Effect of Loss-of-function of the Herpes Simplex Virus-1 microRNA H6-5p on Virus Replication
Tóm tắt
To date, 29 distinct microRNAs (miRNAs) have been reported to be expressed during herpes simplex virus infections. Sequence analysis of mature herpes simplex virus-1 (HSV-1) miRNAs revealed five sets of miRNAs that are complementary to each other: miR-H6-5p/H1-3p, miR-H6-3p/H1-5p, H2-5p/H14-3p, miR-H2-3p/H14-5p, and miR-H7/H27. However, the roles of individual miRNAs and consequences of this complementarity remain unclear. Here, we focus on two of these complementary miRNAs, miR-H6-5p and miR-H1-3p, using loss-of-function experiments in vitro and in a mouse model of infection using an miRNA sponge approach, including tandem multiplex artificial miRNA-binding sequences that do not match perfectly to the target miRNA inserted downstream of a green fluorescent protein reporter gene. Infection with recombinant virus expressing the miR-H6-5p sponge reduced viral protein levels and virus yield. Decreased accumulation of viral proteins was also observed at early stages of infection in the presence of both an miR-H6-5p inhibitor and plasmid-expressed miR-H1-3p. Moreover, establishment of latency and reactivation did not differ between the recombinant virus expressing the miR-H6-5p sponge and wild-type HSV-1. Taken together, these data suggest that miR-H6-5p has an as-yet-unidentified role in the early stages of viral infection, and its complement miR-H1-3p suppresses this role in later stages of infection. This report extends understanding of the roles of miRNAs in infection by herpes simplex viruses, supporting a model of infection in which the production of virus and its virulent effects are tightly controlled to maximize persistence in the host and population.
Tài liệu tham khảo
Ackermann M, Braun DK, Pereira L, Roizman B (1984) Characterization of herpes simplex virus 1 alpha proteins 0, 4, and 27 with monoclonal antibodies. J Virol 52:108–118
Aranda AM, Epstein AL (2015) Herpes simplex virus type 1 latency and reactivation: an update. Med Sci (Paris) 31:506–514
Bloom DC (2016) Alphaherpesvirus latency: a dynamic state of transcription and reactivation. Adv Virus Res 94:53–80
Carter CJ (2011) Alzheimer's disease plaques and tangles: cemeteries of a pyrrhic victory of the immune defence network against herpes simplex infection at the expense of complement and inflammation-mediated neuronal destruction. Neurochem Int 58:301–320
Cui C, Griffiths A, Li G, Silva LM, Kramer MF, Gaasterland T (2006) Prediction and identification of herpes simplex virus 1-encoded microRNAs. J Virol 80:5499–5508
Cui Y, Yu H, Zheng X, Peng R, Wang Q, Zhou Y, Wang R, Wang J, Qu B, Shen N, Guo Q, Liu X, Wang C (2017) SENP7 potentiates cGAS activation by relieving SUMO-mediated inhibition of cytosolic DNA sensing. PLoS Pathog 13:e1006156
Du T, Zhou G, Roizman B (2011) HSV-1 gene expression from reactivated ganglia is disordered and concurrent with suppression of latency-associated transcript and miRNAs. Proc Natl Acad Sci USA 108:18820–18824
Du T, Han Z, Zhou G, Roizman B (2015) Patterns of accumulation of miRNAs encoded by herpes simplex virus during productive infection, latency, and on reactivation. Proc Natl Acad Sci USA 112:E49–55
Ebert MS, Sharp PA (2010) MicroRNA sponges: progress and possibilities. RNA 16:2043–2050
Ejercito PM, Kieff ED, Roizman B (1968) Characterization of herpes simplex virus strains differing in their effects on social behaviour of infected cells. J Gen Virol 2:357–364
Enk J, Levi A, Weisblum Y, Yamin R, Charpak-Amikam Y, Wolf DG (2016) HSV1 MicroRNA modulation of GPI anchoring and downstream immune evasion. Cell Rep 17:949–956
Flores O, Nakayama S, Whisnant AW, Javanbakht H, Cullen BR, Bloom DC (2013) Mutational inactivation of herpes simplex virus 1 microRNAs identifies viral mRNA targets and reveals phenotypic effects in culture. J Virol 87:6589–6603
Gregory D, Hargett D, Holmes D, Money E, Bachenheimer SL (2004) Efficient replication by herpes simplex virus type 1 involves activation of the IkappaB kinase-IkappaB-p65 pathway. J Virol 78:13582–13590
Gu H, Roizman B (2007) Herpes simplex virus-infected cell protein 0 blocks the silencing of viral DNA by dissociating histone deacetylases from the CoREST-REST complex. Proc Natl Acad Sci USA 104:17134–17139
Han Z, Liu X, Chen X, Zhou X, Du T, Roizman B (2016) miR-H28 and miR-H29 expressed late in productive infection are exported and restrict HSV-1 replication and spread in recipient cells. Proc Natl Acad Sci USA 113:E894–901
Horwich MD, Zamore PD (2008) Design and delivery of antisense oligonucleotides to block microRNA function in cultured drosophila and human cells. Nat Protoc 3:1537–1549
Jiang X, Brown D, Osorio N, Hsiang C, BenMohamed L, Wechsler SL (2016) Increased neurovirulence and reactivation of the herpes simplex virus type 1 latency-associated transcript (LAT)-negative mutant dLAT2903 with a disrupted LAT miR-H2. J Neurovirol 22:38–49
Jurak I, Kramer MF, Mellor JC, van Lint AL, Roth FP, Knipe DM (2010) Numerous conserved and divergent microRNAs expressed by herpes simplex viruses 1 and 2. J Virol 84:4659–4672
Jurak I, Hackenberg M, Kim JY, Pesola JM, Everett RD, Preston CM (2014) Expression of herpes simplex virus 1 microRNAs in cell culture models of quiescent and latent infection. J Virol 88:2337–2339
Kim H, Iizasa H, Kanehiro Y, Fekadu S, Yoshiyama H (2017) Herpesviral microRNAs in cellular metabolism and immune responses. Front Microbiol 8:1318
Kluiver J, Slezak-Prochazka I, Smigielska-Czepiel K, Halsema N, Kroesen BJ, van den Berg A (2012) Generation of miRNA sponge constructs. Methods 58:113–117
Kramer MF, Jurak I, Pesola JM, Boissel S, Knipe DM, Coen DM (2011) Herpes simplex virus 1 microRNAs expressed abundantly during latent infection are not essential for latency in mouse trigeminal ganglia. Virology 417:239–247
Kurata JS, Lin RJ (2018) MicroRNA-focused CRISPR-Cas9 library screen reveals fitness-associated miRNAs. RNA 24:966–981
Liu Z, Sall A, Yang D (2008) MicroRNA: an emerging therapeutic target and intervention tool. Int J Mol Sci 9:978–999
Mallon S, Wakim BT, Roizman B (2012) Use of biotinylated plasmid DNA as a surrogate for HSV DNA to identify proteins that repress or activate viral gene expression. Proc Natl Acad Sci USA 109:E3549–3557
Martinez-Torres FJ, Völcker D, Dörner N, Lenhard T, Nielsen S, Haas J, Kiening K, Meyding-Lamadé U (2007) Aquaporin 4 regulation during acute and long-term experimental Herpes simplex virus encephalitis. J Neurovirol 13:38–46
McKnight JL, Kristie TM, Roizman B (1987) Binding of the virion protein mediating alpha gene induction in herpes simplex virus 1-infected cells to its cis site requires cellular proteins. Proc Natl Acad Sci USA 84:7061–7065
Munson DJ, Burch AD (2012) A novel miRNA produced during lytic HSV-1 infection is important for efficient replication in tissue culture. Arch Virol 157:1677–1688
Roizman B, Whitley RJ (2013) An inquiry into the molecular basis of HSV latency and reactivation. Annu Rev Microbiol 67:355–374
Roller RJ, Roizman B (1992) The herpes simplex virus 1 RNA binding protein US11 is a virion component and associates with ribosomal 60S subunits. J Virol 66:3624–3632
Sun L, Li Q (2012) The miRNAs of herpes simplex virus (HSV). Virol Sin 27:333–338
Tay FC, Lim JK, Zhu H, Hin LC, Wang S (2015) Using artificial microRNA sponges to achieve microRNA loss-of-function in cancer cells. Adv Drug Deliv Rev 81:117–127
Umbach JL, Kramer MF, Jurak I, Karnowski HW, Coen DM, Cullen BR (2008) MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs. Nature 454:780–783
Umbach JL, Nagel MA, Cohrs RJ, Gilden DH, Cullen BR (2009) Analysis of human alphaherpesvirus microRNA expression in latently infected human trigeminal ganglia. J Virol 83:10677–10683
Wang S, Mott KR, Cilluffo M, Kilpatrick CL, Murakami S, Ljubimov AV, Kousoulas KG, Awasthi S, Luscher B, Ghiasi H (2018) The absence of DHHC3 affects primary and latent herpes simplex virus 1 infection. J Virol 92:e01599–17
Wu W, Guo Z, Zhang X, Guo L, Liu L, Liao Y (2013) A microRNA encoded by HSV-1 inhibits a cellular transcriptional repressor of viral immediate early and early genes. Sci China Life Sci 56:373–383
Yu X, He S (2016) The interplay between human herpes simplex virus infection and the apoptosis and necroptosis cell death pathways. Virol J 13:77
Zhao H, Zhang C, Hou G, Song J (2015) MicroRNA-H4-5p encoded by HSV-1 latency-associated transcript promotes cell proliferation, invasion and cell cycle progression via p16-mediated PI3 K-Akt signaling pathway in SHSY5Y cells. Int J Clin Exp Med 8:7526–7534