Chikungunya Virus Neutralization Antigens and Direct Cell-to-Cell Transmission Are Revealed by Human Antibody-Escape Mutants

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Chikungunya virus (CHIKV) is an alphavirus responsible for numerous epidemics throughout Africa and Asia, causing infectious arthritis and reportedly linked with fatal infections in newborns and elderly. Previous studies in animal models indicate that humoral immunity can protect against CHIKV infection, but despite the potential efficacy of B-cell-driven intervention strategies, there are no virus-specific vaccines or therapies currently available. In addition, CHIKV has been reported to elicit long-lasting virus-specific IgM in humans, and to establish long-term persistence in non-human primates, suggesting that the virus might evade immune defenses to establish chronic infections in man. However, the mechanisms of immune evasion potentially employed by CHIKV remain uncharacterized. We previously described two human monoclonal antibodies that potently neutralize CHIKV infection. In the current report, we have characterized CHIKV mutants that escape antibody-dependent neutralization to identify the CHIKV E2 domain B and fusion loop “groove” as the primary determinants of CHIKV interaction with these antibodies. Furthermore, for the first time, we have also demonstrated direct CHIKV cell-to-cell transmission, as a mechanism that involves the E2 domain A and that is associated with viral resistance to antibody-dependent neutralization. Identification of CHIKV sub-domains that are associated with human protective immunity, will pave the way for the development of CHIKV-specific sub-domain vaccination strategies. Moreover, the clear demonstration of CHIKV cell-to-cell transmission and its possible role in the establishment of CHIKV persistence, will also inform the development of future anti-viral interventions. These data shed new light on CHIKV-host interactions that will help to combat human CHIKV infection and inform future studies of CHIKV pathogenesis.

Vyšlo v časopise: Chikungunya Virus Neutralization Antigens and Direct Cell-to-Cell Transmission Are Revealed by Human Antibody-Escape Mutants. PLoS Pathog 7(12): e32767. doi:10.1371/journal.ppat.1002390
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002390

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1. RobinsonMC 1955 An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952-53. I. Clinical features. Trans R Soc Trop Med Hyg 49 28 32

2. CharrelRNde LamballerieXRaoultD 2007 Chikungunya outbreaks–the globalization of vectorborne diseases. N Engl J Med 356 769 771

3. HerZKamYWLinRTNgLF 2009 Chikungunya: a bending reality. Microbes Infect 11 1165 1176

4. EnserinkM 2007 Infectious diseases. Chikungunya: no longer a third world disease. Science 318 1860 1861

5. RezzaGNicolettiLAngeliniRRomiRFinarelliAC 2007 Infection with chikungunya virus in Italy: an outbreak in a temperate region. Lancet 370 1840 1846

6. GrandadamMCaroVPlumetSThibergeJMSouaresY 2011 Chikungunya virus, southeastern france. Emerg Infect Dis 17 910 913

7. StaplesJEBreimanRFPowersAM 2009 Chikungunya fever: an epidemiological review of a re-emerging infectious disease. Clin Infect Dis 49 942 948

8. BorgheriniGPoubeauPJossaumeAGouixACotteL 2008 Persistent arthralgia associated with chikungunya virus: a study of 88 adult patients on reunion island. Clin Infect Dis 47 469 475

9. SoumahoroMKGerardinPBoellePYPerrauJFianuA 2009 Impact of Chikungunya virus infection on health status and quality of life: a retrospective cohort study. PLoS One 4 e7800

10. BouquillardECombeB 2009 A report of 21 cases of rheumatoid arthritis following Chikungunya fever. A mean follow-up of two years. Joint Bone Spine 76 654 657

11. GerardinPBarauGMichaultABintnerMRandrianaivoH 2008 Multidisciplinary prospective study of mother-to-child chikungunya virus infections on the island of La Reunion. PLoS Med 5 e60

12. MichaultAStaikowskyF 2009 Chikungunya: first steps toward specific treatment and prophylaxis. J Infect Dis 200 489 491

13. StraussJHStraussEG 1994 The alphaviruses: gene expression, replication, and evolution. Microbiol Rev 58 491 562

14. KhanAHMoritaKParquet MdMCHasebeFMathengeEG 2002 Complete nucleotide sequence of chikungunya virus and evidence for an internal polyadenylation site. J Gen Virol 83 3075 3084

15. SimizuBYamamotoKHashimotoKOgataT 1984 Structural proteins of Chikungunya virus. J Virol 51 254 258

16. KielianMHeleniusA 1985 pH-induced alterations in the fusogenic spike protein of Semliki Forest virus. J Cell Biol 101 2284 2291

17. WhiteJHeleniusA 1980 pH-dependent fusion between the Semliki Forest virus membrane and liposomes. Proc Natl Acad Sci U S A 77 3273 3277

18. DubuissonJRiceCM 1993 Sindbis virus attachment: isolation and characterization of mutants with impaired binding to vertebrate cells. J Virol 67 3363 3374

19. StraussEGStecDSSchmaljohnALStraussJH 1991 Identification of antigenically important domains in the glycoproteins of Sindbis virus by analysis of antibody escape variants. J Virol 65 4654 4664

20. GibbonsDLVaneyMCRousselAVigourouxAReillyB 2004 Conformational change and protein-protein interactions of the fusion protein of Semliki Forest virus. Nature 427 320 325

21. LescarJRousselAWienMWNavazaJFullerSD 2001 The Fusion glycoprotein shell of Semliki Forest virus: an icosahedral assembly primed for fusogenic activation at endosomal pH. Cell 105 137 148

22. VossJEVaneyMCDuquerroySVonrheinCGirard-BlancC 2010 Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography. Nature 468 709 712

23. LiLJoseJXiangYKuhnRJRossmannMG 2010 Structural changes of envelope proteins during alphavirus fusion. Nature 468 705 708

24. CoudercTKhandoudiNGrandadamMVisseCGangneuxN 2009 Prophylaxis and therapy for Chikungunya virus infection. J Infect Dis 200 516 523

25. ChopraAAnuradhaVLagoo-JoshiVKunjirVSalviS 2008 Chikungunya virus aches and pains: an emerging challenge. Arthritis Rheum 58 2921 2922

26. HoarauJJJaffar BandjeeMCKrejbich TrototPDasTLi-Pat-YuenG 2010 Persistent chronic inflammation and infection by Chikungunya arthritogenic alphavirus in spite of a robust host immune response. J Immunol 184 5914 5927

27. LabadieKLarcherTJoubertCManniouiADelacheB 2010 Chikungunya disease in nonhuman primates involves long-term viral persistence in macrophages. J Clin Invest 120 894 906

28. WarterLLeeCYThiagarajanRGrandadamMLebecqueS 2011 Chikungunya virus envelope-specific human monoclonal antibodies with broad neutralization potency. J Immunol 186 3258 3264

29. GrobPSchijnsVEvan den BroekMFCoxSPAckermannM 1999 Role of the individual interferon systems and specific immunity in mice in controlling systemic dissemination of attenuated pseudorabies virus infection. J Virol 73 4748 4754

30. CoudercTChretienFSchilteCDissonOBrigitteM 2008 A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease. PLoS Pathog 4 e29

31. LawMHollinsheadRSmithGL 2002 Antibody-sensitive and antibody-resistant cell-to-cell spread by vaccinia virus: role of the A33R protein in antibody-resistant spread. J Gen Virol 83 209 222

32. MothesWShererNMJinJZhongP 2010 Virus cell-to-cell transmission. J Virol 84 8360 8368

33. SchroderCKeilGM 1999 Bovine herpesvirus 1 requires glycoprotein H for infectivity and direct spreading and glycoproteins gH(W450) and gB for glycoprotein D-independent cell-to-cell spread. J Gen Virol 80 Pt 1 57 61

34. SattentauQ 2008 Avoiding the void: cell-to-cell spread of human viruses. Nat Rev Microbiol 6 815 826

35. HahonNZimmermanWD 1970 Chikungunya virus infection of cell monolayers by cell-to-cell and extracellular transmission. Appl Microbiol 19 389 391

36. MeyerWJJohnstonRE 1993 Structural rearrangement of infecting Sindbis virions at the cell surface: mapping of newly accessible epitopes. J Virol 67 5117 5125

37. PenceDFDavisNLJohnstonRE 1990 Antigenic and genetic characterization of Sindbis virus monoclonal antibody escape mutants which define a pathogenesis domain on glycoprotein E2. Virology 175 41 49

38. StecDSWaddellASchmaljohnCSColeGASchmaljohnAL 1986 Antibody-selected variation and reversion in Sindbis virus neutralization epitopes. J Virol 57 715 720

39. VratiSFernonCADalgarnoLWeirRC 1988 Location of a major antigenic site involved in Ross River virus neutralization. Virology 162 346 353

40. AgapovEVRazumovIAFrolovIVKolykhalovAANetesovSV 1994 Localization of four antigenic sites involved in Venezuelan equine encephalomyelitis virus protection. Arch Virol 139 173 181

41. HuntARFredericksonSMaruyamaTRoehrigJTBlairCD 2010 The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity. PLoS Negl Trop Dis 4 e739

42. JohnsonBJBrubakerJRRoehrigJTTrentDW 1990 Variants of Venezuelan equine encephalitis virus that resist neutralization define a domain of the E2 glycoprotein. Virology 177 676 683

43. CoffeyLLVignuzziM 2011 Host alternation of chikungunya virus increases fitness while restricting population diversity and adaptability to novel selective pressures. J Virol 85 1025 1035

44. FlynnDCMeyerWJMackenzieJMJrJohnstonRE 1990 A conformational change in Sindbis virus glycoproteins E1 and E2 is detected at the plasma membrane as a consequence of early virus-cell interaction. J Virol 64 3643 3653

45. DrakeJWHollandJJ 1999 Mutation rates among RNA viruses. Proc Natl Acad Sci U S A 96 13910 13913

46. HollandJSpindlerKHorodyskiFGrabauENicholS 1982 Rapid evolution of RNA genomes. Science 215 1577 1585

47. SanjuanRNebotMRChiricoNManskyLMBelshawR 2010 Viral mutation rates. J Virol 84 9733 9748

48. CoffeyLLVasilakisNBraultACPowersAMTripetF 2008 Arbovirus evolution in vivo is constrained by host alternation. Proc Natl Acad Sci U S A 105 6970 6975

49. JerzakGBernardKAKramerLDEbelGD 2005 Genetic variation in West Nile virus from naturally infected mosquitoes and birds suggests quasispecies structure and strong purifying selection. J Gen Virol 86 2175 2183

50. WeaverSCRico-HesseRScottTW 1992 Genetic diversity and slow rates of evolution in New World alphaviruses. Curr Top Microbiol Immunol 176 99 117

51. TimpeJMStamatakiZJenningsAHuKFarquharMJ 2008 Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies. Hepatology 47 17 24

52. JohnsonDCHuberMT 2002 Directed egress of animal viruses promotes cell-to-cell spread. J Virol 76 1 8

53. BernardKAKlimstraWBJohnstonRE 2000 Mutations in the E2 glycoprotein of Venezuelan equine encephalitis virus confer heparan sulfate interaction, low morbidity, and rapid clearance from blood of mice. Virology 276 93 103

54. KlimstraWBRymanKDJohnstonRE 1998 Adaptation of Sindbis virus to BHK cells selects for use of heparan sulfate as an attachment receptor. J Virol 72 7357 7366

55. RymanKDGardnerCLBurkeCWMeierKCThompsonJM 2007 Heparan sulfate binding can contribute to the neurovirulence of neuroadapted and nonneuroadapted Sindbis viruses. J Virol 81 3563 3573

56. PlaskonNEAdelmanZNMylesKM 2009 Accurate strand-specific quantification of viral RNA. PLoS One 4 e7468