Inter- and Intra-Host Viral Diversity in a Large Seasonal DENV2 Outbreak

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PLOS ONE, v.8, n.8, article ID e70318, 10p, 2013
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Background: High genetic diversity at both inter-and intra-host level are hallmarks of RNA viruses due to the error-prone nature of their genome replication. Several groups have evaluated the extent of viral variability using different RNA virus deep sequencing methods. Although much of this effort has been dedicated to pathogens that cause chronic infections in humans, few studies investigated arthropod-borne, acute viral infections. Methods and Principal Findings: We deep sequenced the complete genome of ten DENV2 isolates from representative classical and severe cases sampled in a large outbreak in Brazil using two different approaches. Analysis of the consensus genomes confirmed the larger extent of the 2010 epidemic in comparison to a previous epidemic caused by the same viruses in another city two years before (genetic distance = 0.002 and 0.0008 respectively). Analysis of viral populations within the host revealed a high level of conservation. After excluding homopolymer regions of 454/Roche generated sequences, we found 10 to 44 variable sites per genome population at a frequency of >1%, resulting in very low intra-host genetic diversity. While up to 60% of all variable sites at intra-host level were non-synonymous changes, only 10% of inter-host variability resulted from non-synonymous mutations, indicative of purifying selection at the population level. Conclusions and Significance: Despite the error-prone nature of RNA-dependent RNA-polymerase, dengue viruses maintain low levels of intra-host variability.
  1. Aaskov J, 2006, SCIENCE, V311, P236, DOI 10.1126/science.1115030
  2. Becker EA, 2012, GENOME BIOL EVOL, V4, P457, DOI 10.1093/gbe/evs029
  3. Bimber BN, 2010, J VIROL, V84, P12087, DOI 10.1128/JVI.01378-10
  4. Brackney DE, 2010, PLOS NEGLECT TROP D, V4, DOI 10.1371/journal.pntd.0000856
  5. Coffey LL, 2008, P NATL ACAD SCI USA, V105, P6970, DOI 10.1073/pnas.0712130105
  7. Descloux E, 2009, PLOS NEGLECT TROP D, V3, DOI 10.1371/journal.pntd.0000493
  8. de Souza VAUF, 2004, J CLIN MICROBIOL, V42, P1782, DOI 10.1128/JCM.42.4.1782-1784.2004
  9. dos Santos Cecilia Luiza Simoes, 2003, Revista do Instituto de Medicina Tropical de Sao Paulo, V45, P11, DOI 10.1590/S0036-46652003000100003
  10. Duffy S, 2008, NAT REV GENET, V9, P267, DOI 10.1038/nrg2323
  11. Edgar RC, 2004, BMC BIOINFORMATICS, V5, P1, DOI 10.1186/1471-2105-5-113
  12. Farci P, 2000, SCIENCE, V288, P339, DOI 10.1126/science.288.5464.339
  13. Farci P, 2000, SEMIN LIVER DIS, V20, P103
  14. Gilles A, 2011, BMC GENOMICS, V12, DOI 10.1186/1471-2164-12-245
  15. Grenfell BT, 2004, SCIENCE, V303, P327, DOI 10.1126/science.1090727
  16. Guilarde AO, 2008, J INFECT DIS, V197, P817, DOI 10.1086/528805
  17. Henn MR, 2012, PLOS PATHOG, V8, DOI 10.1371/journal.ppat.1002529
  18. Holmes EC, 2003, J VIROL, V77, P11296, DOI 10.1128/JVI.77.20.11296-11298.2003
  19. Hoper D, 2012, J VIROL, V86, P1394, DOI 10.1128/JVI.00797-11
  20. Kanesa-thasan N, 1998, EMERG INFECT DIS, V4, P299
  21. Kumar SRP, 2010, J GEN VIROL, V91, P707, DOI 10.1099/vir.0.017954-0
  22. Lai YL, 2007, J CLIN MICROBIOL, V45, P935, DOI 10.1128/JCM.01258-06
  23. Lauck M, 2012, J VIROL, V86, P3952, DOI 10.1128/JVI.06627-11
  24. Li DS, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0019447
  25. MADDISON WP, 1989, FOLIA PRIMATOL, V53, P190, DOI 10.1159/000156416
  26. Murcia PR, 2010, J VIROL, V84, P6943, DOI 10.1128/JVI.00112-10
  27. Ninomiya M, 2012, J CLIN MICROBIOL, V50, P857, DOI 10.1128/JCM.05715-11
  28. Oliveira MF, 2010, EMERG INFECT DIS, V16, P576, DOI 10.3201/eid1603.090996
  30. Parameswaran P, 2012, J VIROL
  31. Pond SLK, 2005, BIOINFORMATICS, V21, P2531, DOI 10.1093/bioinformatics/bti320
  32. Posada D, 2008, MOL BIOL EVOL, V25, P1253, DOI 10.1093/molbev/msn083
  33. Rogozin IB, 2003, MUTAT RES-REV MUTAT, V544, P65, DOI 10.1016/S1383-5742(03)00032-2
  34. Romano CM, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0011811
  35. Ronquist F, 2003, BIOINFORMATICS, V19, P1572, DOI 10.1093/bioinformatics/btg180
  36. Rozera G, 2009, RETROVIROLOGY, V6, DOI 10.1186/1742-4690-6-15
  37. SABINO E, 1993, AIDS RES HUM RETROV, V9, P1265, DOI 10.1089/aid.1993.9.1265
  38. Strauss BS, 1999, MUTAT RES-REV MUTAT, V437, P195, DOI 10.1016/S1383-5742(99)00066-6
  39. Suzuki S, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0019534
  40. Tamura K, 2011, MOL BIOL EVOL, V28, P2731, DOI 10.1093/molbev/msr121
  41. Temporao JG, 2011, EMERG INFECT DIS, V17, P938, DOI 10.3201/eid1705.101681
  42. Thai KTD, 2012, J VIROL, V86, P835, DOI 10.1128/JVI.05985-11
  43. VARTANIAN JP, 1992, AIDS, V6, P1095, DOI 10.1097/00002030-199210000-00005
  44. Vasilakis N, 2009, PLOS PATHOG, V5, DOI 10.1371/journal.ppat.1000467
  45. Wang WK, 2002, VIROLOGY, V303, P181, DOI 10.1006/viro.2002.1635
  46. Wang WK, 2002, J VIROL, V76, P4662, DOI 10.1128/JVI.76.9.4662-4665.2002
  47. Weaver SC, 1999, J VIROL, V73, P4316
  48. [WHO Organization WH], 2009, DENG GUID DIAGN TREA, P147