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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Jul;86(1):113–119. doi: 10.1172/JCI114672

Productive infection of isolated human alveolar macrophages by respiratory syncytial virus.

J R Panuska 1, N M Cirino 1, F Midulla 1, J E Despot 1, E R McFadden Jr 1, Y T Huang 1
PMCID: PMC296697  PMID: 2365811

Abstract

Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract disease in children and individuals with cell-mediated immunodeficiencies. Airway epithelial cells may be infected with RSV, but it is unknown whether other cells within the lung permit viral replication. We studied whether human alveolar macrophages supported RSV replication in vitro. Alveolar macrophages exposed to RSV demonstrated expression of RSV fusion gene, which increased in a time-dependent manner and correlated with RSV protein expression. RSV-exposed alveolar macrophages produced and released infectious virus into supernatants for at least 25 d after infection. Viral production per alveolar macrophage declined from 0.053 plaque-forming units (pfu)/cell at 24 h after infection to 0.003 pfu/cell by 10 d after infection and then gradually increased. The capability of alveolar macrophages to support prolonged RSV replication may have a role in the pulmonary response to RSV infection.

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Selected References

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  1. Benveniste P., Derry H., Wu G. E., Paige C. J., Miller R. G. A sensitive dot blot procedure for detecting mRNA in lymphoid cells grown in liquid culture. J Immunol Methods. 1988 Mar 16;107(2):165–177. doi: 10.1016/0022-1759(88)90215-3. [DOI] [PubMed] [Google Scholar]
  2. Brain J. D. Lung macrophages: how many kinds are there? What do they do? Am Rev Respir Dis. 1988 Mar;137(3):507–509. doi: 10.1164/ajrccm/137.3.507. [DOI] [PubMed] [Google Scholar]
  3. Brautigam A. R., Dutko F. J., Olding L. B., Oldstone M. B. Pathogenesis of murine cytomegalovirus infection: the macrophage as a permissive cell for cytomegalovirus infection, replication and latency. J Gen Virol. 1979 Aug;44(2):349–359. doi: 10.1099/0022-1317-44-2-349. [DOI] [PubMed] [Google Scholar]
  4. Chandler D. B., Fulmer J. D. Prostaglandin synthesis and release by subpopulations of rat alveolar macrophages. J Immunol. 1987 Aug 1;139(3):893–898. [PubMed] [Google Scholar]
  5. Collins P. L., Huang Y. T., Wertz G. W. Nucleotide sequence of the gene encoding the fusion (F) glycoprotein of human respiratory syncytial virus. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7683–7687. doi: 10.1073/pnas.81.24.7683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Elias J. A., Schreiber A. D., Gustilo K., Chien P., Rossman M. D., Lammie P. J., Daniele R. P. Differential interleukin 1 elaboration by unfractionated and density fractionated human alveolar macrophages and blood monocytes: relationship to cell maturity. J Immunol. 1985 Nov;135(5):3198–3204. [PubMed] [Google Scholar]
  7. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  8. Fels A. O., Cohn Z. A. The alveolar macrophage. J Appl Physiol (1985) 1986 Feb;60(2):353–369. doi: 10.1152/jappl.1986.60.2.353. [DOI] [PubMed] [Google Scholar]
  9. Fishaut M., Schwartzman J. D., McIntosh K., Mostow S. R. Behavior of respiratory syncytial virus in piglet tracheal organ culture. J Infect Dis. 1978 Nov;138(5):644–649. doi: 10.1093/infdis/138.5.644. [DOI] [PubMed] [Google Scholar]
  10. Fishaut M., Tubergen D., McIntosh K. Cellular response to respiratory viruses with particular reference to children with disorders of cell-mediated immunity. J Pediatr. 1980 Feb;96(2):179–186. doi: 10.1016/s0022-3476(80)80799-2. [DOI] [PubMed] [Google Scholar]
  11. Gardner P. S., McQuillin J., Court S. D. Speculation on pathogenesis in death from respiratory syncytial virus infection. Br Med J. 1970 Feb 7;1(5692):327–330. doi: 10.1136/bmj.1.5692.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gimenez H. B., Keir H. M., Cash P. In vitro enhancement of respiratory syncytial virus infection of U937 cells by human sera. J Gen Virol. 1989 Jan;70(Pt 1):89–96. doi: 10.1099/0022-1317-70-1-89. [DOI] [PubMed] [Google Scholar]
  13. Isakov N., Feldman M., Segal S. Acute infection of mice with lactic dehydrogenase virus (LDV) impairs the antigen-presenting capacity of their macrophages. Cell Immunol. 1982 Jan 15;66(2):317–332. doi: 10.1016/0008-8749(82)90182-4. [DOI] [PubMed] [Google Scholar]
  14. Jakab G. J., Warr G. A. Immune-enhanced phagocytic dysfunction in pulmonary macrophages infected with parainfluenza 1 (Sendai) virus. Am Rev Respir Dis. 1981 Nov;124(5):575–581. doi: 10.1164/arrd.1981.124.5.575. [DOI] [PubMed] [Google Scholar]
  15. Johnson R. A., Prince G. A., Suffin S. C., Horswood R. L., Chanock R. M. Respiratory syncytial virus infection in cyclophosphamide-treated cotton rats. Infect Immun. 1982 Jul;37(1):369–373. doi: 10.1128/iai.37.1.369-373.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kemmerich B., Rossing T. H., Pennington J. E. Comparative oxidative microbicidal activity of human blood monocytes and alveolar macrophages and activation by recombinant gamma interferon. Am Rev Respir Dis. 1987 Aug;136(2):266–270. doi: 10.1164/ajrccm/136.2.266. [DOI] [PubMed] [Google Scholar]
  17. Krilov L. R., Hendry R. M., Godfrey E., McIntosh K. Respiratory virus infection of peripheral blood monocytes: correlation with ageing of cells and interferon production in vitro. J Gen Virol. 1987 Jun;68(Pt 6):1749–1753. doi: 10.1099/0022-1317-68-6-1749. [DOI] [PubMed] [Google Scholar]
  18. Kurlandsky L. E., French G., Webb P. M., Porter D. D. Fatal respiratory syncytial virus pneumonitis in a previously healthy child. Am Rev Respir Dis. 1988 Aug;138(2):468–472. doi: 10.1164/ajrccm/138.2.468. [DOI] [PubMed] [Google Scholar]
  19. Laude H., Charley B., Gelfi J. Replication of transmissible gastroenteritis coronavirus (TGEV) in swine alveolar macrophages. J Gen Virol. 1984 Feb;65(Pt 2):327–332. doi: 10.1099/0022-1317-65-2-327. [DOI] [PubMed] [Google Scholar]
  20. Linnavuori K., Hovi T. Restricted replication of herpes simplex virus in human monocyte cultures: role of interferon. Virology. 1983 Oct 15;130(1):1–9. doi: 10.1016/0042-6822(83)90112-5. [DOI] [PubMed] [Google Scholar]
  21. Martinet Y., Yamauchi K., Crystal R. G. Differential expression of the tumor necrosis factor/cachectin gene by blood and lung mononuclear phagocytes. Am Rev Respir Dis. 1988 Sep;138(3):659–665. doi: 10.1164/ajrccm/138.3.659. [DOI] [PubMed] [Google Scholar]
  22. Merz D. C., Scheid A., Choppin P. W. Importance of antibodies to the fusion glycoprotein of paramyxoviruses in the prevention of spread of infection. J Exp Med. 1980 Feb 1;151(2):275–288. doi: 10.1084/jem.151.2.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Midulla F., Huang Y. T., Gilbert I. A., Cirino N. M., McFadden E. R., Jr, Panuska J. R. Respiratory syncytial virus infection of human cord and adult blood monocytes and alveolar macrophages. Am Rev Respir Dis. 1989 Sep;140(3):771–777. doi: 10.1164/ajrccm/140.3.771. [DOI] [PubMed] [Google Scholar]
  24. Mills J. Effects of Sendai virus infection on function of cultured mouse alveolar macrophages. Am Rev Respir Dis. 1979 Dec;120(6):1239–1244. doi: 10.1164/arrd.1979.120.6.1239. [DOI] [PubMed] [Google Scholar]
  25. Mogensen S. C. Role of macrophages in natural resistance to virus infections. Microbiol Rev. 1979 Mar;43(1):1–26. doi: 10.1128/mr.43.1.1-26.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Morahan P. S., Connor J. R., Leary K. R. Viruses and the versatile macrophage. Br Med Bull. 1985 Jan;41(1):15–21. doi: 10.1093/oxfordjournals.bmb.a072017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Oldstone M. B. Viral persistence. Cell. 1989 Feb 24;56(4):517–520. doi: 10.1016/0092-8674(89)90573-4. [DOI] [PubMed] [Google Scholar]
  28. Olmsted R. A., Elango N., Prince G. A., Murphy B. R., Johnson P. R., Moss B., Chanock R. M., Collins P. L. Expression of the F glycoprotein of respiratory syncytial virus by a recombinant vaccinia virus: comparison of the individual contributions of the F and G glycoproteins to host immunity. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7462–7466. doi: 10.1073/pnas.83.19.7462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. P'ringle C. R., Shirodaria P. V., Cash P., Chiswell D. J., Malloy P. Initiation and maintenance of persistent infection by respiratory syncytial virus. J Virol. 1978 Oct;28(1):199–211. doi: 10.1128/jvi.28.1.199-211.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Panuska J. R., Fukui K., Parker C. W. Secreted proteins of human monocytes. Analysis by two-dimensional gel electrophoresis and effect of lipopolysaccharide. Biochem J. 1988 Jan 15;249(2):501–511. doi: 10.1042/bj2490501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Parks D. R., Bryan V. M., Oi V. T., Herzenberg L. A. Antigen-specific identification and cloning of hybridomas with a fluorescence-activated cell sorter. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1962–1966. doi: 10.1073/pnas.76.4.1962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Peluso R., Haase A., Stowring L., Edwards M., Ventura P. A Trojan Horse mechanism for the spread of visna virus in monocytes. Virology. 1985 Nov;147(1):231–236. doi: 10.1016/0042-6822(85)90246-6. [DOI] [PubMed] [Google Scholar]
  33. Rich E. A., Panuska J. R., Wallis R. S., Wolf C. B., Leonard M. L., Ellner J. J. Dyscoordinate expression of tumor necrosis factor-alpha by human blood monocytes and alveolar macrophages. Am Rev Respir Dis. 1989 Apr;139(4):1010–1016. doi: 10.1164/ajrccm/139.4.1010. [DOI] [PubMed] [Google Scholar]
  34. Rich E. A., Tweardy D. J., Fujiwara H., Ellner J. J. Spectrum of immunoregulatory functions and properties of human alveolar macrophages. Am Rev Respir Dis. 1987 Aug;136(2):258–265. doi: 10.1164/ajrccm/136.2.258. [DOI] [PubMed] [Google Scholar]
  35. Roberts N. J., Jr Different effects of influenza virus, respiratory syncytial virus, and Sendai virus on human lymphocytes and macrophages. Infect Immun. 1982 Mar;35(3):1142–1146. doi: 10.1128/iai.35.3.1142-1146.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Roberts N. J., Jr, Prill A. H., Mann T. N. Interleukin 1 and interleukin 1 inhibitor production by human macrophages exposed to influenza virus or respiratory syncytial virus. Respiratory syncytial virus is a potent inducer of inhibitor activity. J Exp Med. 1986 Mar 1;163(3):511–519. doi: 10.1084/jem.163.3.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Roy S., Fitz-Gibbon L., Poulin L., Wainberg M. A. Infection of human monocytes/macrophages by HIV-1: effect on secretion of IL-1 activity. Immunology. 1988 Jun;64(2):233–239. [PMC free article] [PubMed] [Google Scholar]
  38. Stott E. J., Taylor G. Respiratory syncytial virus. Brief review. Arch Virol. 1985;84(1-2):1–52. doi: 10.1007/BF01310552. [DOI] [PubMed] [Google Scholar]
  39. Streissle G. Persistent viral infections as models for research in virus chemotherapy. Adv Virus Res. 1981;26:37–64. doi: 10.1016/S0065-3527(08)60420-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Toth T., Hesse R. A. Replication of five bovine respiratory viruses in cultured bovine alveolar macrophages. Arch Virol. 1983;75(3):219–224. doi: 10.1007/BF01315276. [DOI] [PubMed] [Google Scholar]
  41. Treuhaft M. W., Beem M. O. Defective interfering particles of respiratory syncytial virus. Infect Immun. 1982 Aug;37(2):439–444. doi: 10.1128/iai.37.2.439-444.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Trigo E., Liggitt H. D., Evermann J. F., Breeze R. G., Huston L. Y., Silflow R. Effect of in vitro inoculation of bovine respiratory syncytial virus on bovine pulmonary alveolar macrophage function. Am J Vet Res. 1985 May;46(5):1098–1103. [PubMed] [Google Scholar]
  43. Walsh E. E., Brandriss M. W., Schlesinger J. J. Purification and characterization of the respiratory syncytial virus fusion protein. J Gen Virol. 1985 Mar;66(Pt 3):409–415. doi: 10.1099/0022-1317-66-3-409. [DOI] [PubMed] [Google Scholar]
  44. Welliver R. C. Viral infections and obstructive airway disease in early life. Pediatr Clin North Am. 1983 Oct;30(5):819–828. doi: 10.1016/s0031-3955(16)34467-4. [DOI] [PubMed] [Google Scholar]
  45. Wewers M. D., Rennard S. I., Hance A. J., Bitterman P. B., Crystal R. G. Normal human alveolar macrophages obtained by bronchoalveolar lavage have a limited capacity to release interleukin-1. J Clin Invest. 1984 Dec;74(6):2208–2218. doi: 10.1172/JCI111647. [DOI] [PMC free article] [PubMed] [Google Scholar]

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