1887

Abstract

Low-passage clinical isolates of chikungunya virus (CHIKV) were found to be a mixture of large- and small-plaque viruses, with small-plaque viruses being the predominant species. To investigate the contribution of plaque variants to the pathology of the joint, primary human fibroblast-like synoviocytes (HFLS) were used. Large- and small-plaque viruses were purified from two clinical isolates, CHIKV-031C and CHIKV-033C, and were designated CHIKV-031L and CHIKV-031S and CHIKV-033L and CHIKV-033S, respectively. The replication efficiencies of these viruses in HFLSs were compared and it was found that CHIKV-031S and CHIKV-033S replicated with the highest efficiency, while the parental clinical isolates had the lowest efficiency. Interestingly, the cytopathic effects (CPE) induced by these viruses correlated with neither the efficiency of replication nor the plaque size. The small-plaque viruses and the clinical isolates induced cell death rapidly, while large-plaque viruses induced slow CPE in which only 50 % of the cells in infected cultures were rounded up and detached on day 5 of infection. The production of proinflammatory cytokines and chemokines from infected HFLSs was evaluated. The results showed that the large-plaque viruses and the clinical isolates, but not small-plaque variants, were potent inducers of IL-6, IL-8 and MCP-1, and were able to migrate monocytes/macrophages efficiently. Sequencing data revealed a number of differences in amino acid sequences between the small- and large-plaque viruses. The results suggest that it is common for clinical isolates of CHIKV to be heterogeneous, while the variants may have distinct roles in the pathology of the joint.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001039
2018-03-08
2019-10-16
Loading full text...

Full text loading...

/deliver/fulltext/jgv/99/4/525.html?itemId=/content/journal/jgv/10.1099/jgv.0.001039&mimeType=html&fmt=ahah

References

  1. Cavrini F, Gaibani P, Pierro AM, Rossini G, Landini MP et al. Chikungunya: an emerging and spreading arthropod-borne viral disease. J Infect Dev Ctries 2009; 3: 744– 752 [PubMed]
    [Google Scholar]
  2. Burt FJ, Rolph MS, Rulli NE, Mahalingam S, Heise MT. Chikungunya: a re-emerging virus. Lancet 2012; 379: 662– 671 [CrossRef] [PubMed]
    [Google Scholar]
  3. Burt FJ, Chen W, Miner JJ, Lenschow DJ, Merits A et al. Chikungunya virus: an update on the biology and pathogenesis of this emerging pathogen. Lancet Infect Dis 2017; 17: e107-17 [CrossRef] [PubMed]
    [Google Scholar]
  4. Solignat M, Gay B, Higgs S, Briant L, Devaux C. Replication cycle of chikungunya: a re-emerging arbovirus. Virology 2009; 393: 183– 197 [CrossRef] [PubMed]
    [Google Scholar]
  5. Powers AM, Brault AC, Tesh RB, Weaver SC. Re-emergence of Chikungunya and O'nyong-nyong viruses: evidence for distinct geographical lineages and distant evolutionary relationships. J Gen Virol 2000; 81: 471– 479 [CrossRef] [PubMed]
    [Google Scholar]
  6. Robinson MC. An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952-53. I. Clinical features. Trans R Soc Trop Med Hyg 1955; 49: 28– 32 [PubMed] [Crossref]
    [Google Scholar]
  7. Halstead SB, Scanlon JE, Umpaivit P, Udomsakdi S. Dengue and Chikungunya virus infection in man in Thailand, 1962–1964. IV. Epidemiologic studies in the Bangkok metropolitan area. Am J Trop Med Hyg 1969; 18: 997– 1021 [PubMed] [Crossref]
    [Google Scholar]
  8. Fischer M, Staples JE. Notes from the field: Chikungunya virus spreads in the Americas - Caribbean and South America, 2013-2014. MMWR Morb Mortal Wkly Rep 2014; 63: 500– 501 [PubMed]
    [Google Scholar]
  9. Cauchemez S, Ledrans M, Poletto C, Quenel P, de Valk H et al. Local and regional spread of Chikungunya fever in the Americas. Euro Surveill 2014; 19: 20854 [CrossRef] [PubMed]
    [Google Scholar]
  10. Kautz TF, Díaz-González EE, Erasmus JH, Malo-García IR, Langsjoen RM et al. Chikungunya virus as cause of febrile illness outbreak, Chiapas, Mexico, 2014. Emerg Infect Dis 2015; 21: 2070– 2073 [CrossRef] [PubMed]
    [Google Scholar]
  11. Singh SK, Unni SK. Chikungunya virus: host pathogen interaction. Rev Med Virol 2011; 21: 78– 88 [CrossRef] [PubMed]
    [Google Scholar]
  12. Chow A, Her Z, Ong EK, Chen JM, Dimatatac F et al. Persistent arthralgia induced by Chikungunya virus infection is associated with interleukin-6 and granulocyte macrophage colony-stimulating factor. J Infect Dis 2011; 203: 149– 157 [CrossRef] [PubMed]
    [Google Scholar]
  13. Dupuis-Maguiraga L, Noret M, Brun S, Le Grand R, Gras G et al. Chikungunya disease: infection-associated markers from the acute to the chronic phase of arbovirus-induced arthralgia. PLoS Negl Trop Dis 2012; 6: e1446 [CrossRef] [PubMed]
    [Google Scholar]
  14. Pialoux G, Gaüzère BA, Jauréguiberry S, Strobel M. Chikungunya, an epidemic arbovirosis. Lancet Infect Dis 2007; 7: 319– 327 [CrossRef] [PubMed]
    [Google Scholar]
  15. Simon F, Parola P, Grandadam M, Fourcade S, Oliver M et al. Chikungunya infection: an emerging rheumatism among travelers returned from Indian Ocean islands. Report of 47 cases. Medicine 2007; 86: 123– 137 [CrossRef] [PubMed]
    [Google Scholar]
  16. Miner JJ, Aw-Yeang HX, Fox JM, Taffner S, Malkova ON et al. Brief Report: Chikungunya viral arthritis in the United States: a mimic of seronegative rheumatoid arthritis. Arthritis Rheumatol 2015; 67: 1214– 1220 [CrossRef] [PubMed]
    [Google Scholar]
  17. Feldstein LR, Rowhani-Rahbar A, Staples JE, Weaver MR, Halloran ME et al. Persistent arthralgia associated with Chikungunya virus outbreak, US Virgin Islands, December 2014–February 2016. Emerg Infect Dis 2017; 23: 673– 676 [CrossRef] [PubMed]
    [Google Scholar]
  18. Thiberville SD, Boisson V, Gaudart J, Simon F, Flahault A et al. Chikungunya fever: a clinical and virological investigation of outpatients on Reunion Island, South-West Indian Ocean. PLoS Negl Trop Dis 2013; 7: e2004 [CrossRef] [PubMed]
    [Google Scholar]
  19. Hoarau JJ, Jaffar Bandjee MC, Krejbich Trotot P, das T, Li-Pat-Yuen G et al. Persistent chronic inflammation and infection by Chikungunya arthritogenic alphavirus in spite of a robust host immune response. J Immunol 2010; 184: 5914– 5927 [CrossRef] [PubMed]
    [Google Scholar]
  20. Gardner J, Anraku I, Le TT, Larcher T, Major L et al. Chikungunya virus arthritis in adult wild-type mice. J Virol 2010; 84: 8021– 8032 [CrossRef] [PubMed]
    [Google Scholar]
  21. Morrison TE, Oko L, Montgomery SA, Whitmore AC, Lotstein AR et al. A mouse model of Chikungunya virus-induced musculoskeletal inflammatory disease: evidence of arthritis, tenosynovitis, myositis, and persistence. Am J Pathol 2011; 178: 32– 40 [CrossRef] [PubMed]
    [Google Scholar]
  22. Wilson JA, Prow NA, Schroder WA, Ellis JJ, Cumming HE et al. RNA-Seq analysis of Chikungunya virus infection and identification of granzyme A as a major promoter of arthritic inflammation. PLoS Pathog 2017; 13: e1006155 [CrossRef] [PubMed]
    [Google Scholar]
  23. Sourisseau M, Schilte C, Casartelli N, Trouillet C, Guivel-Benhassine F et al. Characterization of reemerging Chikungunya virus. PLoS Pathog 2007; 3: e89 [CrossRef] [PubMed]
    [Google Scholar]
  24. Lohachanakul J, Phuklia W, Thannagith M, Thonsakulprasert T, Ubol S. High concentrations of circulating interleukin-6 and monocyte chemotactic protein-1 with low concentrations of interleukin-8 were associated with severe Chikungunya fever during the 2009– 2010 outbreak in Thailand. Microbiol Immunol 2012; 56: 134– 138 [CrossRef] [PubMed]
    [Google Scholar]
  25. Phuklia W, Kasisith J, Modhiran N, Rodpai E, Thannagith M et al. Osteoclastogenesis induced by CHIKV-infected fibroblast-like synoviocytes: a possible interplay between synoviocytes and monocytes/macrophages in CHIKV-induced arthralgia/arthritis. Virus Res 2013; 177: 179– 188 [CrossRef] [PubMed]
    [Google Scholar]
  26. Sawicki DL, Perri S, Polo JM, Sawicki SG. Role for nsP2 proteins in the cessation of alphavirus minus-strand synthesis by host cells. J Virol 2006; 80: 360– 371 [CrossRef] [PubMed]
    [Google Scholar]
  27. Wasonga C, Inoue S, Rumberia C, Michuki G, Kimotho J et al. Genetic divergence of Chikungunya virus plaque variants from the Comoros Island (2005). Virus Genes 2015; 51: 323– 328 [CrossRef] [PubMed]
    [Google Scholar]
  28. Lim CK, Nishibori T, Watanabe K, Ito M, Kotaki A et al. Chikungunya virus isolated from a returnee to Japan from Sri Lanka: isolation of two sub-strains with different characteristics. Am J Trop Med Hyg 2009; 81: 865– 868 [CrossRef] [PubMed]
    [Google Scholar]
  29. Chanas AC, Johnson BK, Simpson DI. Characterization of two Chikungunya virus variants. Acta Virol 1979; 23: 128– 136 [PubMed]
    [Google Scholar]
  30. Sugita K, Maru M, Sato K. Biological properties of plaque-size variants of Sendai virus. Microbiol Immunol 1981; 25: 353– 360 [CrossRef] [PubMed]
    [Google Scholar]
  31. Oleszak EL, Leibowitz JL, Rodriguez M. Isolation and characterization of two plaque size variants of Theiler's murine encephalomyelitis virus (DA strain). J Gen Virol 1988; 69: 2413– 2418 [CrossRef] [PubMed]
    [Google Scholar]
  32. Byrnes AP, Griffin DE. Large-plaque mutants of Sindbis virus show reduced binding to heparan sulfate, heightened viremia, and slower clearance from the circulation. J Virol 2000; 74: 644– 651 [CrossRef] [PubMed]
    [Google Scholar]
  33. Wu SC, Lian WC, Hsu LC, Liau MY. Japanese encephalitis virus antigenic variants with characteristic differences in neutralization resistance and mouse virulence. Virus Res 1997; 51: 173– 181 [PubMed] [Crossref]
    [Google Scholar]
  34. Lidbury BA, Rulli NE, Musso CM, Cossetto SB, Zaid A et al. Identification and characterization of a ross river virus variant that grows persistently in macrophages, shows altered disease kinetics in a mouse model, and exhibits resistance to type I interferon. J Virol 2011; 85: 5651– 5663 [CrossRef] [PubMed]
    [Google Scholar]
  35. Reading PC, Pickett DL, Tate MD, Whitney PG, Job ER et al. Loss of a single N-linked glycan from the hemagglutinin of influenza virus is associated with resistance to collectins and increased virulence in mice. Respir Res 2009; 10: 117 [CrossRef] [PubMed]
    [Google Scholar]
  36. Li G, Rice CM. The signal for translational readthrough of a UGA codon in Sindbis virus RNA involves a single cytidine residue immediately downstream of the termination codon. J Virol 1993; 67: 5062– 5067 [PubMed]
    [Google Scholar]
  37. Strauss EG, Rice CM, Strauss JH. Sequence coding for the alphavirus nonstructural proteins is interrupted by an opal termination codon. Proc Natl Acad Sci USA 1983; 80: 5271– 5275 [CrossRef] [PubMed]
    [Google Scholar]
  38. Myles KM, Kelly CL, Ledermann JP, Powers AM. Effects of an opal termination codon preceding the nsP4 gene sequence in the O'Nyong-Nyong virus genome on Anopheles gambiae infectivity. J Virol 2006; 80: 4992– 4997 [CrossRef] [PubMed]
    [Google Scholar]
  39. Tuittila MT, Santagati MG, Röyttä M, Määttä JA, Hinkkanen AE. Replicase complex genes of Semliki Forest virus confer lethal neurovirulence. J Virol 2000; 74: 4579– 4589 [CrossRef] [PubMed]
    [Google Scholar]
  40. Scian R, Barrionuevo P, Giambartolomei GH, de Simone EA, Vanzulli SI et al. Potential role of fibroblast-like synoviocytes in joint damage induced by Brucella abortus infection through production and induction of matrix metalloproteinases. Infect Immun 2011; 79: 3619– 3632 [CrossRef] [PubMed]
    [Google Scholar]
  41. Ng LF, Chow A, Sun YJ, Kwek DJ, Lim PL et al. IL-1beta, IL-6, and RANTES as biomarkers of Chikungunya severity. PLoS One 2009; 4: e4261 [CrossRef] [PubMed]
    [Google Scholar]
  42. Chaaitanya IK, Muruganandam N, Sundaram SG, Kawalekar O, Sugunan AP et al. Role of proinflammatory cytokines and chemokines in chronic arthropathy in CHIKV infection. Viral Immunol 2011; 24: 265– 271 [CrossRef] [PubMed]
    [Google Scholar]
  43. Noret M, Herrero L, Rulli N, Rolph M, Smith PN et al. Interleukin 6, RANKL, and osteoprotegerin expression by Chikungunya virus-infected human osteoblasts. J Infect Dis 2012; 206: 455– 457 [CrossRef] [PubMed]
    [Google Scholar]
  44. Chen W, Foo SS, Rulli NE, Taylor A, Sheng KC et al. Arthritogenic alphaviral infection perturbs osteoblast function and triggers pathologic bone loss. Proc Natl Acad Sci USA 2014; 111: 6040– 6045 [CrossRef] [PubMed]
    [Google Scholar]
  45. Liu XH, Kirschenbaum A, Yao S, Levine AC. Cross-talk between the interleukin-6 and prostaglandin E2 signaling systems results in enhancement of osteoclastogenesis through effects on the osteoprotegerin/receptor activator of nuclear factor-κB (RANK) ligand/RANK system. Endocrinology 2005; 146: 1991– 1998 [CrossRef] [PubMed]
    [Google Scholar]
  46. Mori T, Miyamoto T, Yoshida H, Asakawa M, Kawasumi M et al. IL-1β and TNFα-initiated IL-6-STAT3 pathway is critical in mediating inflammatory cytokines and RANKL expression in inflammatory arthritis. Int Immunol 2011; 23: 701– 712 [CrossRef] [PubMed]
    [Google Scholar]
  47. Georganas C, Liu H, Perlman H, Hoffmann A, Thimmapaya B et al. Regulation of IL-6 and IL-8 expression in rheumatoid arthritis synovial fibroblasts: the dominant role for NF-κB but not C/EBP beta or c-Jun. J Immunol 2000; 165: 7199– 7206 [CrossRef] [PubMed]
    [Google Scholar]
  48. Hwang SY, Kim JY, Kim KW, Park MK, Moon Y et al. IL-17 induces production of IL-6 and IL-8 in rheumatoid arthritis synovial fibroblasts via NF-κB- and PI3-kinase/Akt-dependent pathways. Arthritis Res Ther 2004; 6: R120– 128 [CrossRef] [PubMed]
    [Google Scholar]
  49. Bendre MS, Montague DC, Peery T, Akel NS, Gaddy D et al. Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease. Bone 2003; 33: 28– 37 [CrossRef] [PubMed]
    [Google Scholar]
  50. Wigerblad G, Bas DB, Fernades-Cerqueira C, Krishnamurthy A, Nandakumar KS et al. Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism. Ann Rheum Dis 2016; 75: 730– 738 [CrossRef] [PubMed]
    [Google Scholar]
  51. Chou RC, Kim ND, Sadik CD, Seung E, Lan Y et al. Lipid-cytokine-chemokine cascade drives neutrophil recruitment in a murine model of inflammatory arthritis. Immunity 2010; 33: 266– 278 [CrossRef] [PubMed]
    [Google Scholar]
  52. Lidbury BA, Rulli NE, Suhrbier A, Smith PN, McColl SR et al. Macrophage-derived proinflammatory factors contribute to the development of arthritis and myositis after infection with an arthrogenic alphavirus. J Infect Dis 2008; 197: 1585– 1593 [CrossRef] [PubMed]
    [Google Scholar]
  53. Rulli NE, Rolph MS, Srikiatkhachorn A, Anantapreecha S, Guglielmotti A et al. Protection from arthritis and myositis in a mouse model of acute Chikungunya virus disease by bindarit, an inhibitor of monocyte chemotactic protein-1 synthesis. J Infect Dis 2011; 204: 1026– 1030 [CrossRef] [PubMed]
    [Google Scholar]
  54. Beaucourt S, Bordería AV, Coffey LL, Gnädig NF, Sanz-Ramos M et al. Isolation of fidelity variants of RNA viruses and characterization of virus mutation frequency. J Vis Exp 2011; [CrossRef] [PubMed]
    [Google Scholar]
  55. Lohachanakul J, Phuklia W, Thannagith M, Thongsakulprasert T, Smith DR et al. Differences in response of primary human myoblasts to infection with recent epidemic strains of Chikungunya virus isolated from patients with and without myalgia. J Med Virol 2015; 87: 733– 739 [CrossRef] [PubMed]
    [Google Scholar]
  56. Woods JM, Klosowska K, Spoden DJ, Stumbo NG, Paige DJ et al. A cell-cycle independent role for p21 in regulating synovial fibroblast migration in rheumatoid arthritis. Arthritis Res Ther 2006; 8: R113 [CrossRef] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001039
Loading
/content/journal/jgv/10.1099/jgv.0.001039
Loading

Data & Media loading...

Supplements

Supplementary File 1

PDF

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error