#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Viral MicroRNA Effects on Pathogenesis of Polyomavirus SV40 Infections in Syrian Golden Hamsters


Effects of polyomavirus SV40 microRNA on pathogenesis of viral infections in vivo are not known. Syrian golden hamsters are the small animal model for studies of SV40. We report here effects of SV40 microRNA and influence of the structure of the regulatory region on dynamics of SV40 DNA levels in vivo. Outbred young adult hamsters were inoculated by the intracardiac route with 1×107 plaque-forming units of four different variants of SV40. Infected animals were sacrificed from 3 to 270 days postinfection and viral DNA loads in different tissues determined by quantitative real-time polymerase chain reaction assays. All SV40 strains displayed frequent establishment of persistent infections and slow viral clearance. SV40 had a broad tissue tropism, with infected tissues including liver, kidney, spleen, lung, and brain. Liver and kidney contained higher viral DNA loads than other tissues; kidneys were the preferred site for long-term persistent infection although detectable virus was also retained in livers. Expression of SV40 microRNA was demonstrated in wild-type SV40-infected tissues. MicroRNA-negative mutant viruses consistently produced higher viral DNA loads than wild-type SV40 in both liver and kidney. Viruses with complex regulatory regions displayed modestly higher viral DNA loads in the kidney than those with simple regulatory regions. Early viral transcripts were detected at higher levels than late transcripts in liver and kidney. Infectious virus was detected infrequently. There was limited evidence of increased clearance of microRNA-deficient viruses. Wild-type and microRNA-negative mutants of SV40 showed similar rates of transformation of mouse cells in vitro and tumor induction in weanling hamsters in vivo. This report identified broad tissue tropism for SV40 in vivo in hamsters and provides the first evidence of expression and function of SV40 microRNA in vivo. Viral microRNA dampened viral DNA levels in tissues infected by SV40 strains with simple or complex regulatory regions.


Vyšlo v časopise: Viral MicroRNA Effects on Pathogenesis of Polyomavirus SV40 Infections in Syrian Golden Hamsters. PLoS Pathog 10(2): e32767. doi:10.1371/journal.ppat.1003912
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003912

Souhrn

Effects of polyomavirus SV40 microRNA on pathogenesis of viral infections in vivo are not known. Syrian golden hamsters are the small animal model for studies of SV40. We report here effects of SV40 microRNA and influence of the structure of the regulatory region on dynamics of SV40 DNA levels in vivo. Outbred young adult hamsters were inoculated by the intracardiac route with 1×107 plaque-forming units of four different variants of SV40. Infected animals were sacrificed from 3 to 270 days postinfection and viral DNA loads in different tissues determined by quantitative real-time polymerase chain reaction assays. All SV40 strains displayed frequent establishment of persistent infections and slow viral clearance. SV40 had a broad tissue tropism, with infected tissues including liver, kidney, spleen, lung, and brain. Liver and kidney contained higher viral DNA loads than other tissues; kidneys were the preferred site for long-term persistent infection although detectable virus was also retained in livers. Expression of SV40 microRNA was demonstrated in wild-type SV40-infected tissues. MicroRNA-negative mutant viruses consistently produced higher viral DNA loads than wild-type SV40 in both liver and kidney. Viruses with complex regulatory regions displayed modestly higher viral DNA loads in the kidney than those with simple regulatory regions. Early viral transcripts were detected at higher levels than late transcripts in liver and kidney. Infectious virus was detected infrequently. There was limited evidence of increased clearance of microRNA-deficient viruses. Wild-type and microRNA-negative mutants of SV40 showed similar rates of transformation of mouse cells in vitro and tumor induction in weanling hamsters in vivo. This report identified broad tissue tropism for SV40 in vivo in hamsters and provides the first evidence of expression and function of SV40 microRNA in vivo. Viral microRNA dampened viral DNA levels in tissues infected by SV40 strains with simple or complex regulatory regions.


Zdroje

1. Imperiale MJ, Major EO (2007) Polyomaviruses. In: Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA et al.., editors. Fields Virology. Philadelphia: Lippincott Williams & Wilkins. pp. 2263–2298.

2. Butel JS (2012) Polyomavirus SV40: model infectious agent of cancer. In: Robertson E, editors. Cancer Associated Viruses. Springer Science. pp. 377–417.

3. PipasJM (2009) SV40: Cell transformation and tumorigenesis. Virology 384: 294–303.

4. GjoerupO, ChangY (2010) Update on human polyomaviruses and cancer. Adv Cancer Res 106: 1–51.

5. ButelJS (2000) Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease. Carcinogenesis 21: 405–426.

6. JavierRT, ButelJS (2008) The history of tumor virology. Cancer Res 68: 7693–7706.

7. AhujaD, Sáenz-RoblesMT, PipasJM (2005) SV40 large T antigen targets multiple cellular pathways to elicit cellular transformation. Oncogene 24: 7729–7745.

8. BruggeJS, ButelJS (1975) Role of simian virus 40 gene A function in maintenance of transformation. J Virol 15: 619–635.

9. ButelJS, TevethiaSS, MelnickJL (1972) Oncogenicity and cell transformation by papovavirus SV40: The role of the viral genome. Adv Cancer Res 15: 1–55.

10. SwainJL, SrollerV, WongC, ZhangS, HalvorsonSJ, et al. (2012) Effects of route of inoculation and viral genetic variation on antibody responses to polyomavirus SV40 in Syrian golden hamsters. Comp Med 62: 400–408.

11. CicalaC, PompettiF, CarboneM (1993) SV40 induces mesotheliomas in hamsters. Am J Pathol 142: 1524–1533.

12. DiamandopoulosGT (1973) Induction of lymphocytic leukemia, lymphosarcoma, reticulum cell sarcoma, and osteogenic sarcoma in the Syrian golden hamster by oncogenic DNA simian virus 40. J Natl Cancer Inst 50: 1347–1365.

13. GirardiAJ, SweetBH, SlotnickVB, HillemanMR (1962) Development of tumors in hamsters inoculated in the neonatal period with vacuolating virus, SV40. Proc Soc Exp Biol Med 109: 649–660.

14. McNeesAL, VilchezRA, HeardTC, SrollerV, WongC, et al. (2009) SV40 lymphomagenesis in Syrian golden hamsters. Virology 384: 114–124.

15. PatelNC, HalvorsonSJ, SrollerV, ArringtonAS, WongC, et al. (2009) Viral regulatory region effects on vertical transmission of polyomavirus SV40 in hamsters. Virology 386: 94–101.

16. SrollerV, VilchezRA, StewartAR, WongC, ButelJS (2008) Influence of the viral regulatory region on tumor induction by simian virus 40 in hamsters. J Virol 82: 871–879.

17. VilchezRA, BraytonCF, WongC, ZanwarP, KillenDE, et al. (2004) Differential ability of two simian virus 40 strains to induce malignancies in weanling hamsters. Virology 330: 168–177.

18. UmbachJL, CullenBR (2009) The role of RNAi and microRNAs in animal virus replication and antiviral immunity. Genes Dev 23: 1151–1164.

19. GrundhoffA, SullivanCS (2011) Virus-encoded microRNAs. Virology 411: 325–343.

20. SullivanCS, GrundhoffAT, TevethiaS, PipasJM, GanemD (2005) SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells. Nature 435: 682–686.

21. VilchezRA, MaddenCR, KozinetzCA, HalvorsonSJ, WhiteZS, et al. (2002) Association between simian virus 40 and non-Hodgkin lymphoma. Lancet 359: 817–823.

22. ButelJS (2012) Patterns of polyomavirus SV40 infections and associated cancers in humans: a model. Curr Opin Virol 2: 508–514.

23. PatelNC, VilchezRA, KillenDE, ZanwarP, SrollerV, et al. (2008) Detection of polyomavirus SV40 in tonsils from immunocompetent children. J Clin Virol 43: 66–72.

24. ToracchioS, KozinetzCA, KillenDE, SheehanAM, BanezEI, et al. (2009) Variable frequency of polyomavirus SV40 and herpesvirus EBV in lymphomas from two different urban population groups in Houston, TX. J Clin Virol 46: 154–160.

25. Butel JS (2010) Simian virus 40, human infections, and cancer: emerging concepts and causality considerations. In: Khalili K, Jeang KT, editors. Viral Oncology: Basic Science and Clinical Applications. Hoboken, NJ: Wiley-Blackwell. pp. 165–189.

26. ParacchiniV, GarteS, PedottiP, PoliF, FrisonS, et al. (2005) Molecular identification of simian virus 40 infection in healthy Italian subjects by birth cohort. Mol Med 11: 48–51.

27. SeoGJ, FinkLHL, O'HaraB, AtwoodWJ, SullivanCS (2008) Evolutionarily conserved function of a viral microRNA. J Virol 82: 9823–9828.

28. SeoGJ, ChenCJ, SullivanCS (2009) Merkel cell polyomavirus encodes a microRNA with the ability to autoregulate viral gene expression. Virology 383: 183–187.

29. SullivanCS, SungCK, PackCD, GrundhoffA, LukacherAE, et al. (2009) Murine Polyomavirus encodes a microRNA that cleaves early RNA transcripts but is not essential for experimental infection. Virology 387: 157–167.

30. CullenBR (2013) MicroRNAs as mediators of viral evasion of the immune system. Nat Immunol 14: 205–210.

31. BossIW, RenneR (2011) Viral miRNAs and immune evasion. Biochim Biophys Acta 1809: 708–714.

32. GottweinE (2012) Kaposi's sarcoma-associated herpesvirus microRNAs. Front Microbiol 3: e165.

33. BarthS, MeisterG, GrässerFA (2011) EBV-encoded miRNAs. Biochim Biophys Acta 1809: 631–640.

34. KincaidRP, SullivanCS (2012) Virus-encoded microRNAs: an overview and a look to the future. PLoS Pathogens 8: e1003018.

35. LednickyJA, WongC, ButelJS (1995) Artificial modification of the viral regulatory region improves tissue culture growth of SV40 strain 776. Virus Res 35: 143–153.

36. LednickyJA, ButelJS (2001) Simian virus 40 regulatory region structural diversity and the association of viral archetypal regulatory regions with human brain tumors. Semin Cancer Biol 11: 39–47.

37. BroekemaNM, ImperialeMJ (2012) Efficient propagation of archetype BK and JC polyomaviruses. Virology 422: 235–241.

38. LednickyJA, ArringtonAS, StewartAR, DaiXM, WongC, et al. (1998) Natural isolates of simian virus 40 from immunocompromised monkeys display extensive genetic heterogeneity: New implications for polyomavirus disease. J Virol 72: 3980–3990.

39. TavazziE, WhiteMK, KhaliliK (2012) Progressive multifocal leukoencephalopathy: clinical and molecular aspects. Rev Med Virol 22: 18–32.

40. GosertR, KardasP, MajorEO, HirschHH (2010) Rearranged JC virus noncoding control regions found in progressive multifocal leukoencephalopathy patient samples increase virus early gene expression and replication rate. J Virol 84: 10448–10456.

41. NakamichiK, KishidaS, TanakaK, SuganumaA, SanoY, et al. (2013) Sequential changes in the non-coding control region sequences of JC polyomaviruses from the cerebrospinal fluid of patients with progressive multifocal leukoencephalopathy. Arch Virol 158: 639–650.

42. GosertR, RinaldoCH, FunkGA, EgliA, RamosE, et al. (2008) Polyomavirus BK with rearranged noncoding control region emerge in vivo in renal transplant patients and increase viral replication and cytopathology. J Exp Med 205: 841–852.

43. ForsmanZH, LednickyJA, FoxGE, WillsonRC, WhiteZS, et al. (2004) Phylogenetic analysis of polyomavirus simian virus 40 from monkeys and humans reveals genetic variation. J Virol 78: 9306–9316.

44. StewartAR, LednickyJA, BenzickUS, TevethiaMJ, ButelJS (1996) Identification of a variable region at the carboxy terminus of SV40 large T-antigen. Virology 221: 355–361.

45. BroekemaNM, ImperialeMJ (2013) miRNA regulation of BK polyomavirus replication during early infection. Proc Natl Acad Sci USA 110: 8200–8205.

46. BaumanY, NachmaniD, VitenshteinA, TsukermanP, DraymanN, et al. (2011) An identical miRNA of the human JC and BK polyoma viruses targets the stress-induced ligand ULBP3 to escape immune elimination. Cell Host Microbe 9: 93–102.

47. ThomasMA, SpencerJF, La ReginaMC, DharD, TollefsonAE, et al. (2006) Syrian hamster as a permissive immunocompetent animal model for the study of oncolytic adenovirus vectors. Cancer Res 66: 1270–1276.

48. GowenBB, BarnardDL, SmeeDF, WongMH, PaceAM, et al. (2005) Interferon alfacon-1 protects hamsters from lethal Pichinde virus infection. Antimicrob Agents Chemother 49: 2378–2386.

49. TeshRB, SiirinM, GuzmanH, Travassos da RosaAPA, WuX, et al. (2005) Persistent West Nile virus infection in the golden hamster: Studies on its mechanism and possible implications for other flavivirus infections. J Infect Dis 192: 287–295.

50. SiirinMT, DuanT, LeiH, GuzmanH, Travassos da RosaAPA, et al. (2007) Chronic St. Louis encephalitis virus infection in the golden hamster (Mesocricetus auratus). Am J Trop Med Hyg 76: 200–306.

51. CampenMJ, MilazzoML, FulhorstCF, AkataCJO, KosterF (2006) Characterization of shock in a hamster model of hantavirus infection. Virology 356: 45–49.

52. van EkdomLT, HerbrinkP, MeddensMJ (1987) Hamster model for herpes simplex virus infection of the central nervous system. Infection 15: 125–127.

53. VanchiereJA, BelliniWJ, MoyerSA (1995) Hypermutation of the phosphoprotein and altered mRNA editing in the hamster neurotropic strain of measles virus. Virology 207: 555–561.

54. WongKT, GrosjeanI, BrissonC, BlanquierB, Fevre-MontangeM, et al. (2003) A golden hamster model for human acute Nipah virus infection. Am J Pathol 163: 2127–2137.

55. RayfieldEJ, KellyKJ, YoonJW (1986) Rubella virus-induced diabetes in the hamster. Diabetes 35: 1278–1281.

56. MelbyPC, ChandrasekarB, ZhaoW, CoeJE (2001) The hamster as a model of human visceral leishmaniasis: Progressive disease and impaired generation of nitric oxide in the face of a prominent Th1-like cytokine response. J Immunol 166: 1912–1920.

57. Institute for Laboratory Animal Research (1996) Guide for the Care and Use of Laboratory Animals. Washington, D.C.: National Academies Press.

58. SweetBH, HillemanMR (1960) The vacuolating virus, S.V.40. Proc Soc Exp Biol Med 105: 420–427.

59. LednickyJA, GarceaRL, BergsagelDJ, ButelJS (1995) Natural simian virus 40 strains are present in human choroid plexus and ependymoma tumors. Virology 212: 710–717.

60. ArringtonAS, MooreMS, ButelJS (2004) SV40-positive brain tumor in scientist with risk of laboratory exposure to the virus. Oncogene 23: 2231–2235.

61. KriegP, SchererG (1984) Cloning of SV40 genomes from human brain tumors. Virology 138: 336–340.

62. CutroneR, LednickyJ, DunnG, RizzoP, BocchettaM, et al. (2005) Some oral poliovirus vaccines were contaminated with infectious SV40 after 1961. Cancer Res 65: 10273–10279.

63. ButelJS, JafarS, WongC, ArringtonAS, OpekunAR, et al. (1999) Evidence of SV40 infections in hospitalized children. Hum Pathol 30: 1496–1502.

64. McNeesAL, WhiteZS, ZanwarP, VilchezRA, ButelJS (2005) Specific and quantitative detection of human polyomaviruses BKV, JCV, and SV40 by real time PCR. J Clin Virol 34: 52–62.

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2014 Číslo 2
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#