The herpes simplex virus host shutoff (vhs) RNase limits accumulation of double stranded RNA in infected cells: Evidence for accelerated decay of duplex RNA

Autoři: Bianca Dauber aff001;  Holly A. Saffran aff001;  James R. Smiley aff001
Působiště autorů: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada aff001
Vyšlo v časopise: The herpes simplex virus host shutoff (vhs) RNase limits accumulation of double stranded RNA in infected cells: Evidence for accelerated decay of duplex RNA. PLoS Pathog 15(10): e32767. doi:10.1371/journal.ppat.1008111
Kategorie: Research Article


The herpes simplex virus virion host shutoff (vhs) RNase destabilizes cellular and viral mRNAs and blunts host innate antiviral responses. Previous work demonstrated that cells infected with vhs mutants display enhanced activation of the host double-stranded RNA (dsRNA)-activated protein kinase R (PKR), implying that vhs limits dsRNA accumulation in infected cells. Confirming this hypothesis, we show that partially complementary transcripts of the UL23/UL24 and UL30/31 regions of the viral genome increase in abundance when vhs is inactivated, giving rise to greatly increased levels of intracellular dsRNA formed by annealing of the overlapping portions of these RNAs. Thus, vhs limits accumulation of dsRNA at least in part by reducing the levels of complementary viral transcripts. We then asked if vhs also destabilizes dsRNA after its initial formation. Here, we used a reporter system employing two mCherry expression plasmids bearing complementary 3’ UTRs to produce defined dsRNA species in uninfected cells. The dsRNAs are unstable, but are markedly stabilized by co-expressing the HSV dsRNA-binding protein US11. Strikingly, vhs delivered by super-infecting HSV virions accelerates the decay of these pre-formed dsRNAs in both the presence and absence of US11, a novel and unanticipated activity of vhs. Vhs binds the host RNA helicase eIF4A, and we find that vhs-induced dsRNA decay is attenuated by the eIF4A inhibitor hippuristanol, providing evidence that eIF4A participates in the process. Our results show that a herpesvirus host shutoff RNase destabilizes dsRNA in addition to targeting partially complementary viral mRNAs, raising the possibility that the mRNA destabilizing proteins of other viral pathogens dampen the host response to dsRNA through similar mechanisms.

Klíčová slova:

HeLa cells – Messenger RNA – Ribonucleases – RNA annealing – RNA extraction – Virions – dsRNA viruses – Double stranded RNA


1. Sparrer KM, Gack MU. Intracellular detection of viral nucleic acids. Curr Opin Microbiol. 2015;26:1–9. Epub 2015/03/22. doi: 10.1016/j.mib.2015.03.001 25795286; PubMed Central PMCID: PMC5084527.

2. Chan YK, Gack MU. Viral evasion of intracellular DNA and RNA sensing. Nature reviews Microbiology. 2016;14(6):360–73. Epub 2016/05/14. doi: 10.1038/nrmicro.2016.45 27174148; PubMed Central PMCID: PMC5072394.

3. Dauber B, Wolff T. Activation of the Antiviral Kinase PKR and Viral Countermeasures. Viruses. 2009;1(3):523–44. Epub 2009/12/01. doi: 10.3390/v1030523 21994559; PubMed Central PMCID: PMC3185532.

4. Garcia MA, Gil J, Ventoso I, Guerra S, Domingo E, Rivas C, et al. Impact of protein kinase PKR in cell biology: from antiviral to antiproliferative action. Microbiol Mol Biol Rev. 2006;70(4):1032–60. doi: 10.1128/MMBR.00027-06 17158706; PubMed Central PMCID: PMC1698511.

5. Paladino P, Mossman KL. Mechanisms employed by herpes simplex virus 1 to inhibit the interferon response. Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research. 2009;29(9):599–607. Epub 2009/08/22. doi: 10.1089/jir.2009.0074 19694546.

6. Cassady KA, Gross M, Roizman B. The herpes simplex virus US11 protein effectively compensates for the gamma1(34.5) gene if present before activation of protein kinase R by precluding its phosphorylation and that of the alpha subunit of eukaryotic translation initiation factor 2. Journal of virology. 1998;72(11):8620–6. Epub 1998/10/10. 9765401; PubMed Central PMCID: PMC110273.

7. Mulvey M, Poppers J, Ladd A, Mohr I. A herpesvirus ribosome-associated, RNA-binding protein confers a growth advantage upon mutants deficient in a GADD34-related function. Journal of virology. 1999;73(4):3375–85. Epub 1999/03/12. 10074192; PubMed Central PMCID: PMC104102.

8. Poppers J, Mulvey M, Khoo D, Mohr I. Inhibition of PKR activation by the proline-rich RNA binding domain of the herpes simplex virus type 1 Us11 protein. Journal of virology. 2000;74(23):11215–21. Epub 2000/11/09. doi: 10.1128/jvi.74.23.11215-11221.2000 11070019; PubMed Central PMCID: PMC113216.

9. Peters GA, Khoo D, Mohr I, Sen GC. Inhibition of PACT-mediated activation of PKR by the herpes simplex virus type 1 Us11 protein. Journal of virology. 2002;76(21):11054–64. Epub 2002/10/09. doi: 10.1128/JVI.76.21.11054-11064.2002 12368348; PubMed Central PMCID: PMC136652.

10. Sanchez R, Mohr I. Inhibition of cellular 2'-5' oligoadenylate synthetase by the herpes simplex virus type 1 Us11 protein. Journal of virology. 2007;81(7):3455–64. Epub 2007/01/19. doi: 10.1128/JVI.02520-06 17229694; PubMed Central PMCID: PMC1866071.

11. Xing J, Wang S, Lin R, Mossman KL, Zheng C. Herpes simplex virus 1 tegument protein US11 downmodulates the RLR signaling pathway via direct interaction with RIG-I and MDA-5. Journal of virology. 2012;86(7):3528–40. Epub 2012/02/04. doi: 10.1128/JVI.06713-11 22301138; PubMed Central PMCID: PMC3302539.

12. He B, Gross M, Roizman B. The γ134.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. Proceedings of the National Academy of Sciences. 1997;94(3):843–8.

13. Sciortino MT, Parisi T, Siracusano G, Mastino A, Taddeo B, Roizman B. The virion host shutoff RNase plays a key role in blocking the activation of protein kinase R in cells infected with herpes simplex virus 1. Journal of virology. 2013;87(6):3271–6. Epub 2013/01/11. doi: 10.1128/JVI.03049-12 23302873; PubMed Central PMCID: PMC3592158.

14. Dauber B, Poon D, Dos Santos T, Duguay BA, Mehta N, Saffran HA, et al. The Herpes Simplex Virus Virion Host Shutoff Protein Enhances Translation of Viral True Late mRNAs Independently of Suppressing Protein Kinase R and Stress Granule Formation. Journal of virology. 2016;90(13):6049–57. doi: 10.1128/JVI.03180-15 27099317; PubMed Central PMCID: PMC4907241.

15. Read GS. Virus-encoded endonucleases: expected and novel functions. Wiley interdisciplinary reviews RNA. 2013;4(6):693–708. Epub 2013/08/01. doi: 10.1002/wrna.1188 23900973.

16. Smiley JR. Herpes Simplex Virus Virion Host Shutoff Protein: Immune Evasion Mediated by a Viral RNase? Journal of virology. 2004;78(3):1063–8. doi: 10.1128/JVI.78.3.1063-1068.2004 14722261

17. Abernathy E, Glaunsinger B. Emerging roles for RNA degradation in viral replication and antiviral defense. Virology. 2015;479–480:600–8. doi: 10.1016/j.virol.2015.02.007 25721579; PubMed Central PMCID: PMC4424162.

18. Gaglia MM, Covarrubias S, Wong W, Glaunsinger BA. A common strategy for host RNA degradation by divergent viruses. Journal of virology. 2012;86(17):9527–30. Epub 2012/06/29. doi: 10.1128/JVI.01230-12 22740404; PubMed Central PMCID: PMC3416159.

19. Rivas HG, Schmaling SK, Gaglia MM. Shutoff of Host Gene Expression in Influenza A Virus and Herpesviruses: Similar Mechanisms and Common Themes. Viruses. 2016;8(4):102. doi: 10.3390/v8040102 27092522; PubMed Central PMCID: PMC4848596.

20. Glaunsinger BA. Modulation of the Translational Landscape During Herpesvirus Infection. Annu Rev Virol. 2015;2(1):311–33. doi: 10.1146/annurev-virology-100114-054839 26958918; PubMed Central PMCID: PMC4921129.

21. Page HG, Read GS. The virion host shutoff endonuclease (UL41) of herpes simplex virus interacts with the cellular cap-binding complex eIF4F. Journal of virology. 2010;84(13):6886–90. doi: 10.1128/JVI.00166-10 20427534; PubMed Central PMCID: PMC2903273.

22. Doepker RC, Hsu W-L, Saffran HA, Smiley JR. Herpes Simplex Virus Virion Host Shutoff Protein Is Stimulated by Translation Initiation Factors eIF4B and eIF4H. Journal of virology. 2004;78(9):4684–99. doi: 10.1128/JVI.78.9.4684-4699.2004 15078951

23. Feng P, Everly DN, Read GS. mRNA Decay during Herpes Simplex Virus (HSV) Infections: Protein-Protein Interactions Involving the HSV Virion Host Shutoff Protein and Translation Factors eIF4H and eIF4A. Journal of virology. 2005;79(15):9651–64. doi: 10.1128/JVI.79.15.9651-9664.2005 16014927

24. Feng P, Everly DN Jr., Read GS. mRNA decay during herpesvirus infections: interaction between a putative viral nuclease and a cellular translation factor. Journal of virology. 2001;75(21):10272–80. doi: 10.1128/JVI.75.21.10272-10280.2001 11581395; PubMed Central PMCID: PMC114601.

25. Shiflett LA, Read GS. mRNA decay during herpes simplex virus (HSV) infections: mutations that affect translation of an mRNA influence the sites at which it is cleaved by the HSV virion host shutoff (Vhs) protein. Journal of virology. 2013;87(1):94–109. Epub 2012/10/19. doi: 10.1128/JVI.01557-12 23077305; PubMed Central PMCID: PMC3536374.

26. Oroskar AA, Read GS. Control of mRNA stability by the virion host shutoff function of herpes simplex virus. Journal of virology. 1989;63(5):1897–906. 2539493

27. Kwong AD, Frenkel N. Herpes simplex virus-infected cells contain a function(s) that destabilizes both host and viral mRNAs. Proceedings of the National Academy of Sciences. 1987;84(7):1926–30.

28. Oroskar AA, Read GS. A mutant of herpes simplex virus type 1 exhibits increased stability of immediate-early (alpha) mRNAs. Journal of virology. 1987;61(2):604–6. Epub 1987/02/01. 3027388; PubMed Central PMCID: PMC253989.

29. Lam Q, Smibert CA, Koop KE, Lavery C, Capone JP, Weinheimer SP, et al. Herpes simplex virus VP16 rescues viral mRNA from destruction by the virion host shutoff function. The EMBO journal. 1996;15(10):2575–81. Epub 1996/05/15. 8665865; PubMed Central PMCID: PMC450190.

30. Mbong EF, Woodley L, Dunkerley E, Schrimpf JE, Morrison LA, Duffy C. Deletion of the herpes simplex virus 1 UL49 gene results in mRNA and protein translation defects that are complemented by secondary mutations in UL41. Journal of virology. 2012;86(22):12351–61. doi: 10.1128/JVI.01975-12 22951838; PubMed Central PMCID: PMC3486455.

31. Shu M, Taddeo B, Zhang W, Roizman B. Selective degradation of mRNAs by the HSV host shutoff RNase is regulated by the UL47 tegument protein. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(18):E1669–75. doi: 10.1073/pnas.1305475110 23589852; PubMed Central PMCID: PMC3645526.

32. Smibert CA, Popova B, Xiao P, Capone JP, Smiley JR. Herpes simplex virus VP16 forms a complex with the virion host shutoff protein vhs. Journal of virology. 1994;68(4):2339–46. 8139019

33. Duerst RJ, Morrison LA. Herpes simplex virus 2 virion host shutoff protein interferes with type I interferon production and responsiveness. Virology. 2004;322(1):158–67. Epub 2004/04/06. doi: 10.1016/j.virol.2004.01.019 15063125.

34. Murphy JA, Duerst RJ, Smith TJ, Morrison LA. Herpes Simplex Virus Type 2 Virion Host Shutoff Protein Regulates Alpha/Beta Interferon but Not Adaptive Immune Responses during Primary Infection In Vivo. Journal of virology. 2003;77(17):9337–45. doi: 10.1128/JVI.77.17.9337-9345.2003 12915549

35. Pasieka TJ, Lu B, Crosby SD, Wylie KM, Morrison LA, Alexander DE, et al. Herpes Simplex Virus Virion Host Shutoff Attenuates Establishment of the Antiviral State. Journal of virology. 2008;82(11):5527–35. doi: 10.1128/JVI.02047-07 18367525

36. Dauber B, Pelletier J, Smiley JR. The herpes simplex virus 1 vhs protein enhances translation of viral true late mRNAs and virus production in a cell type-dependent manner. Journal of virology. 2011;85(11):5363–73. Epub 2011/03/25. doi: 10.1128/JVI.00115-11 21430045; PubMed Central PMCID: PMC3094992.

37. Finnen RL, Hay TJ, Dauber B, Smiley JR, Banfield BW. The herpes simplex virus 2 virion-associated ribonuclease vhs interferes with stress granule formation. Journal of virology. 2014;88(21):12727–39. doi: 10.1128/JVI.01554-14 25142597; PubMed Central PMCID: PMC4248931.

38. Dauber B, Poon D, dos Santos T, Duguay BA, Mehta N, Saffran HA, et al. The herpes simplex virus virion host shutoff protein enhances translation of viral true late mRNAs in the absence of protein kinase R. Journal of virology. 2016;90(13):6049–57. doi: 10.1128/JVI.03180-15 27099317; PubMed Central PMCID: PMC4907241.

39. Esclatine A, Taddeo B, Roizman B. Herpes Simplex Virus 1 Induces Cytoplasmic Accumulation of TIA-1/TIAR and both Synthesis and Cytoplasmic Accumulation of Tristetraprolin, Two Cellular Proteins That Bind and Destabilize AU-Rich RNAs. Journal of virology. 2004;78(16):8582–92. doi: 10.1128/JVI.78.16.8582-8592.2004 15280467

40. Dauber B, Saffran HA, Smiley JR. The herpes simplex virus 1 virion host shutoff protein enhances translation of viral late mRNAs by preventing mRNA overload. Journal of virology. 2014;88(17):9624–32. doi: 10.1128/JVI.01350-14 24920814; PubMed Central PMCID: PMC4136367.

41. Khaperskyy DA, Schmaling S, Larkins-Ford J, McCormick C, Gaglia MM. Selective Degradation of Host RNA Polymerase II Transcripts by Influenza A Virus PA-X Host Shutoff Protein. PLoS pathogens. 2016;12(2):e1005427. doi: 10.1371/journal.ppat.1005427 26849127; PubMed Central PMCID: PMC4744033.

42. Khaperskyy DA, Emara MM, Johnston BP, Anderson P, Hatchette TF, McCormick C. Influenza a virus host shutoff disables antiviral stress-induced translation arrest. PLoS pathogens. 2014;10(7):e1004217. doi: 10.1371/journal.ppat.1004217 25010204; PubMed Central PMCID: PMC4092144.

43. Burgess HM, Mohr I. Cellular 5'-3' mRNA exonuclease Xrn1 controls double-stranded RNA accumulation and anti-viral responses. Cell Host Microbe. 2015;17(3):332–44. doi: 10.1016/j.chom.2015.02.003 25766294; PubMed Central PMCID: PMC4826345.

44. Liu SW, Katsafanas GC, Liu R, Wyatt LS, Moss B. Poxvirus decapping enzymes enhance virulence by preventing the accumulation of dsRNA and the induction of innate antiviral responses. Cell Host Microbe. 2015;17(3):320–31. doi: 10.1016/j.chom.2015.02.002 25766293; PubMed Central PMCID: PMC4359750.

45. Reineke LC, Kedersha N, Langereis MA, van Kuppeveld FJ, Lloyd RE. Stress granules regulate double-stranded RNA-dependent protein kinase activation through a complex containing G3BP1 and Caprin1. mBio. 2015;6(2):e02486. Epub 2015/03/19. doi: 10.1128/mBio.02486-14 25784705; PubMed Central PMCID: PMC4453520.

46. Reineke LC, Lloyd RE. The stress granule protein G3BP1 recruits protein kinase R to promote multiple innate immune antiviral responses. Journal of virology. 2015;89(5):2575–89. Epub 2014/12/19. doi: 10.1128/JVI.02791-14 25520508; PubMed Central PMCID: PMC4325707.

47. Burgess HM, Mohr I. Defining the Role of Stress Granules in Innate Immune Suppression by the Herpes Simplex Virus 1 Endoribonuclease VHS. Journal of virology. 2018;92(15). Epub 2018/05/26. doi: 10.1128/JVI.00829-18 29793959; PubMed Central PMCID: PMC6052315.

48. Schonborn J, Oberstrass J, Breyel E, Tittgen J, Schumacher J, Lukacs N. Monoclonal antibodies to double-stranded RNA as probes of RNA structure in crude nucleic acid extracts. Nucleic acids research. 1991;19(11):2993–3000. doi: 10.1093/nar/19.11.2993 2057357; PubMed Central PMCID: PMC328262.

49. Ahmad S, Mu X, Yang F, Greenwald E, Park JW, Jacob E, et al. Breaching Self-Tolerance to Alu Duplex RNA Underlies MDA5-Mediated Inflammation. Cell. 2018;172(4):797–810 e13. doi: 10.1016/j.cell.2017.12.016 29395326; PubMed Central PMCID: PMC5807104.

50. Chung H, Calis JJA, Wu X, Sun T, Yu Y, Sarbanes SL, et al. Human ADAR1 Prevents Endogenous RNA from Triggering Translational Shutdown. Cell. 2018;172(4):811–24 e14. doi: 10.1016/j.cell.2017.12.038 29395325; PubMed Central PMCID: PMC5831367.

51. Dauber B, Pelletier J, Smiley JR. Correction for Dauber et al., “The herpes simplex virus 1 vhs protein enhances translation of viral true late mRNAs and virus production in a cell type-dependent manner.”. Journal of virology. 2019;93:e00985–16. doi: 10.1128/JVI.00985-19 31409732

52. Read GS, Karr BM, Knight K. Isolation of a herpes simplex virus type 1 mutant with a deletion in the virion host shutoff gene and identification of multiple forms of the vhs (UL41) polypeptide. Journal of virology. 1993;67(12):7149–60. 8230437

53. Jacquemont B, Roizman B. RNA synthesis in cells infected with herpes simplex virus. X. Properties of viral symmetric transcripts and of double-stranded RNA prepared from them. Journal of virology. 1975;15(4):707–13. 163916; PubMed Central PMCID: PMC354512.

54. Aloni Y. Extensive symmetrical transcription of Simian Virus 40 DNA in virus-yielding cells. Proceedings of the National Academy of Sciences of the United States of America. 1972;69(9):2404–9. Epub 1972/09/01. doi: 10.1073/pnas.69.9.2404 4341693; PubMed Central PMCID: PMC426950.

55. Colby C, Duesberg PH. Double-stranded RNA in vaccinia virus infected cells. Nature. 1969;222(5197):940–4. Epub 1969/06/07. doi: 10.1038/222940a0 5789322.

56. McGeoch DJ, Dalrymple MA, Davison AJ, Dolan A, Frame MC, McNab D, et al. The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. The Journal of general virology. 1988;69 (Pt 7):1531–74. Epub 1988/07/01. doi: 10.1099/0022-1317-69-7-1531 2839594.

57. Read GS, Sharp JA, Summers WC. In vitro and in vivo transcription initiation sites on the TK-encoding BamHI Q fragment of HSV-1 DNA. Virology. 1984;138(2):368–72. doi: 10.1016/0042-6822(84)90363-5 6093373.

58. Gompels U, Minson A. The properties and sequence of glycoprotein H of herpes simplex virus type 1. Virology. 1986;153(2):230–47. Epub 1986/09/01. doi: 10.1016/0042-6822(86)90026-7 3016991.

59. Kibler PK, Duncan J, Keith BD, Hupel T, Smiley JR. Regulation of herpes simplex virus true late gene expression: sequences downstream from the US11 TATA box inhibit expression from an unreplicated template. Journal of virology. 1991;65(12):6749–60. 1658372; PubMed Central PMCID: PMC250758.

60. Cook WJ, Coen DM. Temporal regulation of herpes simplex virus type 1 UL24 mRNA expression via differential polyadenylation. Virology. 1996;218(1):204–13. Epub 1996/04/01. doi: 10.1006/viro.1996.0180 8615023.

61. Tombacz D, Csabai Z, Szucs A, Balazs Z, Moldovan N, Sharon D, et al. Long-Read Isoform Sequencing Reveals a Hidden Complexity of the Transcriptional Landscape of Herpes Simplex Virus Type 1. Front Microbiol. 2017;8:1079. doi: 10.3389/fmicb.2017.01079 28676792; PubMed Central PMCID: PMC5476775.

62. White E, Schlackow M, Kamieniarz-Gdula K, Proudfoot NJ, Gullerova M. Human nuclear Dicer restricts the deleterious accumulation of endogenous double-stranded RNA. Nat Struct Mol Biol. 2014;21(6):552–9. Epub 2014/05/13. doi: 10.1038/nsmb.2827 24814348; PubMed Central PMCID: PMC4129937.

63. Gong C, Maquat LE. lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3' UTRs via Alu elements. Nature. 2011;470(7333):284–8. Epub 2011/02/11. doi: 10.1038/nature09701 21307942; PubMed Central PMCID: PMC3073508.

64. Gong C, Tang Y, Maquat LE. mRNA-mRNA duplexes that autoelicit Staufen1-mediated mRNA decay. Nat Struct Mol Biol. 2013;20(10):1214–20. Epub 2013/09/24. doi: 10.1038/nsmb.2664 24056942; PubMed Central PMCID: PMC3947523.

65. Loret S, Guay G, Lippe R. Comprehensive characterization of extracellular herpes simplex virus type 1 virions. Journal of virology. 2008;82(17):8605–18. Epub 2008/07/04. doi: 10.1128/JVI.00904-08 18596102; PubMed Central PMCID: PMC2519676.

66. Pheasant K, Moller-Levet CS, Jones J, Depledge D, Breuer J, Elliott G. Nuclear-cytoplasmic compartmentalization of the herpes simplex virus 1 infected cell transcriptome is co-ordinated by the viral endoribonuclease vhs and cofactors to facilitate the translation of late proteins. PLoS pathogens. 2018;14(11):e1007331. Epub 2018/11/27. doi: 10.1371/journal.ppat.1007331 30475899; PubMed Central PMCID: PMC6283614.

67. Liddicoat BJ, Chalk AM, Walkley CR. ADAR1, inosine and the immune sensing system: distinguishing self from non-self. Wiley interdisciplinary reviews RNA. 2016;7(2):157–72. Epub 2015/12/23. doi: 10.1002/wrna.1322 26692549.

68. Scadden AD. The RISC subunit Tudor-SN binds to hyper-edited double-stranded RNA and promotes its cleavage. Nat Struct Mol Biol. 2005;12(6):489–96. Epub 2005/05/17. doi: 10.1038/nsmb936 15895094.

69. Morita Y, Shibutani T, Nakanishi N, Nishikura K, Iwai S, Kuraoka I. Human endonuclease V is a ribonuclease specific for inosine-containing RNA. Nat Commun. 2013;4:2273. Epub 2013/08/06. doi: 10.1038/ncomms3273 23912718; PubMed Central PMCID: PMC3741642.

70. Park E, Maquat LE. Staufen-mediated mRNA decay. Wiley interdisciplinary reviews RNA. 2013;4(4):423–35. Epub 2013/05/18. doi: 10.1002/wrna.1168 23681777; PubMed Central PMCID: PMC3711692.

71. Elgadi MM, Hayes CE, Smiley JR. The herpes simplex virus vhs protein induces endoribonucleolytic cleavage of target RNAs in cell extracts. Journal of virology. 1999;73(9):7153–64. Epub 1999/08/10. 10438802; PubMed Central PMCID: PMC104239.

72. Karr BM, Read GS. The virion host shutoff function of herpes simplex virus degrades the 5' end of a target mRNA before the 3' end. Virology. 1999;264(1):195–204. Epub 1999/11/02. doi: 10.1006/viro.1999.9986 10544145.

73. Everly J, David N., Feng P, Mian IS, Read GS. mRNA Degradation by the Virion Host Shutoff (Vhs) Protein of Herpes Simplex Virus: Genetic and Biochemical Evidence that Vhs Is a Nuclease. Journal of virology. 2002;76(17):8560–71. doi: 10.1128/JVI.76.17.8560-8571.2002 12163576

74. Balakrishnan L, Bambara RA. Flap endonuclease 1. Annual review of biochemistry. 2013;82:119–38. Epub 2013/03/05. doi: 10.1146/annurev-biochem-072511-122603 23451868; PubMed Central PMCID: PMC3679248.

75. Cuellar WJ, Kreuze JF, Rajamaki ML, Cruzado KR, Untiveros M, Valkonen JP. Elimination of antiviral defense by viral RNase III. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(25):10354–8. Epub 2009/06/12. doi: 10.1073/pnas.0806042106 19515815; PubMed Central PMCID: PMC2694682.

76. Hastie KM, Kimberlin CR, Zandonatti MA, MacRae IJ, Saphire EO. Structure of the Lassa virus nucleoprotein reveals a dsRNA-specific 3' to 5' exonuclease activity essential for immune suppression. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(6):2396–401. Epub 2011/01/26. doi: 10.1073/pnas.1016404108 21262835; PubMed Central PMCID: PMC3038715.

77. Gierasch WW, Zimmerman DL, Ward SL, Vanheyningen TK, Romine JD, Leib DA. Construction and characterization of bacterial artificial chromosomes containing HSV-1 strains 17 and KOS. Journal of virological methods. 2006;135(2):197–206. Epub 2006/05/02. doi: 10.1016/j.jviromet.2006.03.014 16647145.

78. Tigges MA, Leng S, Johnson DC, Burke RL. Human herpes simplex virus (HSV)-specific CD8+ CTL clones recognize HSV-2-infected fibroblasts after treatment with IFN-gamma or when virion host shutoff functions are disabled. J Immunol. 1996;156(10):3901–10. Epub 1996/05/15. 8621929.

79. Tischer BK, Smith GA, Osterrieder N. En passant mutagenesis: a two step markerless red recombination system. Methods in molecular biology. 2010;634:421–30. Epub 2010/08/03. doi: 10.1007/978-1-60761-652-8_30 20677001.

80. Wang S, Zhao Y, Leiby M, Zhu J. A new positive/negative selection scheme for precise BAC recombineering. Molecular biotechnology. 2009;42(1):110–6. Epub 2009/01/23. doi: 10.1007/s12033-009-9142-3 19160076; PubMed Central PMCID: PMC2669495.

81. Child SJ, Hickson SE, Bayer A, Malouli D, Fruh K, Geballe AP. Antagonism of the Protein Kinase R Pathway in Human Cells by Rhesus Cytomegalovirus. Journal of virology. 2018;92(6). Epub 2017/12/22. doi: 10.1128/JVI.01793-17 29263260; PubMed Central PMCID: PMC5827409.

82. Arndt WD, White SD, Johnson BP, Huynh T, Liao J, Harrington H, et al. Monkeypox virus induces the synthesis of less dsRNA than vaccinia virus, and is more resistant to the anti-poxvirus drug, IBT, than vaccinia virus. Virology. 2016;497:125–35. Epub 2016/07/29. doi: 10.1016/j.virol.2016.07.016 27467578; PubMed Central PMCID: PMC5026613.

83. Frey TR, Lehmann MH, Ryan CM, Pizzorno MC, Sutter G, Hersperger AR. Ectromelia virus accumulates less double-stranded RNA compared to vaccinia virus in BS-C-1 cells. Virology. 2017;509:98–111. Epub 2017/06/20. doi: 10.1016/j.virol.2017.06.010 28628829; PubMed Central PMCID: PMC5541908.

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Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková, Ph.D.

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Multidisciplinární zkušenosti u pacientů s diabetem
Autoři: Prof. MUDr. Martin Haluzík, DrSc., prof. MUDr. Vojtěch Melenovský, CSc., prof. MUDr. Vladimír Tesař, DrSc.

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