RSV-encoded NS2 promotes epithelial cell shedding and distal airway obstruction

Journal of Clinical Investigation

Volumn 124, Issue 5, 2014, Pages 2219-2233

  Liesman, Rachael M ^a   Buchholz, Ursula J ^b   Luongo, Cindy L ^b   Yang, Lijuan ^b   Proia, Alan D ^c   DeVincenzo, John P ^d   Collins, Peter L ^b   Pickles, Raymond J ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^c DUKE UNIVERSITY MEDICAL CENTER   (United States)

^d LE BONHEUR CHILDREN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

NONSTRUCTURAL PROTEIN 2;

ACUTE DISEASE; AIRWAY OBSTRUCTION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOACCUMULATION; CELLULAR, SUBCELLULAR AND MOLECULAR BIOLOGICAL PHENOMENA AND FUNCTIONS; CONTROLLED STUDY; EPITHELIUM CELL; EPITHELIUM CELL SHEDDING; FEMALE; HAMSTER MODEL; HEP 2 CELL LINE; HISTOPATHOLOGY; HUMAN; HUMAN CELL; IN VITRO STUDY; INOCULATION; NONHUMAN; PRIORITY JOURNAL; RESPIRATORY EPITHELIUM; RESPIRATORY SYNCYTIAL PNEUMOVIRUS; RESPIRATORY SYNCYTIAL VIRUS INFECTION; RESPIRATORY TRACT MUCOSA; VIRAL CLEARANCE; VIROGENESIS; VIRUS REPLICATION;

ADOLESCENT; ADULT; AIRWAY OBSTRUCTION; ANIMALS; CELL LINE; CHILD; CHILD, PRESCHOOL; CRICETINAE; EPITHELIAL CELLS; FEMALE; HUMANS; MALE; MESOCRICETUS; RESPIRATORY MUCOSA; RESPIRATORY SYNCYTIAL VIRUS INFECTIONS; RESPIRATORY SYNCYTIAL VIRUSES; VIRAL NONSTRUCTURAL PROTEINS;

EID: 84899716199     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI72948     Document Type: Article

References (70)

1. Glezen WP, Taber LH, Frank AL, Kasel JA. Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child. 1986;140(6):543-546.
2. Hall CB, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med. 2009; 360(6):588-598.
3. Nair H, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010;375(9725):1545-1555.
4. Krilov LR. Safety issues related to the administration of ribavirin. Pediatr Infect Dis J. 2002;21(5):479-481.
5. Davison C, Ventre KM, Luchetti M, Randolph AG. Efficacy of interventions for bronchiolitis in critically ill infants: a systematic review and meta-analysis. Pediatr Crit Care Med. 2004;5(5):482-489.
6. Garrison MM, Christakis DA, Harvey E, Cummings P, Davis RL. Systemic corticosteroids in infant bronchiolitis: a meta-analysis. Pediatrics. 2000; 105(4):E44.
7. van Woensel JB, Vyas H, STAR Trial Group. Dexamethasone in children mechanically ventilated for lower respiratory tract infection caused by respiratory syncytial virus: a randomized controlled trial. Crit Care Med. 2011;39(7):1779-1783.
8. Committee on Infectious Diseases. From the American Academy of Pediatrics: Policy statements - modified recommendations for use of palivizumab for prevention of respiratory syncytial virus infections. Pediatrics. 2009;124(6):1694-1701.
9. Null D Jr, et al. Safety and immunogenicity of palivizumab (Synagis) administered for two seasons. Pediatr Infect Dis J. 2005;24(11):1021-1023.
10. Johnson JE, Gonzales RA, Olson SJ, Wright PF, Graham BS. The histopathology of fatal untreated human respiratory syncytial virus infection. Mod Pathol. 2007;20(1):108-119.
11. Shedden WI, Emery JL. Immunofluorescent evidence of respiratory syncytial virus infection in cases of giant cell bronchiolitis in children. J Pathol Bacteriol. 1965;89:343-347.
12. Welliver TP, Reed JL, Welliver RC Sr. Respiratory syncytial virus and influenza virus infections: observations from tissues of fatal infant cases. Pediatr Infect Dis J. 2008;27(10 suppl):S92-S96.
13. Villenave R, et al. In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo. Proc Natl Acad Sci U S A. 2012;109(13):5040-5045.
14. Zhang L, Peeples ME, Boucher RC, Collins PL, Pickles RJ. Respiratory syncytial virus infection of human airway epithelial cells is polarized, specific to ciliated cells, and without obvious cytopathology. J Virol. 2002;76(11):5654-5666.
15. Sims AC, Baric RS, Yount B, Burkett SE, Collins PL, Pickles RJ. Severe acute respiratory syndrome coronavirus infection of human ciliated airway epithelia: role of ciliated cells in viral spread in the conducting airways of the lungs. J Virol. 2005; 79(24):15511-15524.
16. Thompson CI, Barclay WS, Zambon MC, Pickles RJ. Infection of human airway epithelium by human and avian strains of influenza a virus. J Virol. 2006;80(16):8060-8068.
17. Zhang L, Collins PL, Lamb RA, Pickles RJ. Comparison of differing cytopathic effects in human airway epithelium of parainfluenza virus 5 (W3A), parainfluenza virus type 3, and respiratory syncytial virus. Virology. 2011;421(1):67-77.
18. Scull MA, et al. Avian Influenza virus glycoproteins restrict virus replication and spread through human airway epithelium at temperatures of the proximal airways. PLoS Pathog. 2009;5(5):e1000424.
19. Spann KM, Tran KC, Collins PL. Effects of nonstructural proteins NS1 and NS2 of human respiratory syncytial virus on interferon regulatory factor 3, NF-B, and proinflammatory cytokines. J Virol. 2005;79(9):5353-5362.
20. Liu C, Sharp E, Collins J. Studies on the pathogenesis of parainfluenza type 3 virus infection in hamsters. Arch Gesamte Virusforsch. 1968;24(3):203-219.
21. García CG, et al. Risk factors in children hospitalized with RSV bronchiolitis versus non-RSV bronchiolitis. Pediatrics. 2010;126(6):e1453-e1460.
22. Hervas D, Reina J, Yanez A, del Valle JM, Figuerola J, Hervas JA. Epidemiology of hospitalization for acute bronchiolitis in children: differences between RSV and non-RSV bronchiolitis. Eur J Clin Microbiol Infect Dis. 2012;31(8):1975-1981.
23. Bourgeois FT, Valim C, McAdam AJ, Mandl KD. Relative impact of influenza and respiratory syncytial virus in young children. Pediatrics. 2009; 124(6):e1072-e1080.
24. McNamara PS, Ritson P, Selby A, Hart CA, Smyth RL. Bronchoalveolar lavage cellularity in infants with severe respiratory syncytial virus bronchiolitis. Arch Dis Child. 2003;88(10):922-926.
25. Blanken MO, et al. Respiratory syncytial virus and recurrent wheeze in healthy preterm infants. N Engl J Med. 2013;368(19):1791-1799.
26. Sigurs N, et al. Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life. Thorax. 2010;65(12):1045-1052.
27. Bossert B, Conzelmann KK. Respiratory syncytial virus (RSV) nonstructural (NS) proteins as host range determinants: a chimeric bovine RSV with NS genes from human RSV is attenuated in interferon-competent bovine cells. J Virol. 2002; 76(9):4287-4293.
28. Welliver TP, et al. Severe human lower respiratory tract illness caused by respiratory syncytial virus and influenza virus is characterized by the absence of pulmonary cytotoxic lymphocyte responses. J Infect Dis. 2007;195(8):1126-1136.
29. Hislop AA, Haworth SG. Airway size and structure in the normal fetal and infant lung and the effect of premature delivery and artificial ventilation. Am Rev Respir Dis. 1989;140(6):1717-1726.
30. Boers JE, Ambergen AW, Thunnissen FB. Number and proliferation of clara cells in normal human airway epithelium. Am J Respir Crit Care Med. 1999; 159(5 pt 1):1585-1591.
31. Christensen TG, Breuer R, Hornstra LJ, Lucey EC, Snider GL. The ultrastructure of hamster bronchial epithelium. Exp Lung Res. 1987;13(3):253-277.
32. Bryson DG, Platten MF, McConnell S, McNulty MS. Ultrastructural features of lesions in bronchiolar epithelium in induced respiratory syncytial virus pneumonia of calves. Vet Pathol. 1991; 28(4):293-299.
33. Derscheid RJ, Ackermann MR. Perinatal lamb model of respiratory syncytial virus (RSV) infection. Viruses. 2012;4(10):2359-2378.
34. Olivier A, Gallup J, de Macedo MM, Varga SM, Ackermann M. Human respiratory syncytial virus A2 strain replicates and induces innate immune responses by respiratory epithelia of neonatal lambs. Int J Exp Pathol. 2009;90(4):431-438.
35. Papin JF, et al. Infant baboons infected with respiratory syncytial virus develop clinical and pathological changes that parallel those of human infants. Am J Physiol Lung Cell Mol Physiol. 2013; 304(8):L530-L539.
36. Smith CM, et al. Ciliary dyskinesia is an early feature of respiratory syncytial virus infection. Eur Respir J. 2014;43(2):485-496.
37. Aherne W, Bird T, Court SD, Gardner PS, McQuillin J. Pathological changes in virus infections of the lower respiratory tract in children. J Clin Pathol. 1970;23(1):7-18.
38. Simpson W, Hacking PM, Court SD, Gardner PS. The radiological findings in respiratory syncytial virus infection in children. II. The correlation of radiological categories with clinical and virological findings. Pediatr Radiol. 1974;2(3):155-160.
39. DeVincenzo JP, et al. Viral load drives disease in humans experimentally infected with respiratory syncytial virus. Am J Respir Crit Care Med. 2010; 182(10):1305-1314.
40. Hall CB, Douglas RG Jr, Geiman JM. Respiratory syncytial virus infections in infants: quantitation and duration of shedding. J Pediatr. 1976;89(1):11-15.
41. Spann KM, Tran KC, Chi B, Rabin RL, Collins PL. Suppression of the induction of alpha, beta, and lambda interferons by the NS1 and NS2 proteins of human respiratory syncytial virus in human epithelial cells and macrophages [corrected]. J Virol. 2004; 78(8):4363-4369.
42. Whitehead SS, et al. Recombinant respiratory syncytial virus bearing a deletion of either the NS2 or SH gene is attenuated in chimpanzees. J Virol. 1999; 73(4):3438-3442.
43. Wright PF, et al. The interferon antagonist NS2 protein of respiratory syncytial virus is an important virulence determinant for humans. J Infect Dis. 2006;193(4):573-581.
44. Teng MN, et al. Recombinant respiratory syncytial virus that does not express the NS1 or M2-2 protein is highly attenuated and immunogenic in chimpanzees. J Virol. 2000;74(19):9317-9321.
45. Hastie ML, et al. The human respiratory syncytial virus nonstructural protein 1 regulates type I and type II interferon pathways. Mol Cell Proteomics. 2012;11(5):108-127.
46. Ling Z, Tran KC, Teng MN. Human respiratory syncytial virus nonstructural protein NS2 antagonizes the activation of beta interferon transcription by interacting with RIG-I. J Virol. 2009;83(8):3734-3742.
47. Ramaswamy M, Shi L, Varga SM, Barik S, Behlke MA, Look DC. Respiratory syncytial virus nonstructural protein 2 specifically inhibits type I interferon signal transduction. Virology. 2006; 344(2):328-339.
48. Swedan S, Musiyenko A, Barik S. Respiratory syncytial virus nonstructural proteins decrease levels of multiple members of the cellular interferon pathways. J Virol. 2009;83(19):9682-9693.
49. Bitko V, et al. Nonstructural proteins of respiratory syncytial virus suppress premature apoptosis by an NF-B-dependent, interferon-independent mechanism and facilitate virus growth. J Virol. 2007; 81(4):1786-1795.
50. Bitko V, Oldenburg A, Garmon NE, Barik S. Profilin is required for viral morphogenesis, syncytium formation, and cell-specific stress fiber induction by respiratory syncytial virus. BMC Microbiol. 2003;3:9.
51. Burke E, Dupuy L, Wall C, Barik S. Role of cellular actin in the gene expression and morphogenesis of human respiratory syncytial virus. Virology. 1998; 252(1):137-148.
52. Garcia-Barreno B, Jorcano JL, Aukenbauer T, Lopez-Galindez C, Melero JA. Participation of cytoskeletal intermediate filaments in the infectious cycle of human respiratory syncytial virus (RSV). Virus Res. 1988;9(4):307-321.
53. Kallewaard NL, Bowen AL, Crowe JE Jr. Cooperativity of actin and microtubule elements during replication of respiratory syncytial virus. Virology. 2005; 331(1):73-81.
54. Luongo C, Winter CC, Collins PL, Buchholz UJ. Respiratory syncytial virus modified by deletions of the NS2 gene and amino acid S1313 of the L polymerase protein is a temperature-sensitive, live-attenuated vaccine candidate that is phenotypically stable at physiological temperature. J Virol. 2013; 87(4):1985-1996.
55. Fulcher ML, Gabriel S, Burns KA, Yankaskas JR, Randell SH. Well-differentiated human airway epithelial cell cultures. Methods Mol Med. 2005; 107:183-206.
56. Biacchesi S, Skiadopoulos MH, Tran KC, Murphy BR, Collins PL, Buchholz UJ. Recovery of human metapneumovirus from cDNA: optimization of growth in vitro and expression of additional genes. Virology. 2004;321(2):247-259.
57. He B, Paterson RG, Ward CD, Lamb RA. Recovery of infectious SV5 from cloned DNA and expression of a foreign gene. Virology. 1997;237(2):249-260.
58. Iseni F, Garcin D, Nishio M, Kedersha N, Anderson P, Kolakofsky D. Sendai virus trailer RNA binds TIAR, a cellular protein involved in virus-induced apoptosis. EMBO J. 2002;21(19):5141-5150.
59. Collins PL, Hill MG, Camargo E, Grosfeld H, Chanock RM, Murphy BR. Production of infectious human respiratory syncytial virus from cloned cDNA confirms an essential role for the transcription elongation factor from the 5'proximal open reading frame of the M2 mRNA in gene expression and provides a capability for vaccine development. Proc Natl Acad Sci U S A. 1995;92(25):11563-11567.
60. Spann KM, Collins PL, Teng MN. Genetic recombination during coinfection of two mutants of human respiratory syncytial virus. J Virol. 2003; 77(20):11201-11211.
61. Teng MN, Collins PL. Altered growth characteristics of recombinant respiratory syncytial viruses which do not produce NS2 protein. J Virol. 1999;73(1):466-473.
62. Young DF, et al. Virus replication in engineered human cells that do not respond to interferons. J Virol. 2003;77(3):2174-2181.
63. Durbin AP, Hall SL, Siew JW, Whitehead SS, Collins PL, Murphy BR. Recovery of infectious human parainfluenza virus type 3 from cDNA. Virology. 1997;235(2):323-332.
64. Zhang L, et al. Infection of ciliated cells by human parainfluenza virus type 3 in an in vitro model of human airway epithelium. J Virol. 2005; 79(2):1113-1124.
65. Zhang L, et al. CFTR delivery to 25% of surface epithelial cells restores normal rates of mucus transport to human cystic fibrosis airway epithelium. PLoS Biol. 2009;7(7):e1000155.
66. Zhang L, et al. Fetoprotein gene delivery to the nasal epithelium of nonhuman primates by human parainfluenza viral vectors. Hum Gene Ther. 2010; 21(12):1657-1664.
67. Newman JT, et al. Sequence analysis of the Washington/ 1964 strain of human parainfluenza virus type 1 (HPIV1) and recovery and characterization of wild-type recombinant HPIV1 produced by reverse genetics. Virus Genes. 2002;24(1):77-92.
68. Kesimer M, Ehre C, Burns KA, Davis CW, Sheehan JK, Pickles RJ. Molecular organization of the mucins and glycocalyx underlying mucus transport over mucosal surfaces of the airways. Mucosal Immunol. 2013;6(2):379-392.
69. Bukreyev A, et al. Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against Ebola virus challenge. Virology. 2009;383(2):348-361.
70. Sisson JH, Stoner JA, Ammons BA, Wyatt TA. All-digital image capture and whole-field analysis of ciliary beat frequency. J Microsc. 2003;211(pt 2):103-111.