The endonucleolytic RNA cleavage function of nsp1 of middle east respiratory syndrome coronavirus promotes the production of infectious virus particles in specific human cell lines

Journal of Virology

Volumn 92, Issue 21, 2018, Pages

  Nakagawa, Keisuke ^a   Narayanan, Krishna ^a   Wada, Masami ^a   Popov, Vsevolod L ^a   Cajimat, Maria ^a   Baric, Ralph S ^c   Makino, Shinji ^a,b  

^a University of Texas Medical Branch School of Medicine   (United States)

^b UNIVERSITY OF TEXAS MEDICAL BRANCH   (United States)

^c University of North Carolina at Chapel Hill   (United States)

Author keywords

MERS coronavirus; Nsp1; Virus assembly budding

Indexed keywords

BETA INTERFERON; NSP1 PROTEIN; RNA; UNCLASSIFIED DRUG; VIRAL PROTEIN; VIRUS RECEPTOR; GAMMA INTERFERON; IFNG PROTEIN, HUMAN; MESSENGER RNA;

293 DERIVED CELL; ARTICLE; BIOLOGICAL FUNCTIONS; CELLS; CONTROLLED STUDY; GAPDH GENE; GENE; GENE REPRESSION; HELA CELL LINE; HUH-7 CELL LINE; HUMAN; HUMAN CELL; IFN BETA GENE; IFN LAMBDA GENE; MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; RNA CLEAVAGE; RNA DEGRADATION; VERO CELL LINE; VIRUS ASSEMBLY; VIRUS PARTICLE; VIRUS RELEASE; VIRUS REPLICATION; VIRUS TITRATION; ANIMAL; BIOSYNTHESIS; CELL LINE; CHLOROCEBUS AETHIOPS; CORONAVIRUS INFECTION; GENE EXPRESSION; GENETICS; HEK293 CELL LINE; METABOLISM; PATHOLOGY; PHYSIOLOGY; RNA STABILITY;

ANIMALS; CELL LINE; CERCOPITHECUS AETHIOPS; CORONAVIRUS INFECTIONS; GENE EXPRESSION; HEK293 CELLS; HELA CELLS; HUMANS; INTERFERON-BETA; INTERFERON-GAMMA; MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS; RNA CLEAVAGE; RNA STABILITY; RNA, MESSENGER; VERO CELLS; VIRAL NONSTRUCTURAL PROTEINS; VIRUS ASSEMBLY;

EID: 85054898355     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.01157-18     Document Type: Article

References (85)

1. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. 2012. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 367:1814-1820. https://doi.org/10 .1056/NEJMoa1211721.
2. Hui DS, Azhar EI, Kim YJ, Memish ZA, Oh MD, Zumla A. 2018. Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission. Lancet Infect Dis 18: e217-e227. https://doi.org/10.1016/S1473-3099(18)30127-0.
3. Lee HJ, Shieh CK, Gorbalenya AE, Koonin EV, La Monica N, Tuler J, Bagdzhadzhyan A, Lai MM. 1991. The complete sequence (22 kilobases) of murine coronavirus gene 1 encoding the putative proteases and RNA polymerase. Virology 180:567-582. https://doi.org/10.1016/ 0042-6822(91)90071-I.
4. Lomniczi B. 1977. Biological properties of avian coronavirus RNA. J Gen Virol 36:531-533. https://doi.org/10.1099/0022-1317-36-3-531.
5. Lomniczi B, Kennedy I. 1977. Genome of infectious bronchitis virus. J Virol 24:99-107.
6. Raj VS, Mou H, Smits SL, Dekkers DH, Muller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL. 2013. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 495:251-254. https://doi.org/10.1038/nature12005.
7. Burkard C, Verheije MH, Wicht O, van Kasteren SI, van Kuppeveld FJ, Haagmans BL, Pelkmans L, Rottier PJ, Bosch BJ, de Haan CA. 2014. Coronavirus cell entry occurs through the endo-/lysosomal pathway in a proteolysis-dependent manner. PLoS Pathog 10:e1004502. https://doi .org/10.1371/journal.ppat.1004502.
8. Snijder EJ, Decroly E, Ziebuhr J. 2016. The nonstructural proteins directing coronavirus RNA synthesis and processing. Adv Virus Res 96:59-126. https://doi.org/10.1016/bs.aivir.2016.08.008.
9. Hurst-Hess KR, Kuo L, Masters PS. 2015. Dissection of amino-terminal functional domains of murine coronavirus nonstructural protein 3. J Virol 89:6033-6047. https://doi.org/10.1128/JVI.00197-15.
10. Graham RL, Sims AC, Brockway SM, Baric RS, Denison MR. 2005. The nsp2 replicase proteins of murine hepatitis virus and severe acute respiratory syndrome coronavirus are dispensable for viral replication. J Virol 79: 13399-13411. https://doi.org/10.1128/JVI.79.21.13399-13411.2005.
11. Neuman BW, Chamberlain P, Bowden F, Joseph J. 2014. Atlas of coronavirus replicase structure. Virus Res 194:49-66. https://doi.org/ 10.1016/j.virusres.2013.12.004.
12. Masters PS. 2006. The molecular biology of coronaviruses. Adv Virus Res 66:193-292. https://doi.org/10.1016/S0065-3527(06)66005-3.
13. Sawicki SG, Sawicki DL, Siddell SG. 2007. A contemporary view of coronavirus transcription. J Virol 81:20-29. https://doi.org/10.1128/JVI .01358-06.
14. Lai MM, Baric RS, Brayton PR, Stohlman SA. 1984. Characterization of leader RNA sequences on the virion and mRNAs of mouse hepatitis virus, a cytoplasmic RNA virus. Proc Natl Acad Sci U S A 81:3626-3630. https://doi.org/10.1073/pnas.81.12.3626.
15. Lai MM, Patton CD, Baric RS, Stohlman SA. 1983. Presence of leader sequences in the mRNA of mouse hepatitis virus. J Virol 46:1027-1033.
16. Lai MM, Patton CD, Stohlman SA. 1982. Replication of mouse hepatitis virus: negative-stranded RNA and replicative form RNA are of genome length. J Virol 44:487-492.
17. Liu DX, Fung TS, Chong KK, Shukla A, Hilgenfeld R. 2014. Accessory proteins of SARS-CoV and other coronaviruses. Antiviral Res 109:97-109. https://doi.org/10.1016/j.antiviral.2014.06.013.
18. Narayanan K, Huang C, Makino S. 2008. SARS coronavirus accessory proteins. Virus Res 133:113-121. https://doi.org/10.1016/j.virusres.2007 .10.009.
19. Menachery VD, Mitchell HD, Cockrell AS, Gralinski LE, Yount BL, Jr, Graham RL, McAnarney ET, Douglas MG, Scobey T, Beall A, Dinnon K, III, Kocher JF, Hale AE, Stratton KG, Waters KM, Baric RS. 2017. MERS-CoV accessory ORFs play key role for infection and pathogenesis. mBio 8:e00665-17. https://doi.org/10.1128/mBio.00665-17.
20. Stertz S, Reichelt M, Spiegel M, Kuri T, Martinez-Sobrido L, Garcia-Sastre A, Weber F, Kochs G. 2007. The intracellular sites of early replication and budding of SARS-coronavirus. Virology 361:304-315. https://doi.org/10 .1016/j.virol.2006.11.027.
21. Tooze J, Tooze S, Warren G. 1984. Replication of coronavirus MHV-A59 in sac-cells: determination of the first site of budding of progeny virions. Eur J Cell Biol 33:281-293.
22. Klumperman J, Locker JK, Meijer A, Horzinek MC, Geuze HJ, Rottier PJ. 1994. Coronavirus M proteins accumulate in the Golgi complex beyond the site of virion budding. J Virol 68:6523-6534.
23. Vennema H, Godeke GJ, Rossen JW, Voorhout WF, Horzinek MC, Opstelten DJ, Rottier PJ. 1996. Nucleocapsid-independent assembly of coronavirus-like particles by coexpression of viral envelope protein genes. EMBO J 15:2020-2028.
24. de Haan CA, Smeets M, Vernooij F, Vennema H, Rottier PJ. 1999. Mapping of the coronavirus membrane protein domains involved in interaction with the spike protein. J Virol 73:7441-7452.
25. Escors D, Ortego J, Laude H, Enjuanes L. 2001. The membrane M protein carboxy terminus binds to transmissible gastroenteritis coronavirus core and contributes to core stability. J Virol 75:1312-1324. https://doi.org/ 10.1128/JVI.75.3.1312-1324.2001.
26. Escors D, Camafeita E, Ortego J, Laude H, Enjuanes L. 2001. Organization of two transmissible gastroenteritis coronavirus membrane protein topologies within the virion and core. J Virol 75:12228-12240. https://doi .org/10.1128/JVI.75.24.12228-12240.2001.
27. Kuo L, Masters PS. 2002. Genetic evidence for a structural interaction between the carboxy termini of the membrane and nucleocapsid proteins of mouse hepatitis virus. J Virol 76:4987-4999. https://doi.org/10 .1128/JVI.76.10.4987-4999.2002.
28. Nguyen VP, Hogue BG. 1997. Protein interactions during coronavirus assembly. J Virol 71:9278-9284.
29. Opstelten DJ, Raamsman MJ, Wolfs K, Horzinek MC, Rottier PJ. 1995. Envelope glycoprotein interactions in coronavirus assembly. J Cell Biol 131:339-349. https://doi.org/10.1083/jcb.131.2.339.
30. Corse E, Machamer CE. 2000. Infectious bronchitis virus E protein is targeted to the Golgi complex and directs release of virus-like particles. J Virol 74:4319-4326. https://doi.org/10.1128/JVI.74.9.4319-4326.2000.
31. Bos EC, Luytjes W, van der Meulen HV, Koerten HK, Spaan WJ. 1996. The production of recombinant infectious DI-particles of a murine coronavirus in the absence of helper virus. Virology 218:52-60. https://doi.org/ 10.1006/viro.1996.0165.
32. Fischer F, Stegen CF, Masters PS, Samsonoff WA. 1998. Analysis of constructed E gene mutants of mouse hepatitis virus confirms a pivotal role for E protein in coronavirus assembly. J Virol 72:7885-7894.
33. DeDiego ML, Alvarez E, Almazan F, Rejas MT, Lamirande E, Roberts A, Shieh WJ, Zaki SR, Subbarao K, Enjuanes L. 2007. A severe acute respiratory syndrome coronavirus that lacks the E gene is attenuated in vitro and in vivo. J Virol 81:1701-1713. https://doi.org/10.1128/JVI.01467-06.
34. Narayanan K, Ramirez SI, Lokugamage KG, Makino S. 2015. Coronavirus nonstructural protein 1: common and distinct functions in the regulation of host and viral gene expression. Virus Res 202:89-100. https://doi.org/ 10.1016/j.virusres.2014.11.019.
35. Connor RF, Roper RL. 2007. Unique SARS-CoV protein nsp1: bioinformatics, biochemistry, and potential effects on virulence. Trends Microbiol 15:51-53. https://doi.org/10.1016/j.tim.2006.12.005.
36. Jansson AM. 2013. Structure of alphacoronavirus transmissible gastroenteritis virus nsp1 has implications for coronavirus nsp1 function and evolution. J Virol 87:2949-2955. https://doi.org/10.1128/JVI.03163-12.
37. Snijder EJ, Bredenbeek PJ, Dobbe JC, Thiel V, Ziebuhr J, Poon LL, Guan Y, Rozanov M, Spaan WJ, Gorbalenya AE. 2003. Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage. J Mol Biol 331:991-1004. https:// doi.org/10.1016/S0022-2836(03)00865-9.
38. Thiel V, Ivanov KA, Putics A, Hertzig T, Schelle B, Bayer S, Weissbrich B, Snijder EJ, Rabenau H, Doerr HW, Gorbalenya AE, Ziebuhr J. 2003. Mechanisms and enzymes involved in SARS coronavirus genome expression. J Gen Virol 84:2305-2315. https://doi.org/10.1099/vir.0.19424-0.
39. Tohya Y, Narayanan K, Kamitani W, Huang C, Lokugamage K, Makino S. 2009. Suppression of host gene expression by nsp1 proteins of group 2 bat coronaviruses. J Virol 83:5282-5288. https://doi.org/10 .1128/JVI.02485-08.
40. Kamitani W, Huang C, Narayanan K, Lokugamage KG, Makino S. 2009. A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein. Nat Struct Mol Biol 16:1134-1140. https://doi.org/ 10.1038/nsmb.1680.
41. Kamitani W, Narayanan K, Huang C, Lokugamage K, Ikegami T, Ito N, Kubo H, Makino S. 2006. Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression by promoting host mRNA degradation. Proc Natl Acad Sci U S A 103:12885-12890. https://doi.org/ 10.1073/pnas.0603144103.
42. Huang C, Lokugamage KG, Rozovics JM, Narayanan K, Semler BL, Makino S. 2011. Alphacoronavirus transmissible gastroenteritis virus nsp1 protein suppresses protein translation in mammalian cells and in cell-free HeLa cell extracts but not in rabbit reticulocyte lysate. J Virol 85: 638-643. https://doi.org/10.1128/JVI.01806-10.
43. Lokugamage KG, Narayanan K, Nakagawa K, Terasaki K, Ramirez SI, Tseng CT, Makino S. 2015. Middle East respiratory syndrome coronavirus nsp1 inhibits host gene expression by selectively targeting mRNAs transcribed in the nucleus while sparing mRNAs of cytoplasmic origin. J Virol 89:10970-10981. https://doi.org/10.1128/JVI.01352-15.
44. Gaglia MM, Covarrubias S, Wong W, Glaunsinger BA. 2012. A common strategy for host RNA degradation by divergent viruses. J Virol 86: 9527-9530. https://doi.org/10.1128/JVI.01230-12.
45. Huang C, Lokugamage KG, Rozovics JM, Narayanan K, Semler BL, Makino S. 2011. SARS coronavirus nsp1 protein induces templatedependent endonucleolytic cleavage of mRNAs: viral mRNAs are resistant to nsp1-induced RNA cleavage. PLoS Pathog 7:e1002433. https://doi.org/10.1371/journal.ppat.1002433.
46. Narayanan K, Huang C, Lokugamage K, Kamitani W, Ikegami T, Tseng CT, Makino S. 2008. Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells. J Virol 82:4471-4479. https://doi.org/10.1128/JVI.02472-07.
47. Wathelet MG, Orr M, Frieman MB, Baric RS. 2007. Severe acute respiratory syndrome coronavirus evades antiviral signaling: role of nsp1 and rational design of an attenuated strain. J Virol 81:11620-11633. https:// doi.org/10.1128/JVI.00702-07.
48. Zhang Q, Ke H, Blikslager A, Fujita T, Yoo D. 2018. Type III interferon restriction by porcine epidemic diarrhea virus and the role of viral protein nsp1 in IRF1 signaling. J Virol 92:e01677-17. https://doi.org/10 .1128/JVI.01677-17.
49. Zust R, Cervantes-Barragan L, Kuri T, Blakqori G, Weber F, Ludewig B, Thiel V. 2007. Coronavirus nonstructural protein 1 is a major pathogenicity factor: implications for the rational design of coronavirus vaccines. PLoS Pathog 3:e109. https://doi.org/10.1371/journal.ppat.0030109.
50. Zhang R, Li Y, Cowley TJ, Steinbrenner AD, Phillips JM, Yount BL, Baric RS, Weiss SR. 2015. The nsp1, nsp13, and M proteins contribute to the hepatotropism of murine coronavirus JHM.WU. J Virol 89:3598-3609. https://doi.org/10.1128/JVI.03535-14.
51. Jimenez-Guardeno JM, Regla-Nava JA, Nieto-Torres JL, DeDiego ML, Castano-Rodriguez C, Fernandez-Delgado R, Perlman S, Enjuanes L. 2015. Identification of the mechanisms causing reversion to virulence in an attenuated SARS-CoV for the design of a genetically stable vaccine. PLoS Pathog 11:e1005215. https://doi.org/10.1371/journal.ppat.1005215.
52. Tanaka T, Kamitani W, DeDiego ML, Enjuanes L, Matsuura Y. 2012. Severe acute respiratory syndrome coronavirus nsp1 facilitates efficient propagation in cells through a specific translational shutoff of host mRNA. J Virol 86:11128-11137. https://doi.org/10.1128/JVI.01700-12.
53. Terada Y, Kawachi K, Matsuura Y, Kamitani W. 2017. MERS coronavirus nsp1 participates in an efficient propagation through a specific interaction with viral RNA. Virology 511:95-105. https://doi.org/10.1016/j.virol .2017.08.026.
54. Scobey T, Yount BL, Sims AC, Donaldson EF, Agnihothram SS, Menachery VD, Graham RL, Swanstrom J, Bove PF, Kim JD, Grego S, Randell SH, Baric RS. 2013. Reverse genetics with a full-length infectious cDNA of the Middle East respiratory syndrome coronavirus. Proc Natl Acad Sci U S A 110:16157-16162. https://doi.org/10.1073/pnas.1311542110.
55. Tseng CT, Tseng J, Perrone L, Worthy M, Popov V, Peters CJ. 2005. Apical entry and release of severe acute respiratory syndrome-associated coronavirus in polarized Calu-3 lung epithelial cells. J Virol 79:9470-9479. https://doi.org/10.1128/JVI.79.15.9470-9479.2005.
56. Nakabayashi H, Taketa K, Miyano K, Yamane T, Sato J. 1982. Growth of human hepatoma cells lines with differentiated functions in chemically defined medium. Cancer Res 42:3858-3863.
57. Mou H, Raj VS, van Kuppeveld FJ, Rottier PJ, Haagmans BL, Bosch BJ. 2013. The receptor binding domain of the new Middle East respiratory syndrome coronavirus maps to a 231-residue region in the spike protein that efficiently elicits neutralizing antibodies. J Virol 87:9379-9383. https://doi.org/10.1128/JVI.01277-13.
58. Hume AJ, Ames J, Rennick LJ, Duprex WP, Marzi A, Tonkiss J, Muhlberger E. 2016. Inactivation of RNA viruses by gamma irradiation: a study on mitigating factors. Viruses 8:E204. https://doi.org/10.3390/v8070204.
59. Lomax ME, Folkes LK, O'Neill P. 2013. Biological consequences of radiation-induced DNA damage: relevance to radiotherapy. Clin Oncol 25:578-585. https://doi.org/10.1016/j.clon.2013.06.007.
60. Ohshima H, Iida Y, Matsuda A, Kuwabara M. 1996. Damage induced by hydroxyl radicals generated in the hydration layer of gamma-irradiated frozen aqueous solution of DNA. J Radiat Res 37:199-207. https://doi .org/10.1269/jrr.37.199.
61. Summers WC, Szybalski W. 1967. Gamma-irradiation of deoxyribonucleic acid in dilute solutions. II. Molecular mechanisms responsible for inactivation of phage, its transfecting DNA, and of bacterial transforming activity. J Mol Biol 26:227-235.
62. Ward RL. 1980. Mechanisms of poliovirus inactivation by the direct and indirect effects of ionizing radiation. Radiat Res 83:330-344. https://doi .org/10.2307/3575284.
63. Ruch TR, Machamer CE. 2012. The coronavirus E protein: assembly and beyond. Viruses 4:363-382. https://doi.org/10.3390/v4030363.
64. Baudoux P, Carrat C, Besnardeau L, Charley B, Laude H. 1998. Coronavirus pseudoparticles formed with recombinant M and E proteins induce alpha interferon synthesis by leukocytes. J Virol 72:8636-8643.
65. Wang SM, Huang KJ, Wang CT. 2014. BST2/CD317 counteracts human coronavirus 229E productive infection by tethering virions at the cell surface. Virology 449:287-296. https://doi.org/10.1016/j.virol.2013.11 .030.
66. Neil SJ, Zang T, Bieniasz PD. 2008. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451:425-430. https://doi.org/10 .1038/nature06553.
67. Kaletsky RL, Francica JR, Agrawal-Gamse C, Bates P. 2009. Tetherinmediated restriction of filovirus budding is antagonized by the Ebola glycoprotein. Proc Natl Acad Sci U S A 106:2886-2891. https://doi.org/ 10.1073/pnas.0811014106.
68. Mansouri M, Viswanathan K, Douglas JL, Hines J, Gustin J, Moses AV, Fruh K. 2009. Molecular mechanism of BST2/tetherin downregulation by K5/MIR2 of Kaposi's sarcoma-associated herpesvirus. J Virol 83: 9672-9681. https://doi.org/10.1128/JVI.00597-09.
69. Jouvenet N, Neil SJ, Zhadina M, Zang T, Kratovac Z, Lee Y, McNatt M, Hatziioannou T, Bieniasz PD. 2009. Broad-spectrum inhibition of retroviral and filoviral particle release by tetherin. J Virol 83:1837-1844. https://doi.org/10.1128/JVI.02211-08.
70. Hayashi T, MacDonald LA, Takimoto T. 2015. Influenza A virus protein PA-X contributes to viral growth and suppression of the host antiviral and immune responses. J Virol 89:6442-6452. https://doi.org/10.1128/ JVI.00319-15.
71. Xu G, Zhang X, Liu Q, Bing G, Hu Z, Sun H, Xiong X, Jiang M, He Q, Wang Y, Pu J, Guo X, Yang H, Liu J, Sun Y. 2017. PA-X protein contributes to virulence of triple-reassortant H1N2 influenza virus by suppressing early immune responses in swine. Virology 508:45-53. https://doi.org/10 .1016/j.virol.2017.05.002.
72. Lee J, Yu H, Li Y, Ma J, Lang Y, Duff M, Henningson J, Liu Q, Li Y, Nagy A, Bawa B, Li Z, Tong G, Richt JA, Ma W. 2017. Impacts of different expressions of PA-X protein on 2009 pandemic H1N1 virus replication, pathogenicity and host immune responses. Virology 504:25-35. https:// doi.org/10.1016/j.virol.2017.01.015.
73. Tigges MA, Leng S, Johnson DC, Burke RL. 1996. 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 156:3901-3910.
74. Pasieka TJ, Lu B, Crosby SD, Wylie KM, Morrison LA, Alexander DE, Menachery VD, Leib DA. 2008. Herpes simplex virus virion host shutoff attenuates establishment of the antiviral state. J Virol 82:5527-5535. https://doi.org/10.1128/JVI.02047-07.
75. Murphy JA, Duerst RJ, Smith TJ, Morrison LA. 2003. Herpes simplex virus type 2 virion host shutoff protein regulates alpha/beta interferon but not adaptive immune responses during primary infection in vivo. J Virol 77:9337-9345. https://doi.org/10.1128/JVI.77.17.9337-9345.2003.
76. Finnen RL, Zhu M, Li J, Romo D, Banfield BW. 2016. Herpes simplex virus 2 virion host shutoff endoribonuclease activity is required to disrupt stress granule formation. J Virol 90:7943-7955. https://doi.org/10.1128/ JVI.00947-16.
77. Dauber B, Pelletier J, Smiley JR. 2011. The herpes simplex virus 1 Vhs protein enhances translation of viral true late mRNAs and virus production in a cell type-dependent manner. J Virol 85:5363-5373. https://doi .org/10.1128/JVI.00115-11.
78. Finnen RL, Hay TJ, Dauber B, Smiley JR, Banfield BW. 2014. The herpes simplex virus 2 virion-associated ribonuclease Vhs interferes with stress granule formation. J Virol 88:12727-12739. https://doi.org/10 .1128/JVI.01554-14.
79. Dauber B, Poon D, Dos Santos T, Duguay BA, Mehta N, Saffran HA, Smiley JR. 2016. 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. J Virol 90:6049-6057. https:// doi.org/10.1128/JVI.03180-15.
80. Agrawal AS, Garron T, Tao X, Peng BH, Wakamiya M, Chan TS, Couch RB, Tseng CT. 2015. Generation of a transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease. J Virol 89: 3659-3670. https://doi.org/10.1128/JVI.03427-14.
81. Falzarano D, de Wit E, Rasmussen AL, Feldmann F, Okumura A, Scott DP, Brining D, Bushmaker T, Martellaro C, Baseler L, Benecke AG, Katze MG, Munster VJ, Feldmann H. 2013. Treatment with interferon-2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat Med 19:1313-1317. https://doi.org/10.1038/nm.3362.
82. Falzarano D, de Wit E, Feldmann F, Rasmussen AL, Okumura A, Peng X, Thomas MJ, van Doremalen N, Haddock E, Nagy L, LaCasse R, Liu T, Zhu J, McLellan JS, Scott DP, Katze MG, Feldmann H, Munster VJ. 2014. Infection with MERS-CoV causes lethal pneumonia in the common marmoset. PLoS Pathog 10:e1004250. https://doi.org/10.1371/ journal.ppat.1004250.
83. Cockrell AS, Yount BL, Scobey T, Jensen K, Douglas M, Beall A, Tang XC, Marasco WA, Heise MT, Baric RS. 2016. A mouse model for MERS coronavirus-induced acute respiratory distress syndrome. Nat Microbiol 2:16226. https://doi.org/10.1038/nmicrobiol.2016.226.
84. Abernathy E, Glaunsinger B. 2015. Emerging roles for RNA degradation in viral replication and antiviral defense. Virology 479-480:600-608. https://doi.org/10.1016/j.virol.2015.02.007.
85. Read GS. 2013. Virus-encoded endonucleases: expected and novel functions. Wiley Interdiscip Rev RNA 4:693-708. https://doi.org/10.1002/wcs .1258.