DOI QR코드

DOI QR Code

Characterization of Prototype Foamy Virus Infectivity in Transportin 3 Knockdown Human 293t Cell Line

  • Hamid, Faysal Bin (Department of Systems Biotechnology, Chung-Ang University) ;
  • Kim, Jinsun (Department of Systems Biotechnology, Chung-Ang University) ;
  • Shin, Cha-Gyun (Department of Systems Biotechnology, Chung-Ang University)
  • Received : 2016.06.08
  • Accepted : 2016.11.12
  • Published : 2017.02.28

Abstract

The foamy viruses are currently considered essential for development as vectors for gene delivery. Previous studies demonstrated that prototype foamy virus (PFV) can infect and replicate prevalently in a variety of cell types for its exclusive replication strategy. However, the virus-host interaction, especially PFV-transportin3 (TNPO3), is still poorly understood. In our investigation of the role of TNPO3 in PFV infection, we found lower virus production in TNPO3 knockdown (KD) cells compared with wild-type 293T cells. PCR analysis revealed that viral DNAs were mostly altered to circular forms: both 1-long terminal repeat (1-LTR) and 2-LTR in TNPO3 KD cells. We therefore suggest that TNPO3 is required for successful PFV replication, at least at/after the nuclear entry step of viral DNA. These findings highlight the obscure mysteries of PFV-host interaction and the requirement of TNPO3 for productive infection of PFV in 293T cells.

Keywords

References

  1. Bodem J, Lochelt M, Winkler I, Flower RP, Delius H, Flugel RM. 1996. Characterization of the spliced pol transcript of feline foamy virus: the splice acceptor site of the pol transcript is located in gag of foamy viruses. J. Virol. 70: 9024.
  2. Callahan ME, Switzer WM, Matthews AL, Roberts BD, Heneine W, Folks TM, et al. 1999. Persistent zoonotic infection of a human with simian foamy virus in the absence of an intact orf-2 accessory gene. J. Virol. 73: 9619-9624.
  3. Erlwein O, McClure MO, 2010. Progress and prospects: foamy virus vectors enter a new age. Gene Ther. 17: 1423-1429. https://doi.org/10.1038/gt.2010.95
  4. Schweizer M, Turek R, Hahn H, Schliephake A, Netzer KO, Eder G, et al. 1995. Markers of foamy virus infections in monkeys, apes, and accidentally infected humans: appropriate testing fails to confirm suspected foamy virus prevalence in humans. AIDS Res. Hum. Retroviruses 11: 161-170. https://doi.org/10.1089/aid.1995.11.161
  5. Keshet E, Temin HM. 1979. Cell killing by spleen necrosis virus is correlated with a transient accumulation of spleen necrosis virus DNA. J. Virol. 31: 376-388.
  6. Achong BG, Mansell PW, Epstein MA, Clifford P. 1971. An unusual virus in cultures from a human nasopharyngeal carcinoma. J. Natl. Cancer Inst. 46: 299-307.
  7. Hill CL, Bieniasz PD, McClure MO. 1999. Properties of human foamy virus relevant to its development as a vector for gene therapy. J. Gen. Virol. 80: 2003-2009. https://doi.org/10.1099/0022-1317-80-8-2003
  8. Brass AL, Dykxhoorn DM, Benita Y, Yan N, Engelman A, Xavier RJ, et al. 2008. Identification of host proteins required for HIV infection through a functional genomic screen. Science 319: 921-926. https://doi.org/10.1126/science.1152725
  9. Christ F, Thys W, De Rijck J, Gijsbers R, Albanese A, Arosio D, et al. 2008. Transportin-SR2 imports HIV into the nucleus. Curr. Biol. 18: 1192-1202. https://doi.org/10.1016/j.cub.2008.07.079
  10. König R, Zhou Y, Elleder D, Diamond TL, Bonamy GM, Irelan JT, et al. 2008. Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. Cell 135: 49-60. https://doi.org/10.1016/j.cell.2008.07.032
  11. Shah VB, Shi J, Hout DR, Oztop I, Krishnan L, Ahn J, et al. 2013. The host proteins transportin SR2/TNPO3 and cyclophilin A exert opposing effects on HIV-1 uncoating. J. Virol. 87: 422-432. https://doi.org/10.1128/JVI.07177-11
  12. Cribier A, Segeral E, Delelis O, Parissi V, Simon A, Ruff M, et al. 2011. Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import. Retrovirology 8: 104. https://doi.org/10.1186/1742-4690-8-104
  13. De Iaco A, Santoni F, Vannier A, Guipponi M, Antonarakis S, Luban J. 2013. TNPO3 protects HIV-1 replication from CPSF6-mediated capsid stabilization in the host cell cytoplasm. Retrovirology 10: 20. https://doi.org/10.1186/1742-4690-10-20
  14. Valle-Casuso JC, Di Nunzio F, Yang Y, Reszka N, Lienlaf M, Arhel N, et al. 2012. TNPO3 is required for HIV-1 replication after nuclear import but prior to integration and binds the HIV-1 core. J. Virol. 86: 5931-5936. https://doi.org/10.1128/JVI.00451-12
  15. Krishnan L, Matreyek KA, Oztop I, Lee K, Tipper CH, Li X, et al. 2010. The requirement for cellular transportin 3 (TNPO3 or TRN-SR2) during infection maps to human immunodeficiency virus type 1 capsid and not integrase. J. Virol. 84: 397-406. https://doi.org/10.1128/JVI.01899-09
  16. Patton GS, Erlwein O, McClure MO. 2004. Cell-cycle dependence of foamy virus vectors. J. Gen. Virol. 85: 2925-2930. https://doi.org/10.1099/vir.0.80210-0
  17. Imrich H, Heinkelein M, Herchenro der O, Rethwilm A. 2000. Primate foamy virus Pol proteins are imported into the nucleus. J. Gen. Virol. 81: 2941-2947. https://doi.org/10.1099/0022-1317-81-12-2941
  18. Saib A, Puvion-Dutilleul F, Schmid M, Peries J, de The H. 1997. Nuclear targeting of incoming human foamy virus Gag proteins involves a centriolar step. J. Virol. 71: 1155-1161.
  19. Ali MK, Kim J, Hamid FB, Shin CG. 2015. Knockdown of the host cellular protein transportin 3 attenuates prototype foamy virus infection. Biosci. Biotechnol. Biochem. 9: 1-9.
  20. Moebes A, Enssle J, Bieniasz PD, Heinkelein M, Lindemann D, Bock M, et al. 1997. Human foamy virus reverse transcription that occurs late in the viral replication cycle. J. Virol. 71: 7305-7311
  21. Yu SF, Sullivan MD, Linial ML. 1999. Evidence that the human foamy virus genome is DNA. J. Virol. 73: 1565-1572.
  22. Lee HS, Kang SY, Shin CG. 2005. Characterization of the functional domains of human foamy virus integrase using chimeric integrases. Mol. Cells 19: 246-255.
  23. Mullers E, Stirnnagel K, Kaulfuss S, Lindemann D. 2011. Prototype foamy virus Gag nuclear localization: a novel pathway among retroviruses. J. Virol. 85: 9276-9285. https://doi.org/10.1128/JVI.00663-11
  24. Yu SF, Linial ML. 1993. Analysis of the role of the bel and bet open reading frames of human foamy virus by using a new quantitative assay. J. Virol. 67: 6618-6624.
  25. Armand-Ugon M, Gutierrez A, Clotet B, Este JA. 2003. HIV-1 resistance to the gp41-dependent fusion inhibitor C-34. Antivir. Res. 59: 137-142. https://doi.org/10.1016/S0166-3542(03)00071-8
  26. Hossain A, Ali K, Shin CG. 2014. Nuclear localization signals in prototype foamy viral integrase for successive infection and replication in dividing cells. Mol. Cells 37: 140-148. https://doi.org/10.14348/molcells.2014.2331
  27. Freed EO, Martin MA. 1996. Domains of the human immunodeficiency virus type 1 matrix and gp41 cytoplasmic tail required for envelope incorporation into virions. J. Virol. 70: 341-351.
  28. Ribeiro-Romao RP, Saavedra AF, De-Cruz AM, Pinto EF, Moreira OC. 2016. Development of real-time PCR assays for evaluation of immune response and parasite load in golden hamster infected by Leishamnia braziliensis. Parasit. Vectors 9: 361-372. https://doi.org/10.1186/s13071-016-1647-6
  29. Henderson BR, Percipalle P. 1997. Interactions between HIV Rev and nuclear import and export factors: the Rev nuclear localization signal mediates specific binding to human importin-beta. J. Mol. Biol. 274: 693-707. https://doi.org/10.1006/jmbi.1997.1420
  30. Matreyek KA, Engelman A. 2013. Viral and cellular requirements for the nuclear entry of retroviral preintegration nucleoprotein complexes. Viruses 5: 2483-2511. https://doi.org/10.3390/v5102483
  31. Truant R, Cullen BR. 1999. The arginine rich domains present in human immunodeficiency virus type 1 Tat and Rev function as direct importin beta-dependent nuclear localization signals. Mol. Cell. Biol. 19: 1210-1217. https://doi.org/10.1128/MCB.19.2.1210
  32. Schaller T, Ocwieja KE, Rasaiyaah J, Price AJ, Brady TL, Roth SL, et al. 2011. HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. PLoS Pathog. 7: e1002439. https://doi.org/10.1371/journal.ppat.1002439
  33. Kilzer JM, Stracker T, Beitzel B, Meek K, Weitzman M, Bushman FD. 2003. Roles of host cell factors in circularization of retroviral DNA. Virology 314: 460-467. https://doi.org/10.1016/S0042-6822(03)00455-0

Cited by

  1. Hepatitis E Virus Methyltransferase Inhibits Type I Interferon Induction by Targeting RIG-I vol.28, pp.9, 2017, https://doi.org/10.4014/jmb.1808.08058
  2. Hepatitis E Virus Papain-Like Cysteine Protease Inhibits Type I Interferon Induction by Down-Regulating Melanoma Differentiation-Associated Gene 5 vol.28, pp.11, 2017, https://doi.org/10.4014/jmb.1809.09028
  3. Roles of Protein Histidine Phosphatase 1 (PHPT1) in Brown Adipocyte Differentiation vol.30, pp.2, 2017, https://doi.org/10.4014/jmb.1909.09003
  4. Foamy Virus Integrase in Development of Viral Vector for Gene Therapy vol.30, pp.9, 2017, https://doi.org/10.4014/jmb.2003.03046
  5. Role of Transportin-SR2 in HIV-1 Nuclear Import vol.13, pp.5, 2017, https://doi.org/10.3390/v13050829