-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
Recombination in Enteroviruses Is a Biphasic Replicative Process Involving the Generation of Greater-than Genome Length ‘Imprecise’ Intermediates
The rapid evolution of most positive-sense RNA viruses enables them to escape immune surveillance and adapt to new hosts. Genetic variation arises due to their error-prone RNA polymerases and by recombination of viral genomes in co-infected cells. We have developed a novel approach to analyse the poorly understood mechanism of recombination using a poliovirus model system. We characterised the initial viable recombinants and demonstrate the majority are longer than genome length due to an imprecise crossover event that duplicates part of the genome. These viruses are unfit, but rapidly lose the duplicated material and regain full fitness upon serial passage, a process we term resolution. We show this is a replicative recombination process by modifying the fidelity of the viral polymerase, or replication complex coalescence, using methods that have no influence on a previously reported, less efficient, non-replicative recombination mechanism. We conclude that recombination is a biphasic process involving separate generation and resolution events. These new insights into an important evolutionary mechanism have implications for our understanding of virus evolution through partial genome duplication, they suggest ways in which recombination might be modified and provides an approach that may be exploited to analyse recombination in other RNA viruses.
Vyšlo v časopise: Recombination in Enteroviruses Is a Biphasic Replicative Process Involving the Generation of Greater-than Genome Length ‘Imprecise’ Intermediates. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004191
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004191Souhrn
The rapid evolution of most positive-sense RNA viruses enables them to escape immune surveillance and adapt to new hosts. Genetic variation arises due to their error-prone RNA polymerases and by recombination of viral genomes in co-infected cells. We have developed a novel approach to analyse the poorly understood mechanism of recombination using a poliovirus model system. We characterised the initial viable recombinants and demonstrate the majority are longer than genome length due to an imprecise crossover event that duplicates part of the genome. These viruses are unfit, but rapidly lose the duplicated material and regain full fitness upon serial passage, a process we term resolution. We show this is a replicative recombination process by modifying the fidelity of the viral polymerase, or replication complex coalescence, using methods that have no influence on a previously reported, less efficient, non-replicative recombination mechanism. We conclude that recombination is a biphasic process involving separate generation and resolution events. These new insights into an important evolutionary mechanism have implications for our understanding of virus evolution through partial genome duplication, they suggest ways in which recombination might be modified and provides an approach that may be exploited to analyse recombination in other RNA viruses.
Zdroje
1. DomingoE, HollandJJ (1997) RNA virus mutations and fitness for survival. Annu Rev Microbiol 51 : 151–178.
2. EigenM (1996) On the nature of virus quasispecies. Trends Microbiol 4 : 216–218.
3. GristNR, BellEJ, AssaadF (1978) Enteroviruses in human disease. Prog Med Virol 24 : 114–157.
4. Knowles NJ, Hovi T, Hyypia T, King AMQ, Lindberg AM, et al. (2012) Picornaviridae. In: King AMQ, Adams MJ, Carstens EB, Lefkowitz EJ, editors. Virus Taxonomy: Classification and Nomenclature of Viruses: Ninth Report of the International Committee on Taxonomy of Viruses. San Diego: Elsevier. pp. 855–880.
5. CaroV, GuillotS, DelpeyrouxF, CrainicR (2001) Molecular strategy for ‘serotyping’ of human enteroviruses. J Gen Virol 82 : 79–91.
6. ObersteMS, MaherK, KilpatrickDR, PallanschMA (1999) Molecular evolution of the human enteroviruses: correlation of serotype with VP1 sequence and application to picornavirus classification. J Virol 73 : 1941–1948.
7. ObersteMS, MaherK, KilpatrickDR, FlemisterMR, BrownBA, et al. (1999) Typing of human enteroviruses by partial sequencing of VP1. J Clin Microbiol 37 : 1288–1293.
8. PalaciosG, CasasI, TenorioA, FreireC (2002) Molecular identification of enterovirus by analyzing a partial VP1 genomic region with different methods. J Clin Microbiol 40 : 182–192.
9. BrownBA, ObersteMS, AlexanderJP, KennettML, PallanschMA (1999) Molecular epidemiology and evolution of enterovirus 71 strains isolated from 1970 to 1998. J Virol 73 : 9969–9975.
10. ChuaBH, McMinnPC, LamSK, ChuaKB (2001) Comparison of the complete nucleotide sequences of echovirus 7 strain UMMC and the prototype (Wallace) strain demonstrates significant genetic drift over time. J Gen Virol 82 : 2629–2639.
11. KünkelU, SchreierE (2000) Genetic variability within the VP1 coding region of echovirus type 30 isolates. Arch Virol 145 : 1455–1464.
12. MartínJ, DunnG, HullR, PatelV, MinorPD (2000) Evolution of the Sabin strain of type 3 poliovirus in an immunodeficient patient during the entire 637-day period of virus excretion. J Virol 74 : 3001–3010.
13. SimmondsP, WelchJ (2006) Frequency and dynamics of recombination within different species of human enteroviruses. J Virol 80 : 483–493.
14. TakedaN, TanimuraM, MiyamuraK (1994) Molecular evolution of the major capsid protein VP1 of enterovirus 70. J Virol 68 : 854–862.
15. AnderssonP, EdmanK, LindbergAM (2002) Molecular analysis of the echovirus 18 prototype: evidence of interserotypic recombination with echovirus 9. Virus Res 85 : 71–83.
16. LindbergAM, AnderssonP, SavolainenC, MuldersMN, HoviT (2003) Evolution of the genome of Human enterovirus B: incongruence between phylogenies of the VP1 and 3CD regions indicates frequent recombination within the species. J Gen Virol 84 : 1223–1235.
17. ChevaliezS, SzendröiA, CaroV, BalanantJ, GuillotS, et al. (2004) Molecular comparison of echovirus 11 strains circulating in Europe during an epidemic of multisystem hemorrhagic disease of infants indicates that evolution generally occurs by recombination. Virology 325 : 56–70.
18. GuillotS, CaroV, CuervoN, KorotkovaE, CombiescuM, et al. (2000) Natural genetic exchanges between vaccine and wild poliovirus strains in humans. J Virol 74 : 8434–8443.
19. CuervoNS, GuillotS, RomanenkovaN, CombiescuM, Aubert-CombiescuA, et al. (2001) Genomic features of intertypic recombinant sabin poliovirus strains excreted by primary vaccinees. J Virol 75 : 5740–5751.
20. LukashevAN, LashkevichVA, KorolevaGA, IlonenJ, HinkkanenAE (2004) Recombination in uveitis-causing enterovirus strains. J Gen Virol 85 : 463–470.
21. LukashevAN, LashkevichVA, IvanovaOE, KorolevaGA, HinkkanenAE, et al. (2005) Recombination in circulating Human enterovirus B: independent evolution of structural and non-structural genome regions. J Gen Virol 86 : 3281–3290.
22. LukashevAN, IvanovaOE, EremeevaTP, GmylLV (2008) Analysis of echovirus 30 isolates from Russia and new independent states revealing frequent recombination and reemergence of ancient lineages. J Clin Microbiol 46 : 665–670.
23. McWilliam LeitchE, BendigJ, CabrerizoM, CardosaJ, HyypiäT, et al. (2009) Transmission networks and population turnover of echovirus 30. J Virol 83 : 2109–2118.
24. McWilliam LeitchEC, CabrerizoM, CardosaJ, HarvalaH, IvanovaOE, et al. (2010) Evolutionary dynamics and temporal/geographical correlates of recombination in the human enterovirus echovirus types 9, 11, and 30. J Virol 84 : 9292–9300.
25. McWilliam LeitchEC, CabrerizoM, CardosaJ, HarvalaH, IvanovaOE, et al. (2012) The association of recombination events in the founding and emergence of subgenogroup evolutionary lineages of human enterovirus 71. J Virol 86 : 2676–2685.
26. NorderH, BjerregaardL, MagniusLO (2002) Open reading frame sequence of an Asian enterovirus 73 strain reveals that the prototype from California is recombinant. J Gen Virol 83 : 1721–1728.
27. KewO, Morris-GlasgowV, LandaverdeM, BurnsC, ShawJ, et al. (2002) Outbreak of poliomyelitis in Hispaniola associated with circulating type 1 vaccine-derived poliovirus. Science 296 : 356–359.
28. ObersteMS, MaherK, PallanschMA (2004) Evidence for frequent recombination within species human enterovirus B based on complete genomic sequences of all thirty-seven serotypes. J Virol 78 : 855–867.
29. ObersteMS, PeñarandaS, PallanschMA (2004) RNA recombination plays a major role in genomic change during circulation of coxsackie B viruses. J Virol 78 : 2948–2955.
30. OprisanG, CombiescuM, GuillotS, CaroV, CombiescuA, et al. (2002) Natural genetic recombination between co-circulating heterotypic enteroviruses. J Gen Virol 83 : 2193–2200.
31. SanttiJ, HyypiäT, KinnunenL, SalminenM (1999) Evidence of recombination among enteroviruses. J Virol 73 : 8741–8749.
32. SanttiJ, VainionpääR, HyypiäT (1999) Molecular detection and typing of human picornaviruses. Virus Res 62 : 177–183.
33. SanttiJ, HarvalaH, KinnunenL, HyypiäT (2000) Molecular epidemiology and evolution of coxsackievirus A9. J Gen Virol 81 : 1361–1372.
34. McIntyreCL, McWilliam LeitchEC, Savolainen-KopraC, HoviT, SimmondsP (2010) Analysis of genetic diversity and sites of recombination in human rhinovirus species. C. J Virol 84 : 10297–10310.
35. KimH, KimK, KimDW, JungHD, Min CheongH, et al. (2013) Identification of Recombinant Human Rhinovirus A and C in Circulating Strains from Upper and Lower Respiratory Infections. PLoS One 8: e68081.
36. MartínJ, SamoilovichE, DunnG, LackenbyA, FeldmanE, et al. (2002) Isolation of an intertypic poliovirus capsid recombinant from a child with vaccine-associated paralytic poliomyelitis. J Virol 76 : 10921–10928.
37. SmuraT, BlomqvistS, PaananenA, VuorinenT, SobotováZ, et al. (2007) Enterovirus surveillance reveals proposed new serotypes and provides new insight into enterovirus 5′-untranslated region evolution. J Gen Virol 88 : 2520–2526.
38. YozwiakNL, Skewes-CoxP, GordonA, SaborioS, KuanG, et al. (2010) Human enterovirus 109: a novel interspecies recombinant enterovirus isolated from a case of acute pediatric respiratory illness in Nicaragua. J Virol 84 : 9047–9058.
39. TapparelC, JunierT, GerlachD, CordeyS, Van BelleS, et al. (2007) New complete genome sequences of human rhinoviruses shed light on their phylogeny and genomic features. BMC Genomics 8 : 224.
40. BolanakiE, KottaridiC, MarkoulatosP, KyriakopoulouZ, MargaritisL, et al. (2007) Partial 3D gene sequences of Coxsackie viruses reveal interspecies exchanges. Virus Genes 35 : 129–140.
41. RohllJ, PercyN, LeyR, EvansD, AlmondJ, et al. (1994) The 5′-untranslated regions of picornavirus RNAs contain independent functional domains essential for RNA replication and translation. J Virol 68 : 4384–4391.
42. GromeierM, AlexanderL, WimmerE (1996) Internal ribosomal entry site substitution eliminates neurovirulence in intergeneric poliovirus recombinants. Proc Natl Acad Sci U S A 93 : 2370–2375.
43. EggerD, BienzK (2002) Recombination of poliovirus RNA proceeds in mixed replication complexes originating from distinct replication start sites. J Virol 76 : 10960–10971.
44. WorobeyM, HolmesEC (1999) Evolutionary aspects of recombination in RNA viruses. J Gen Virol 80 (Pt 10): 2535–2543.
45. JiangP, FaaseJA, ToyodaH, PaulA, WimmerE, et al. (2007) Evidence for emergence of diverse polioviruses from C-cluster coxsackie A viruses and implications for global poliovirus eradication. Proc Natl Acad Sci U S A 104 : 9457–9462.
46. LiuY, WangC, MuellerS, PaulAV, WimmerE, et al. (2010) Direct interaction between two viral proteins, the nonstructural protein 2C and the capsid protein VP3, is required for enterovirus morphogenesis. PLoS Pathog 6: e1001066.
47. KirkegaardK, BaltimoreD (1986) The mechanism of RNA recombination in poliovirus. Cell 47 : 433–443.
48. ArnoldJJ, CameronCE (1999) Poliovirus RNA-dependent RNA polymerase (3Dpol) is sufficient for template switching in vitro. J Biol Chem 274 : 2706–2716.
49. NagyPD, SimonAE (1997) New insights into the mechanisms of RNA recombination. Virology 235 : 1–9.
50. GmylAP, BelousovEV, MaslovaSV, KhitrinaEV, ChetverinAB, et al. (1999) Nonreplicative RNA recombination in poliovirus. J Virol 73 : 8958–8965.
51. GmylAP, KorshenkoSA, BelousovEV, KhitrinaEV, AgolVI (2003) Nonreplicative homologous RNA recombination: promiscuous joining of RNA pieces? RNA 9 : 1221–1231.
52. GalleiA, PankrazA, ThielHJ, BecherP (2004) RNA recombination in vivo in the absence of viral replication. J Virol 78 : 6271–6281.
53. ScheelTK, GalliA, LiYP, MikkelsenLS, GottweinJM, et al. (2013) Productive homologous and non-homologous recombination of hepatitis C virus in cell culture. PLoS Pathog 9: e1003228.
54. EminiEA, LeibowitzJ, DiamondDC, BoninJ, WimmerE (1984) Recombinants of Mahoney and Sabin strain poliovirus type 1: analysis of in vitro phenotypic markers and evidence that resistance to guanidine maps in the nonstructural proteins. Virology 137 : 74–85.
55. GoodfellowIG, PolacekC, AndinoR, EvansDJ (2003) The poliovirus 2C cis-acting replication element-mediated uridylylation of VPg is not required for synthesis of negative-sense genomes. Journal of General Virology 84 : 2359–2363.
56. GoodfellowI, ChaudhryY, RichardsonA, MeredithJ, AlmondJ, et al. (2000) Identification of a cis-acting replication element within the poliovirus coding region. J Virol 74 : 4590–4600.
57. GoodfellowI, KerriganD, EvansD (2003) Structure and function analysis of the poliovirus cis-acting replication element (CRE). RNA 9 : 124–137.
58. BartonDJ, FlaneganJB (1997) Synchronous replication of poliovirus RNA: initiation of negative-strand RNA synthesis requires the guanidine-inhibited activity of protein 2C. J Virol 71 : 8482–8489.
59. CrottyS, MaagD, ArnoldJJ, ZhongW, LauJY, et al. (2000) The broad-spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen. Nat Med 6 : 1375–1379.
60. PfeifferJK, KirkegaardK (2003) A single mutation in poliovirus RNA-dependent RNA polymerase confers resistance to mutagenic nucleotide analogs via increased fidelity. Proc Natl Acad Sci U S A 100 : 7289–7294.
61. PfeifferJK, KirkegaardK (2005) Increased fidelity reduces poliovirus fitness and virulence under selective pressure in mice. PLoS Pathog 1: e11.
62. EggerD, BienzK (2005) Intracellular location and translocation of silent and active poliovirus replication complexes. J Gen Virol 86 : 707–718.
63. DoedensJ, MaynellLA, KlymkowskyMW, KirkegaardK (1994) Secretory pathway function, but not cytoskeletal integrity, is required in poliovirus infection. Arch Virol Suppl 9 : 159–172.
64. RunckelC, WestessonO, AndinoR, DeRisiJL (2013) Identification and manipulation of the molecular determinants influencing poliovirus recombination. PLoS Pathog 9: e1003164.
65. KingAM (1988) Preferred sites of recombination in poliovirus RNA: an analysis of 40 intertypic cross-over sequences. Nucleic Acids Res 16 : 11705–11723.
66. DedepsidisE, KyriakopoulouZ, PliakaV, MarkoulatosP (2010) Correlation between recombination junctions and RNA secondary structure elements in poliovirus Sabin strains. Virus Genes 41 : 181–191.
67. SimmondsP, TuplinA, EvansD (2004) Detection of genome-scale ordered RNA structure (GORS) in genomes of positive-stranded RNA viruses: Implications for virus evolution and host persistence. RNA 10 : 1337–1351.
68. DavisM, SaganSM, PezackiJP, EvansDJ, SimmondsP (2008) Bioinformatic and Physical Characterizations of Genome-Scale Ordered RNA Structure in Mammalian RNA Viruses. Journal of Virology 82 : 11824–11836.
69. Simon-LoriereE, HolmesEC (2011) Why do RNA viruses recombine? Nat Rev Microbiol 9 : 617–626.
70. HahnCS, LustigS, StraussEG, StraussJH (1988) Western equine encephalitis virus is a recombinant virus. Proc Natl Acad Sci U S A 85 : 5997–6001.
71. CammackN, PhillipsA, DunnG, PatelV, MinorPD (1988) Intertypic genomic rearrangements of poliovirus strains in vaccinees. Virology 167 : 507–514.
72. YangCF, NaguibT, YangSJ, NasrE, JorbaJ, et al. (2003) Circulation of endemic type 2 vaccine-derived poliovirus in Egypt from 1983 to 1993. J Virol 77 : 8366–8377.
73. AduF, IberJ, BukbukD, GumedeN, YangSJ, et al. (2007) Isolation of recombinant type 2 vaccine-derived poliovirus (VDPV) from a Nigerian child. Virus Res 127 : 17–25.
74. HeathL, van der WaltE, VarsaniA, MartinDP (2006) Recombination patterns in aphthoviruses mirror those found in other picornaviruses. J Virol 80 : 11827–11832.
75. De GraziaS, MediciMC, PintoP, MoschidouP, TummoloF, et al. (2012) Genetic heterogeneity and recombination in human type 2 astroviruses. J Clin Microbiol 50 : 3760–3764.
76. TwiddySS, HolmesEC (2003) The extent of homologous recombination in members of the genus Flavivirus. J Gen Virol 84 : 429–440.
77. MooreJ, JironkinA, ChandlerD, BurroughsN, EvansDJ, et al. (2011) Recombinants between Deformed wing virus and Varroa destructor virus-1 may prevail in Varroa destructor-infested honeybee colonies. Journal of General Virology 92 : 156–161.
78. PilipenkoEV, GmylAP, AgolVI (1995) A model for rearrangements in RNA genomes. Nucleic Acids Res 23 : 1870–1875.
79. RomanovaLI, BlinovVM, TolskayaEA, ViktorovaEG, KolesnikovaMS, et al. (1986) The primary structure of crossover regions of intertypic poliovirus recombinants: a model of recombination between RNA genomes. Virology 155 : 202–213.
80. TolskayaEA, RomanovaLI, BlinovVM, ViktorovaEG, SinyakovAN, et al. (1987) Studies on the recombination between RNA genomes of poliovirus: the primary structure and nonrandom distribution of crossover regions in the genomes of intertypic poliovirus recombinants. Virology 161 : 54–61.
81. BarclayW, LiQ, HutchinsonG, MoonD, RichardsonA, et al. (1998) Encapsidation studies of poliovirus subgenomic replicons. J Gen Virol 79 (Pt 7): 1725–1734.
82. PercyN, BarclayWS, SullivanM, AlmondJW (1992) A poliovirus replicon containing the chloramphenicol acetyltransferase gene can be used to study the replication and encapsidation of poliovirus RNA. J Virol 66 : 5040–5046.
83. MorascoBJ, SharmaN, ParillaJ, FlaneganJB (2003) Poliovirus cre(2C)-dependent synthesis of VPgpUpU is required for positive - but not negative-strand RNA synthesis. J Virol 77 : 5136–5144.
84. MurrayKE, BartonDJ (2003) Poliovirus CRE-dependent VPg uridylylation is required for positive-strand RNA synthesis but not for negative-strand RNA synthesis. J Virol 77 : 4739–4750.
85. JarvisTC, KirkegaardK (1992) Poliovirus RNA recombination: mechanistic studies in the absence of selection. EMBO J 11 : 3135–3145.
86. DuggalR, WimmerE (1999) Genetic recombination of poliovirus in vitro and in vivo: temperature-dependent alteration of crossover sites. Virology 258 : 30–41.
87. MollaA, JangSK, PaulAV, ReuerQ, WimmerE (1992) Cardioviral Internal Ribosomal Entry Site Is Functional in a Genetically Engineered Dicistronic Poliovirus. Nature 356 : 255–257.
88. CuconatiA, XiangW, LahserF, PfisterT, WimmerE (1998) A protein linkage map of the P2 nonstructural proteins of poliovirus. J Virol 72 : 1297–1307.
89. BarcoA, CarrascoL (1998) Identification of regions of poliovirus 2BC protein that are involved in cytotoxicity. J Virol 72 : 3560–3570.
90. SuhyDA, GiddingsTH, KirkegaardK (2000) Remodeling the endoplasmic reticulum by poliovirus infection and by individual viral proteins: an autophagy-like origin for virus-induced vesicles. J Virol 74 : 8953–8965.
91. TeterinaNL, LevensonE, RinaudoMS, EggerD, BienzK, et al. (2006) Evidence for functional protein interactions required for poliovirus RNA replication. J Virol 80 : 5327–5337.
92. AtkinsonNJ, WitteveldtJ, EvansDJ, SimmondsP (2014) The influence of CpG and UpA dinucleotide frequencies on RNA virus replication and characterization of the innate cellular pathways underlying virus attenuation and enhanced replication. Nucleic Acids Res 42(7): 4527–4545.
93. YunZ, LaraC, JohanssonB, Lorenzana de RiveraI, SönnerborgA (1996) Discrepancy of hepatitis C virus genotypes as determined by phylogenetic analysis of partial NS5 and core sequences. J Med Virol 49 : 155–160.
94. González-CandelasF, López-LabradorFX, BrachoMA (2011) Recombination in hepatitis C virus. Viruses 3 : 2006–2024.
95. FreistadtMS, VaccaroJA, EberleKE (2007) Biochemical characterization of the fidelity of poliovirus RNA-dependent RNA polymerase. Virol J 4 : 44.
96. RajuR, SubramaniamSV, HajjouM (1995) Genesis of Sindbis virus by in vivo recombination of nonreplicative RNA precursors. J Virol 69 : 7391–7401.
97. JacksonAL, O'NeillH, MareeF, BlignautB, CarrilloC, et al. (2007) Mosaic structure of foot-and-mouth disease virus genomes. J Gen Virol 88 : 487–492.
98. HogleJM, ChowM, FilmanDJ (1985) Three-dimensional structure of poliovirus at 2.9 A resolution. Science 229 : 1358–1365.
99. ForssS, SchallerH (1982) A tandem repeat gene in a picornavirus. Nucleic Acids Res 10 : 6441–6450.
100. Palmenberg A, Neubauer D, Skern T (2010) Genome organisation and encoded proteins. In: Ehrenfeld E, Domingo E, Roos R, editors. The Picornaviruses. Washington DC: ASM Press.
101. Simon-LoriereE, HolmesEC (2013) Gene duplication is infrequent in the recent evolutionary history of RNA viruses. Mol Biol Evol 30 : 1263–1269.
102. NakashimaN, ShibuyaN (2006) Multiple coding sequences for the genome-linked virus protein (VPg) in dicistroviruses. J Invertebr Pathol 92 : 100–104.
103. PengCW, PeremyslovVV, MushegianAR, DawsonWO, DoljaVV (2001) Functional specialization and evolution of leader proteinases in the family Closteroviridae. J Virol 75 : 12153–12160.
104. GorbalenyaAE, PringleFM, ZeddamJL, LukeBT, CameronCE, et al. (2002) The palm subdomain-based active site is internally permuted in viral RNA-dependent RNA polymerases of an ancient lineage. J Mol Biol 324 : 47–62.
105. Minor PD (1985) Growth, Assay and Purification of Picornaviruses. In: Mahy BWJ, editor. Virology: A practical approach. Oxford: IRL Press. pp. 25–41.
106. AndinoR, RieckhofGE, AchacosoPL, BaltimoreD (1993) Poliovirus RNA Synthesis Utilizes an RNP Complex Formed Around the 5′-End of Viral RNA. EMBO Journal 12 : 3587–3598.
107. LarkinMA, BlackshieldsG, BrownNP, ChennaR, McGettiganPA, et al. (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23 : 2947–2948.
108. SimmondsP (2012) SSE: a nucleotide and amino acid sequence analysis platform. BMC Res Notes 5 : 50.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium
Článek Recruitment of RED-SMU1 Complex by Influenza A Virus RNA Polymerase to Control Viral mRNA SplicingČlánek Systematic Phenotyping of a Large-Scale Deletion Collection Reveals Novel Antifungal Tolerance GenesČlánek The Contribution of Social Behaviour to the Transmission of Influenza A in a Human Population
Článok vyšiel v časopisePLOS Pathogens
Najčítanejšie tento týždeň
2014 Číslo 6- 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
- Fungal Nail Infections (Onychomycosis): A Never-Ending Story?
- BdlA, DipA and Induced Dispersion Contribute to Acute Virulence and Chronic Persistence of
- Morphotype Transition and Sexual Reproduction Are Genetically Associated in a Ubiquitous Environmental Pathogen
- A Nucleic-Acid Hydrolyzing Single Chain Antibody Confers Resistance to DNA Virus Infection in HeLa Cells and C57BL/6 Mice
- HopW1 from Disrupts the Actin Cytoskeleton to Promote Virulence in Arabidopsis
- Ly6C Monocytes Become Alternatively Activated Macrophages in Schistosome Granulomas with Help from CD4+ Cells
- Recruitment of RED-SMU1 Complex by Influenza A Virus RNA Polymerase to Control Viral mRNA Splicing
- Contribution of Specific Residues of the β-Solenoid Fold to HET-s Prion Function, Amyloid Structure and Stability
- Antibody Responses to : Role in Pathogenesis and Diagnosis of Encephalitis?
- Discovery of a Novel Compound with Anti-Venezuelan Equine Encephalitis Virus Activity That Targets the Nonstructural Protein 2
- Activation of Focal Adhesion Kinase by Suppresses Autophagy via an Akt/mTOR Signaling Pathway and Promotes Bacterial Survival in Macrophages
- Crossing the Interspecies Barrier: Opening the Door to Zoonotic Pathogens
- Catching Fire: , Macrophages, and Pyroptosis
- IscR Is Essential for Type III Secretion and Virulence
- Selective Chemical Inhibition of Quorum Sensing in Promotes Host Defense with Minimal Impact on Resistance
- The Glycosylated Rv1860 Protein of Inhibits Dendritic Cell Mediated TH1 and TH17 Polarization of T Cells and Abrogates Protective Immunity Conferred by BCG
- A Genome-Wide Tethering Screen Reveals Novel Potential Post-Transcriptional Regulators in
- Structural Insights into SraP-Mediated Adhesion to Host Cells
- Human IGF1 Regulates Midgut Oxidative Stress and Epithelial Homeostasis to Balance Lifespan and resistance in
- Cycling Empirical Antibiotic Therapy in Hospitals: Meta-Analysis and Models
- Rab11 Regulates Trafficking of -sialidase to the Plasma Membrane through the Contractile Vacuole Complex of
- Mitogen and Stress Activated Kinases Act Co-operatively with CREB during the Induction of Human Cytomegalovirus Immediate-Early Gene Expression from Latency
- Profilin Promotes Recruitment of Ly6C CCR2 Inflammatory Monocytes That Can Confer Resistance to Bacterial Infection
- A Central Role for Carbon-Overflow Pathways in the Modulation of Bacterial Cell Death
- An Invertebrate Warburg Effect: A Shrimp Virus Achieves Successful Replication by Altering the Host Metabolome via the PI3K-Akt-mTOR Pathway
- The Highly Conserved Bacterial RNase YbeY Is Essential in , Playing a Critical Role in Virulence, Stress Regulation, and RNA Processing
- A Virulent Strain of Deformed Wing Virus (DWV) of Honeybees () Prevails after -Mediated, or , Transmission
- Systematic Phenotyping of a Large-Scale Deletion Collection Reveals Novel Antifungal Tolerance Genes
- Ubiquitin-Mediated Response to Microsporidia and Virus Infection in
- Preclinical Detection of Variant CJD and BSE Prions in Blood
- Toll-Like Receptor 8 Agonist and Bacteria Trigger Potent Activation of Innate Immune Cells in Human Liver
- Progressive Proximal-to-Distal Reduction in Expression of the Tight Junction Complex in Colonic Epithelium of Virally-Suppressed HIV+ Individuals
- The Triggering Receptor Expressed on Myeloid Cells 2 Inhibits Complement Component 1q Effector Mechanisms and Exerts Detrimental Effects during Pneumococcal Pneumonia
- Differential Activation of Acid Sphingomyelinase and Ceramide Release Determines Invasiveness of into Brain Endothelial Cells
- Forward Genetic Screening Identifies a Small Molecule That Blocks Growth by Inhibiting Both Host- and Parasite-Encoded Kinases
- Defining Immune Engagement Thresholds for Control of Virus-Driven Lymphoproliferation
- Growth Factor and Th2 Cytokine Signaling Pathways Converge at STAT6 to Promote Arginase Expression in Progressive Experimental Visceral Leishmaniasis
- Multimeric Assembly of Host-Pathogen Adhesion Complexes Involved in Apicomplexan Invasion
- Biogenesis of Influenza A Virus Hemagglutinin Cross-Protective Stem Epitopes
- Adequate Th2-Type Response Associates with Restricted Bacterial Growth in Latent Mycobacterial Infection of Zebrafish
- Protective Efficacy of Passive Immunization with Monoclonal Antibodies in Animal Models of H5N1 Highly Pathogenic Avian Influenza Virus Infection
- Fructose-Asparagine Is a Primary Nutrient during Growth of in the Inflamed Intestine
- The Calcium-Dependent Protein Kinase 3 of Influences Basal Calcium Levels and Functions beyond Egress as Revealed by Quantitative Phosphoproteome Analysis
- A Translocated Effector Required for Dissemination from Derma to Blood Safeguards Migratory Host Cells from Damage by Co-translocated Effectors
- Functional Characterization of a Novel Family of Acetylcholine-Gated Chloride Channels in
- Both α2,3- and α2,6-Linked Sialic Acids on O-Linked Glycoproteins Act as Functional Receptors for Porcine Sapovirus
- The Contribution of Social Behaviour to the Transmission of Influenza A in a Human Population
- MicroRNA-146a Provides Feedback Regulation of Lyme Arthritis but Not Carditis during Infection with
- Recombination in Enteroviruses Is a Biphasic Replicative Process Involving the Generation of Greater-than Genome Length ‘Imprecise’ Intermediates
- Cytoplasmic Viral RNA-Dependent RNA Polymerase Disrupts the Intracellular Splicing Machinery by Entering the Nucleus and Interfering with Prp8
- and Are Associated with Murine Susceptibility to Infection and Human Sepsis
- PLOS Pathogens
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- Profilin Promotes Recruitment of Ly6C CCR2 Inflammatory Monocytes That Can Confer Resistance to Bacterial Infection
- Fungal Nail Infections (Onychomycosis): A Never-Ending Story?
- Contribution of Specific Residues of the β-Solenoid Fold to HET-s Prion Function, Amyloid Structure and Stability
- The Highly Conserved Bacterial RNase YbeY Is Essential in , Playing a Critical Role in Virulence, Stress Regulation, and RNA Processing
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