Heterogeneity and Breadth of Host Antibody Response to KSHV Infection Demonstrated by Systematic Analysis of the KSHV Proteome
Kaposi sarcoma-associated herpesvirus (KSHV) is the cause of Kaposi sarcoma, primary effusion lymphoma and a form of multicentric Castleman's disease, affecting mainly persons with HIV, other immunosuppressed patients and elderly men. Such diseases are most common where KSHV prevalence is high, in sub-Saharan Africa and the Mediterranean, and amongst men who have sex with men. Various assays for the serodiagnosis of KSHV have been developed to investigate global KSHV epidemiology. ELISAs utilizing one lytic (K8.1) and one latent antigen (ORF73) are often used. However, a more complete characterization of immune responses to all KSHV antigens may have important epidemiologic and clinical applications. We systematically expressed and purified 73 of the 85 proteins encoded by KSHV and analysed serologic responses in patients with KSHV-associated malignancies compared to healthy subjects. We identified significant reactivity to ORF38, ORF61, ORF59 and K5, in addition to the known K8.1, ORF73 and ORF65. Reactivity patterns were varied; however, HIV infected individuals were reactive to more antigens, with greater intensity. Next, we developed a bead-based assay that can test a small sample simultaneously for six KSHV antigens. The new tool can improve the detection of KSHV and the characterization of asymptomatic infection and KSHV associated diseases.
Vyšlo v časopise:
Heterogeneity and Breadth of Host Antibody Response to KSHV Infection Demonstrated by Systematic Analysis of the KSHV Proteome. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1004046
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004046
Souhrn
Kaposi sarcoma-associated herpesvirus (KSHV) is the cause of Kaposi sarcoma, primary effusion lymphoma and a form of multicentric Castleman's disease, affecting mainly persons with HIV, other immunosuppressed patients and elderly men. Such diseases are most common where KSHV prevalence is high, in sub-Saharan Africa and the Mediterranean, and amongst men who have sex with men. Various assays for the serodiagnosis of KSHV have been developed to investigate global KSHV epidemiology. ELISAs utilizing one lytic (K8.1) and one latent antigen (ORF73) are often used. However, a more complete characterization of immune responses to all KSHV antigens may have important epidemiologic and clinical applications. We systematically expressed and purified 73 of the 85 proteins encoded by KSHV and analysed serologic responses in patients with KSHV-associated malignancies compared to healthy subjects. We identified significant reactivity to ORF38, ORF61, ORF59 and K5, in addition to the known K8.1, ORF73 and ORF65. Reactivity patterns were varied; however, HIV infected individuals were reactive to more antigens, with greater intensity. Next, we developed a bead-based assay that can test a small sample simultaneously for six KSHV antigens. The new tool can improve the detection of KSHV and the characterization of asymptomatic infection and KSHV associated diseases.
Zdroje
1. ChangY, CesarmanE, PessinMS, LeeF, CulpepperJ, et al. (1994) Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 266: 1865–1869.
2. CesarmanE, NadorRG, AozasaK, DelsolG, SaidJW, et al. (1996) Kaposi's sarcoma-associated herpesvirus in non-AIDS related lymphomas occurring in body cavities. Am J Pathol 149: 53–57.
3. SoulierJ, GrolletL, OksenhendlerE, CacoubP, Cazals-HatemD, et al. (1995) Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood 86: 1276–1280.
4. de SanjoseS, MbisaG, Perez-AlvarezS, BenaventeY, SukvirachS, et al. (2009) Geographic Variation in the Prevalence of Kaposi Sarcoma-Associated Herpesvirus and Risk Factors for Transmission. J Infect Dis 199: 1449–1456.
5. MalopeBI, MacPhailP, MbisaG, MacPhailC, SteinL, et al. (2008) No evidence of sexual transmission of Kaposi's sarcoma herpes virus in a heterosexual South African population. Aids 22: 519–526.
6. Malope-KgokongBI, MacphailP, MbisaG, RatshikhophaE, MaskewM, et al. (2010) Kaposi's Sarcoma Associated-Herpes Virus (KSHV) Seroprevalence in Pregnant Women in South Africa. Infect Agent Cancer 5: 14.
7. WakehamK, WebbEL, SebinaI, MuhangiL, MileyW, et al. (2011) Parasite infection is associated with Kaposi's sarcoma associated herpesvirus (KSHV) in Ugandan women. Infect Agent Cancer 6: 15.
8. SerrainoD, TomaL, AndreoniM, ButtoS, TchangmenaO, et al. (2001) A seroprevalence study of human herpesvirus type 8 (HHV8) in eastern and Central Africa and in the Mediterranean area. Eur J Epidemiol 17: 871–876.
9. VitaleF, BriffaDV, WhitbyD, MaidaI, GrochowskaA, et al. (2001) Kaposi's sarcoma herpes virus and Kaposi's sarcoma in the elderly populations of 3 Mediterranean islands. Int J Cancer 91: 588–591.
10. WhitbyD, MarshallVA, BagniRK, WangCD, GamacheCJ, et al. (2004) Genotypic characterization of Kaposi's sarcoma-associated herpesvirus in asymptomatic infected subjects from isolated populations. J Gen Virol 85: 155–163.
11. de SouzaVA, SumitaLM, NascimentoMC, OliveiraJ, MascherettiM, et al. (2007) Human herpesvirus-8 infection and oral shedding in Amerindian and non-Amerindian populations in the Brazilian Amazon region. J Infect Dis 196: 844–852.
12. MartroE, EsteveA, SchulzTF, SheldonJ, GambusG, et al. (2007) Risk factors for human Herpesvirus 8 infection and AIDS-associated Kaposi's sarcoma among men who have sex with men in a European multicentre study. Int J Cancer 120: 1129–1135.
13. CasperC, WaldA, PaukJ, TabetSR, CoreyL, et al. (2002) Correlates of prevalent and incident Kaposi's sarcoma-associated herpesvirus infection in men who have sex with men. J Infect Dis 185: 990–993.
14. SmithNA, SabinCA, GopalR, BourbouliaD, LabbetW, et al. (1999) Serologic evidence of human herpesvirus 8 transmission by homosexual but not heterosexual sex. J Infect Dis 180: 600–606.
15. NascimentoMC, de SouzaVA, SumitaLM, FreireW, MunozF, et al. (2007) Comparative study of Kaposi's sarcoma-associated herpesvirus serological assays using clinically and serologically defined reference standards and latent class analysis. J Clin Microbiol 45: 715–720.
16. InoueN, MarEC, DollardSC, PauCP, ZhengQ, et al. (2000) New immunofluorescence assays for detection of Human herpesvirus 8-specific antibodies. Clin Diagn Lab Immunol 7: 427–435.
17. LamLL, PauCP, DollardSC, PellettPE, SpiraTJ (2002) Highly sensitive assay for human herpesvirus 8 antibodies that uses a multiple antigenic peptide derived from open reading frame K8.1. J Clin Microbiol 40: 325–329.
18. MbisaGL, MileyW, GamacheCJ, GilletteWK, EspositoD, et al. (2010) Detection of antibodies to Kaposi's sarcoma-associated herpesvirus: a new approach using K8.1 ELISA and a newly developed recombinant LANA ELISA. J Immunol Methods 356: 39–46.
19. BurbeloPD, LeahyHP, GrootS, BishopLR, MileyW, et al. (2009) Four-antigen mixture containing v-cyclin for serological screening of human herpesvirus 8 infection. Clin Vaccine Immunol 16: 621–627.
20. BurbeloPD, IssaAT, ChingKH, WyvillKM, LittleRF, et al. (2010) Distinct profiles of antibodies to Kaposi sarcoma-associated herpesvirus antigens in patients with Kaposi sarcoma, multicentric Castleman disease, and primary effusion lymphoma. The Journal of infectious diseases 201: 1919–1922.
21. CampbellTB, StaskusKA, FolkvordJ, WhiteIE, NeidJ, et al. (2005) Persistence of Kaposi sarcoma-associated herpesvirus (KSHV)-infected cells in KSHV/HIV-1-coinfected subjects without KSHV-associated diseases. J Infect Dis 191: 367–371.
22. MancusoR, BrambillaL, AgostiniS, BiffiR, HernisA, et al. (2011) Intrafamiliar transmission of Kaposi's sarcoma-associated herpesvirus and seronegative infection in family members of classic Kaposi's sarcoma patients. The Journal of general virology 92: 744–751.
23. LallemandF, DesireN, RozenbaumW, NicolasJC, MarechalV (2000) Quantitative analysis of human herpesvirus 8 viral load using a real- time PCR assay. J Clin Microbiol 38: 1404–1408.
24. SpiraTJ, LamL, DollardSC, MengYX, PauCP, et al. (2000) Comparison of serologic assays and PCR for diagnosis of human herpesvirus 8 infection. J Clin Microbiol 38: 2174–2180.
25. BiggarRJ, EngelsEA, WhitbyD, KedesDH, GoedertJJ (2003) Antibody reactivity to latent and lytic antigens to human herpesvirus-8 in longitudinally followed homosexual men. J Infect Dis 187: 12–18.
26. DollardSC, NelsonKE, NessPM, StambolisV, KuehnertMJ, et al. (2005) Possible transmission of human herpesvirus-8 by blood transfusion in a historical United States cohort. Transfusion 45: 500–503.
27. QuinlivanEB, WangRX, StewartPW, KolmoltriC, RegameyN, et al. (2001) Longitudinal sero-reactivity to human herpesvirus 8 (KSHV) in the Swiss HIV Cohort 4.7 years before KS. J Med Virol 64: 157–166.
28. MinhasV, CrabtreeKL, ChaoA, M'SokaTJ, KankasaC, et al. (2008) Early childhood infection by human herpesvirus 8 in Zambia and the role of human immunodeficiency virus type 1 coinfection in a highly endemic area. Am J Epidemiol 168: 311–320.
29. ZhengD, WanJ, ChoYG, WangL, ChiouCJ, et al. (2011) Comparison of humoral immune responses to Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus using a viral proteome microarray. The Journal of infectious diseases 204: 1683–1691.
30. PellettPE, WrightDJ, EngelsEA, AblashiDV, DollardSC, et al. (2003) Multicenter comparison of serologic assays and estimation of human herpesvirus 8 seroprevalence among US blood donors. Transfusion 43: 1260–1268.
31. RussoJJ, BohenzkyRA, ChienMC, ChenJ, YanM, et al. (1996) Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc Natl Acad Sci U S A 93: 14862–14867.
32. HopkinsR, EspositoD (2009) A rapid method for titrating baculovirus stocks using the Sf-9 Easy Titer cell line. BioTechniques 47: 785–788.
33. UldrickTS, WangV, O'MahonyD, AlemanK, WyvillKM, et al. (2010) An interleukin-6-related systemic inflammatory syndrome in patients co-infected with Kaposi sarcoma-associated herpesvirus and HIV but without Multicentric Castleman disease. Clin Infect Dis 51: 350–358.
34. ChandranB, BloomerC, ChanSR, ZhuL, GoldsteinE, et al. (1998) Human herpesvirus-8 ORF K8.1 gene encodes immunogenic glycoproteins generated by spliced transcripts. Virology 249: 140–149.
35. PiriouE, KimmelR, ChelimoK, MiddeldorpJM, OdadaPS, et al. (2009) Serological evidence for long-term Epstein-Barr virus reactivation in children living in a holoendemic malaria region of Kenya. J Med Virol 81: 1088–1093.
36. SchmittM, BravoIG, SnijdersPJ, GissmannL, PawlitaM, et al. (2006) Bead-based multiplex genotyping of human papillomaviruses. Journal of clinical microbiology 44: 504–512.
37. AlemayehuD, ZouKH (2012) Applications of ROC analysis in medical research: recent developments and future directions. Acad Radiol 19: 1457–1464.
38. SylwesterAW, MitchellBL, EdgarJB, TaorminaC, PelteC, et al. (2005) Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J Exp Med 202: 673–685.
39. JingL, HaasJ, ChongTM, BrucknerJJ, DannGC, et al. (2012) Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine. The Journal of clinical investigation 122: 654–673.
40. ChanSR, ChandranB (2000) Characterization of human herpesvirus 8 ORF59 protein (PF-8) and mapping of the processivity and viral DNA polymerase-interacting domains. J Virol 74: 10920–10929.
41. KatanoH, SataT, SudaT, NakamuraT, TachikawaN, et al. (1999) Expression and antigenicity of human herpesvirus 8 encoded ORF59 protein in AIDS-associated Kaposi's sarcoma. J Med Virol 59: 346–355.
42. PardieuC, ViganR, WilsonSJ, CalviA, ZangT, et al. (2010) The RING-CH Ligase K5 Antagonizes Restriction of KSHV and HIV-1 Particle Release by Mediating Ubiquitin-Dependent Endosomal Degradation of Tetherin. PLoS pathogens 6: e1000843.
43. IshidoS, WangC, LeeBS, CohenGB, JungJU (2000) Downregulation of major histocompatibility complex class I molecules by Kaposi's sarcoma-associated herpesvirus K3 and K5 proteins. J Virol 74: 5300–5309.
44. IshidoS, ChoiJK, LeeBS, WangC, DeMariaM, et al. (2000) Inhibition of natural killer cell-mediated cytotoxicity by Kaposi's sarcoma-associated herpesvirus K5 protein. Immunity 13: 365–374.
45. CoscoyL, GanemD (2001) A viral protein that selectively downregulates ICAM-1 and B7-2 and modulates T cell costimulation. J Clin Invest 107: 1599–1606.
46. LangSM, BynoeMO, KarkiR, TartellMA, MeansRE (2013) Kaposi's Sarcoma-Associated Herpesvirus K3 and K5 Proteins Down Regulate Both DC-SIGN and DC-SIGNR. PloS one 8: e58056.
47. PosavadCM, RemingtonM, MuellerDE, ZhaoL, MagaretAS, et al. (2010) Detailed characterization of T cell responses to herpes simplex virus-2 in immune seronegative persons. Journal of immunology 184: 3250–3259.
48. de JagerW, RijkersGT (2006) Solid-phase and bead-based cytokine immunoassay: a comparison. Methods 38: 294–303.
49. LaneyAS, DollardSC, JaffeHW, OffermannMK, SpiraTJ, et al. (2004) Repeated measures study of human herpesvirus 8 (HHV-8) DNA and antibodies in men seropositive for both HHV-8 and HIV. Aids 18: 1819–1826.
50. SitasF, CarraraH, BeralV, NewtonR, ReevesG, et al. (1999) Antibodies against human herpesvirus 8 in black South African patients with cancer. N Engl J Med 340: 1863–1871.
51. CannonMJ, DollardSC, BlackJB, EdlinBR, HannahC, et al. (2003) Risk factors for Kaposi's sarcoma in men seropositive for both human herpesvirus 8 and human immunodeficiency virus. Aids 17: 215–222.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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