2455–62. doi: 10.1128/JVI.02656-12 23236060
5. Bouvier NM, Palese P. The biology of influenza viruses. Vaccine. 2008 Sep 12;26 Suppl 4:D49–53. 19230160
6. Hutchinson EC, von Kirchbach JC, Gog JR, Digard P. Genome packaging in influenza A virus. J Gen Virol. 2010 Feb;91(Pt 2):313–28.
7. Davis AR, Hiti AL, Nayak DP. Influenza defective interfering viral RNA is formed by internal deletion of genomic RNA. Proc Natl Acad Sci U S A. 1980 Jan;77(1):215–9. 6928614
8. Nayak DP, Sivasubramanian N, Davis AR, Cortini R, Sung J. Complete sequence analyses show that two defective interfering influenza viral RNAs contain a single internal deletion of a polymerase gene. Proc Natl Acad Sci U S A. 1982 Apr;79(7):2216–20. 6954536
9. Huang AS, Baltimore D. Defective viral particles and viral disease processes. Nature. 1970 Apr 25;226(5243):325–7. 5439728
10. Jennings PA, Finch JT, Winter G, Robertson JS. Does the higher order structure of the influenza virus ribonucleoprotein guide sequence rearrangements in influenza viral RNA? Cell. 1983 Sep;34(2):619–27. 6616623
11. Marriott AC, Dimmock NJ. Defective interfering viruses and their potential as antiviral agents. Rev Med Virol. 2010 Jan;20(1):51–62. doi: 10.1002/rmv.641 20041441
12. Odagiri T, Tashiro M. Segment-specific noncoding sequences of the influenza virus genome RNA are involved in the specific competition between defective interfering RNA and its progenitor RNA segment at the virion assembly step. J Virol. 1997 Mar;71(3):2138–45. 9032347
13. Odagiri T, Tominaga K, Tobita K, Ohta S. An amino acid change in the non-structural NS2 protein of an influenza A virus mutant is responsible for the generation of defective interfering (DI) particles by amplifying DI RNAs and suppressing complementary RNA synthesis. J Gen Virol. 1994 Jan;75 (Pt 1)(Pt 1):43–53.
14. Janda JM, Davis AR, Nayak DP, De BK. Diversity and generation of defective interfering influenza virus particles. Virology. 1979 May;95(1):48–58. 442544
15. Von Magnus P. Propagation of the PR8 strain of influenza A virus in chick embryos. III. properties of the incomplete virus produced in serial passages of undiluted virus. Acta Pathol Microbiol Scand. 1951;29(2):157–81. 14902470
16. Saira K, Lin X, DePasse JV, Halpin R, Twaddle A, Stockwell T, Angus B, Cozzi-Lepri A, Delfino M, Dugan V, Dwyer DE, Freiberg M, Horban A, Losso M, Lynfield R, Wentworth DN, Holmes EC, Davey R, Wentworth DE, Ghedin E, INSIGHT FLU002 Study Group, INSIGHT FLU003 Study Group. Sequence analysis of in vivo defective interfering-like RNA of influenza A H1N1 pandemic virus. J Virol. 2013 Jul;87(14):8064–74. doi: 10.1128/JVI.00240-13 23678180
17. Baum A, Sachidanandam R, Garcia-Sastre A. Preference of RIG-I for short viral RNA molecules in infected cells revealed by next-generation sequencing. Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16303–8. doi: 10.1073/pnas.1005077107 20805493
18. Randall RE, Goodbourn S. Interferons and viruses: An interplay between induction, signalling, antiviral responses and virus countermeasures. J Gen Virol. 2008 Jan;89(Pt 1):1–47. 18089727
19. Tapia K, Kim WK, Sun Y, Mercado-Lopez X, Dunay E, Wise M, Adu M, Lopez CB. Defective viral genomes arising in vivo provide critical danger signals for the triggering of lung antiviral immunity. PLoS Pathog. 2013 Oct;9(10):e1003703. doi: 10.1371/journal.ppat.1003703 24204261
20. Penn CR, Mahy BW. Novel polypeptides encoded by influenza virus subgenomic (DI type) virion RNAs. Virus Res. 1985 Nov;3(4):311–21. 4072398
21. Akkina RK, Chambers TM, Nayak DP. Expression of defective-interfering influenza virus-specific transcripts and polypeptides in infected cells. J Virol. 1984 Aug;51(2):395–403. 6205168
22. Chen W, Calvo PA, Malide D, Gibbs J, Schubert U, Bacik I, Basta S, O'Neill R, Schickli J, Palese P, Henklein P, Bennink JR, Yewdell JW. A novel influenza A virus mitochondrial protein that induces cell death. Nat Med. 2001 Dec;7(12):1306–12. 11726970
23. Tauber S, Ligertwood Y, Quigg-Nicol M, Dutia BM, Elliott RM. Behaviour of influenza A viruses differentially expressing segment 2 gene products in vitro and in vivo. J Gen Virol. 2012 Apr;93(Pt 4):840–9. doi: 10.1099/vir.0.039966-0 22190016
24. Schmolke M, Manicassamy B, Pena L, Sutton T, Hai R, Varga ZT, Hale BG, Steel J, Perez DR, Garcia-Sastre A. Differential contribution of PB1-F2 to the virulence of highly pathogenic H5N1 influenza A virus in mammalian and avian species. PLoS Pathog. 2011 Aug;7(8):e1002186. doi: 10.1371/journal.ppat.1002186 21852950
25. Mazur I, Anhlan D, Mitzner D, Wixler L, Schubert U, Ludwig S. The proapoptotic influenza A virus protein PB1-F2 regulates viral polymerase activity by interaction with the PB1 protein. Cell Microbiol. 2008 May;10(5):1140–52. doi: 10.1111/j.1462-5822.2008.01116.x 18182088
26. Dudek SE, Wixler L, Nordhoff C, Nordmann A, Anhlan D, Wixler V, Ludwig S. The influenza virus PB1-F2 protein has interferon antagonistic activity. Biol Chem. 2011 Dec;392(12):1135–44. doi: 10.1515/BC.2011.174 22050228
27. Varga ZT, Ramos I, Hai R, Schmolke M, Garcia-Sastre A, Fernandez-Sesma A, Palese P. The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein. PLoS Pathog. 2011 Jun;7(6):e1002067. doi: 10.1371/journal.ppat.1002067 21695240
28. Bao Y, Bolotov P, Dernovoy D, Kiryutin B, Zaslavsky L, Tatusova T, Ostell J, Lipman D. The influenza virus resource at the national center for biotechnology information. J Virol. 2008 Jan;82(2):596–601. 17942553
29. Nayak DP, Tobita K, Janda JM, Davis AR, De BK. Homologous interference mediated by defective interfering influenza virus derived from a temperature-sensitive mutant of influenza virus. J Virol. 1978 Oct;28(1):375–86. 702654
30. Hoffmann E, Neumann G, Kawaoka Y, Hobom G, Webster RG. A DNA transfection system for generation of influenza A virus from eight plasmids. Proc Natl Acad Sci U S A. 2000 May 23;97(11):6108–13. 10801978
31. Dimmock NJ, Rainsford EW, Scott PD, Marriott AC. Influenza virus protecting RNA: An effective prophylactic and therapeutic antiviral. J Virol. 2008 Sep;82(17):8570–8. doi: 10.1128/JVI.00743-08 18579602
32. Easton AJ, Scott PD, Edworthy NL, Meng B, Marriott AC, Dimmock NJ. A novel broad-spectrum treatment for respiratory virus infections: Influenza-based defective interfering virus provides protection against pneumovirus infection in vivo. Vaccine. 2011 Mar 24;29(15):2777–84. doi: 10.1016/j.vaccine.2011.01.102 21320545
33. Scott PD, Meng B, Marriott AC, Easton AJ, Dimmock NJ. Defective interfering influenza A virus protects in vivo against disease caused by a heterologous influenza B virus. J Gen Virol. 2011 Sep;92(Pt 9):2122–32. doi: 10.1099/vir.0.034132-0 21632569
34. Pichlmair A, Schulz O, Tan CP, Naslund TI, Liljestrom P, Weber F, Reis e Sousa C. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates. Science. 2006 Nov 10;314(5801):997–1001. 17038589
35. Koerner I, Kochs G, Kalinke U, Weiss S, Staeheli P. Protective role of beta interferon in host defense against influenza A virus. J Virol. 2007 Feb;81(4):2025–30. 17151098
36. Brown EG, Liu H, Kit LC, Baird S, Nesrallah M. Pattern of mutation in the genome of influenza A virus on adaptation to increased virulence in the mouse lung: Identification of functional themes. Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6883–8. 11371620
37. Gabriel G, Dauber B, Wolff T, Planz O, Klenk HD, Stech J. The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host. Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18590–5. 16339318
38. Hatta M, Gao P, Halfmann P, Kawaoka Y. Molecular basis for high virulence of hong kong H5N1 influenza A viruses. Science. 2001 Sep 7;293(5536):1840–2. 11546875
39. Mehle A, Doudna JA. An inhibitory activity in human cells restricts the function of an avian-like influenza virus polymerase. Cell Host Microbe. 2008 Aug 14;4(2):111–22. doi: 10.1016/j.chom.2008.06.007 18692771
40. Graef KM, Vreede FT, Lau YF, McCall AW, Carr SM, Subbarao K, Fodor E. The PB2 subunit of the influenza virus RNA polymerase affects virulence by interacting with the mitochondrial antiviral signaling protein and inhibiting expression of beta interferon. J Virol. 2010 Sep;84(17):8433–45. doi: 10.1128/JVI.00879-10 20538852
41. Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, Shu HB. VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell. 2005 Sep 16;19(6):727–40. 16153868
42. Seth RB, Sun L, Ea CK, Chen ZJ. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell. 2005 Sep 9;122(5):669–82. 16125763
43. Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature. 2005 Oct 20;437(7062):1167–72. 16177806
44. Patel D, Schultz LW, Umland TC. Influenza A polymerase subunit PB2 possesses overlapping binding sites for polymerase subunit PB1 and human MAVS proteins. Virus Res. 2012 Dec 12
45. Carr SM, Carnero E, Garcia-Sastre A, Brownlee GG, Fodor E. Characterization of a mitochondrial-targeting signal in the PB2 protein of influenza viruses. Virology. 2006 Jan 20;344(2):492–508. 16242167
46. Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O, Akira S. IPS-1, an adaptor triggering RIG-I - and Mda5-mediated type I interferon induction. Nat Immunol. 2005 Oct;6(10):981–8. 16127453
47. Kochs G, Garcia-Sastre A, Martinez-Sobrido L. Multiple anti-interferon actions of the influenza A virus NS1 protein. J Virol. 2007 Jul;81(13):7011–21. 17442719
48. Iwai A, Shiozaki T, Kawai T, Akira S, Kawaoka Y, Takada A, Kida H, Miyazaki T. Influenza A virus polymerase inhibits type I interferon induction by binding to interferon beta promoter stimulator 1. J Biol Chem. 2010 Oct 15;285(42):32064–74. doi: 10.1074/jbc.M110.112458 20699220
49. de Jong MD, Simmons CP, Thanh TT, Hien VM, Smith GJ, Chau TN, Hoang DM, Chau NV, Khanh TH, Dong VC, Qui PT, Cam BV, Ha do Q, Guan Y, Peiris JS, Chinh NT, Hien TT, Farrar J. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat Med. 2006 Oct;12(10):1203–7. 16964257
50. Cilloniz C, Shinya K, Peng X, Korth MJ, Proll SC, Aicher LD, Carter VS, Chang JH, Kobasa D, Feldmann F, Strong JE, Feldmann H, Kawaoka Y, Katze MG. Lethal influenza virus infection in macaques is associated with early dysregulation of inflammatory related genes. PLoS Pathog. 2009 Oct;5(10):e1000604. doi: 10.1371/journal.ppat.1000604 19798428
51. Carter MJ, Mahy BW. Incomplete avian influenza virus contains a defective non-interfering component. Arch Virol. 1982;71(1):13–25. 7065901
52. Brooke CB. Biological activities of 'noninfectious' influenza A virus particles. Future Virol. 2014 Jan;9(1):41–51. 25067941
53. Sugiyama K, Obayashi E, Kawaguchi A, Suzuki Y, Tame JR, Nagata K, Park SY. Structural insight into the essential PB1-PB2 subunit contact of the influenza virus RNA polymerase. EMBO J. 2009 Jun 17;28(12):1803–11. doi: 10.1038/emboj.2009.138 19461581
54. Poole E, Elton D, Medcalf L, Digard P. Functional domains of the influenza A virus PB2 protein: Identification of NP - and PB1-binding sites. Virology. 2004 Mar 30;321(1):120–33. 15033571
55. Cheung CY, Poon LL, Lau AS, Luk W, Lau YL, Shortridge KF, Gordon S, Guan Y, Peiris JS. Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: A mechanism for the unusual severity of human disease? Lancet. 2002 Dec 7;360(9348):1831–7. 12480361
56. Teijaro JR, Walsh KB, Cahalan S, Fremgen DM, Roberts E, Scott F, Martinborough E, Peach R, Oldstone MB, Rosen H. Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection. Cell. 2011 Sep 16;146(6):980–91. doi: 10.1016/j.cell.2011.08.015 21925319
57. Börgeling Y, Schmolke M, Viemann D, Nordhoff C, Roth J, Ludwig S. Inhibition of p38 mitogen-activated protein kinase impairs influenza virus-induced primary and secondary host gene responses and protects mice from lethal H5N1 infection. J Biol Chem. 2014 Jan 3;289(1):13–27. doi: 10.1074/jbc.M113.469239 24189062
58. Abt M, de Jonge J, Laue M, Wolff T. Improvement of H5N1 influenza vaccine viruses: Influence of internal gene segments of avian and human origin on production and hemagglutinin content. Vaccine. 2011 Jul 18;29(32):5153–62. doi: 10.1016/j.vaccine.2011.05.036 21624413
59. Zielecki F, Semmler I, Kalthoff D, Voss D, Mauel S, Gruber AD, Beer M, Wolff T. Virulence determinants of avian H5N1 influenza A virus in mammalian and avian hosts: Role of the C-terminal ESEV motif in the viral NS1 protein. J Virol. 2010 Oct;84(20):10708–18. doi: 10.1128/JVI.00610-10 20686040
60. Hoffmann E, Stech J, Guan Y, Webster RG, Perez DR. Universal primer set for the full-length amplification of all influenza A viruses. Arch Virol. 2001 Dec;146(12):2275–89. 11811679
61. Seyer R, Hrincius ER, Ritzel D, Abt M, Mellmann A, Marjuki H, Kuhn J, Wolff T, Ludwig S, Ehrhardt C. Synergistic adaptive mutations in the hemagglutinin and polymerase acidic protein lead to increased virulence of pandemic 2009 H1N1 influenza A virus in mice. J Infect Dis. 2012 Jan 15;205(2):262–71. doi: 10.1093/infdis/jir716 22102733
62. Borchert N, Dieterich C, Krug K, Schutz W, Jung S, Nordheim A, Sommer RJ, Macek B. Proteogenomics of pristionchus pacificus reveals distinct proteome structure of nematode models. Genome Res. 2010 Jun;20(6):837–46. doi: 10.1101/gr.103119.109 20237107
63. Rappsilber J, Mann M, Ishihama Y. Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTips. Nat Protoc. 2007;2(8):1896–906. 17703201
64. Carpy A, Krug K, Graf S, Koch A, Popic S, Hauf S, Macek B. Absolute proteome and phosphoproteome dynamics during the cell cycle of schizosaccharomyces pombe (fission yeast). Mol Cell Proteomics. 2014 Aug;13(8):1925–36. doi: 10.1074/mcp.M113.035824 24763107
65. Cox J, Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol. 2008 Dec;26(12):1367–72. doi: 10.1038/nbt.1511 19029910
66. Cox J, Neuhauser N, Michalski A, Scheltema RA, Olsen JV, Mann M. Andromeda: A peptide search engine integrated into the MaxQuant environment. J Proteome Res. 2011 Apr 1;10(4):1794–805. doi: 10.1021/pr101065j 21254760
67. Elias JE, Gygi SP. Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry. Nat Methods. 2007 Mar;4(3):207–14. 17327847
68. Luig C, Kother K, Dudek SE, Gaestel M, Hiscott J, Wixler V, Ludwig S. MAP kinase-activated protein kinases 2 and 3 are required for influenza A virus propagation and act via inhibition of PKR. FASEB J. 2010 Oct;24(10):4068–77. doi: 10.1096/fj.10-158766 20484669
69. Ehrhardt C, Schmolke M, Matzke A, Knoblauch A, Will C, Wixler V, Ludwig S. Polyethylenimine, a cost-effective transfection reagent. Signal Transduction. 2006;6(3):179–84.
70. Ehrhardt C, Kardinal C, Wurzer WJ, Wolff T, von Eichel-Streiber C, Pleschka S, Planz O, Ludwig S. Rac1 and PAK1 are upstream of IKK-epsilon and TBK-1 in the viral activation of interferon regulatory factor-3. FEBS Lett. 2004 Jun 4;567(2–3):230–8. 15178349
71. Kawakami E, Watanabe T, Fujii K, Goto H, Watanabe S, Noda T, Kawaoka Y. Strand-specific real-time RT-PCR for distinguishing influenza vRNA, cRNA, and mRNA. J Virol Methods. 2011 Apr;173(1):1–6. doi: 10.1016/j.jviromet.2010.12.014 21185869
72. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 2001 Dec;25(4):402–8. 11846609
73. Mo D, Raabe CA, Reinhardt R, Brosius J, Rozhdestvensky TS. Alternative processing as evolutionary mechanism for the origin of novel nonprotein coding RNAs. Genome Biol Evol. 2013;5(11):2061–71. doi: 10.1093/gbe/evt155 24132753
Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium
Článek Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary TuberculosisČlánek Circumventing . Virulence by Early Recruitment of Neutrophils to the Lungs during Pneumonic PlagueČlánek Admixture in Humans of Two Divergent Populations Associated with Different Macaque Host SpeciesČlánek Human and Murine Clonal CD8+ T Cell Expansions Arise during Tuberculosis Because of TCR SelectionČlánek Selective Recruitment of Nuclear Factors to Productively Replicating Herpes Simplex Virus GenomesČlánek Fob1 and Fob2 Proteins Are Virulence Determinants of via Facilitating Iron Uptake from FerrioxamineČlánek Remembering MumpsČlánek Human Cytomegalovirus miR-UL112-3p Targets TLR2 and Modulates the TLR2/IRAK1/NFκB Signaling PathwayČlánek Induces the Premature Death of Human Neutrophils through the Action of Its Lipopolysaccharide
Článok vyšiel v časopisePLOS Pathogens
Najčítanejšie tento týždeň
2015 Číslo 5- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
-
Všetky články tohto čísla
- Parasites and Their Heterophagic Appetite for Disease
- The Elusive Role of the Prion Protein and the Mechanism of Toxicity in Prion Disease
- Intestinal Colonization Dynamics of
- Activation of Typhi-Specific Regulatory T Cells in Typhoid Disease in a Wild-Type . Typhi Challenge Model
- The Engineering of a Novel Ligand in gH Confers to HSV an Expanded Tropism Independent of gD Activation by Its Receptors
- Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary Tuberculosis
- Group Selection and Contribution of Minority Variants during Virus Adaptation Determines Virus Fitness and Phenotype
- Phosphatidic Acid Produced by Phospholipase D Promotes RNA Replication of a Plant RNA Virus
- A Ribonucleoprotein Complex Protects the Interleukin-6 mRNA from Degradation by Distinct Herpesviral Endonucleases
- Characterization of Transcriptional Responses to Different Aphid Species Reveals Genes that Contribute to Host Susceptibility and Non-host Resistance
- Circumventing . Virulence by Early Recruitment of Neutrophils to the Lungs during Pneumonic Plague
- Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus
- Manipulation of the Xanthophyll Cycle Increases Plant Susceptibility to
- Ly6C Monocytes Regulate Parasite-Induced Liver Inflammation by Inducing the Differentiation of Pathogenic Ly6C Monocytes into Macrophages
- Admixture in Humans of Two Divergent Populations Associated with Different Macaque Host Species
- Expression in the Fat Body Is Required in the Defense Against Parasitic Wasps in
- Experimental Evolution of an RNA Virus in Wild Birds: Evidence for Host-Dependent Impacts on Population Structure and Competitive Fitness
- Inhibition and Reversal of Microbial Attachment by an Antibody with Parasteric Activity against the FimH Adhesin of Uropathogenic .
- The EBNA-2 N-Terminal Transactivation Domain Folds into a Dimeric Structure Required for Target Gene Activation
- Human and Murine Clonal CD8+ T Cell Expansions Arise during Tuberculosis Because of TCR Selection
- The NLRP3 Inflammasome Is a Pathogen Sensor for Invasive via Activation of α5β1 Integrin at the Macrophage-Amebae Intercellular Junction
- Sequential Conformational Changes in the Morbillivirus Attachment Protein Initiate the Membrane Fusion Process
- A Two-Component DNA-Prime/Protein-Boost Vaccination Strategy for Eliciting Long-Term, Protective T Cell Immunity against
- cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission
- Response Regulator VxrB Controls Colonization and Regulates the Type VI Secretion System
- Evidence for a Novel Mechanism of Influenza Virus-Induced Type I Interferon Expression by a Defective RNA-Encoded Protein
- Dust Devil: The Life and Times of the Fungus That Causes Valley Fever
- TNF-α Induced by Hepatitis C Virus via TLR7 and TLR8 in Hepatocytes Supports Interferon Signaling via an Autocrine Mechanism
- The Recent Evolution of a Maternally-Inherited Endosymbiont of Ticks Led to the Emergence of the Q Fever Pathogen,
- L-Rhamnosylation of Wall Teichoic Acids Promotes Resistance to Antimicrobial Peptides by Delaying Interaction with the Membrane
- Rapid Sequestration of by Neutrophils Contributes to the Development of Chronic Lesion
- Selective Recruitment of Nuclear Factors to Productively Replicating Herpes Simplex Virus Genomes
- The Expression of Functional Vpx during Pathogenic SIVmac Infections of Rhesus Macaques Suppresses SAMHD1 in CD4 Memory T Cells
- Fob1 and Fob2 Proteins Are Virulence Determinants of via Facilitating Iron Uptake from Ferrioxamine
- TRAF1 Coordinates Polyubiquitin Signaling to Enhance Epstein-Barr Virus LMP1-Mediated Growth and Survival Pathway Activation
- Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site
- Remembering Mumps
- The Role of Horizontal Gene Transfer in the Evolution of the Oomycetes
- Advances and Challenges in Computational Prediction of Effectors from Plant Pathogenic Fungi
- Investigating Fungal Outbreaks in the 21st Century
- Systems Biology for Biologists
- How Does the Dinoflagellate Parasite Outsmart the Immune System of Its Crustacean Hosts?
- FCRL5 Delineates Functionally Impaired Memory B Cells Associated with Exposure
- Phospholipase D1 Couples CD4 T Cell Activation to c-Myc-Dependent Deoxyribonucleotide Pool Expansion and HIV-1 Replication
- Influenza A Virus on Oceanic Islands: Host and Viral Diversity in Seabirds in the Western Indian Ocean
- Geometric Constraints Dominate the Antigenic Evolution of Influenza H3N2 Hemagglutinin
- Widespread Recombination, Reassortment, and Transmission of Unbalanced Compound Viral Genotypes in Natural Arenavirus Infections
- Gammaherpesvirus Co-infection with Malaria Suppresses Anti-parasitic Humoral Immunity
- A Single Protein S-acyl Transferase Acts through Diverse Substrates to Determine Cryptococcal Morphology, Stress Tolerance, and Pathogenic Outcome
- Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance
- Mechanisms of Stage-Transcending Protection Following Immunization of Mice with Late Liver Stage-Arresting Genetically Attenuated Malaria Parasites
- The Myelin and Lymphocyte Protein MAL Is Required for Binding and Activity of ε-Toxin
- Genome-Wide Identification of the Target Genes of AP2-O, a AP2-Family Transcription Factor
- An Atypical Mitochondrial Carrier That Mediates Drug Action in
- Human Cytomegalovirus miR-UL112-3p Targets TLR2 and Modulates the TLR2/IRAK1/NFκB Signaling Pathway
- Helminth Infection and Commensal Microbiota Drive Early IL-10 Production in the Skin by CD4 T Cells That Are Functionally Suppressive
- Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection
- ExoT Induces Atypical Anoikis Apoptosis in Target Host Cells by Transforming Crk Adaptor Protein into a Cytotoxin
- Discovery of a Small Non-AUG-Initiated ORF in Poleroviruses and Luteoviruses That Is Required for Long-Distance Movement
- Induces the Premature Death of Human Neutrophils through the Action of Its Lipopolysaccharide
- Varicella Viruses Inhibit Interferon-Stimulated JAK-STAT Signaling through Multiple Mechanisms
- Paradoxical Immune Responses in Non-HIV Cryptococcal Meningitis
- Recovery of Recombinant Crimean Congo Hemorrhagic Fever Virus Reveals a Function for Non-structural Glycoproteins Cleavage by Furin
- PLOS Pathogens
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- Human Cytomegalovirus miR-UL112-3p Targets TLR2 and Modulates the TLR2/IRAK1/NFκB Signaling Pathway
- Paradoxical Immune Responses in Non-HIV Cryptococcal Meningitis
- Expression in the Fat Body Is Required in the Defense Against Parasitic Wasps in
- Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance
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