Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Apr;85(4):1324–1327. doi: 10.1172/JCI114571

Measles virus-substance P receptor interactions. Possible novel mechanism of viral fusion.

G Harrowe 1, M Mitsuhashi 1, D G Payan 1
PMCID: PMC296570  PMID: 1690758

Abstract

Measles virus (MV) encodes the fusion protein (F) that mediates cell fusion and intercellular spread of the virus, and is homologous to the carboxy terminus of the neuropeptide substance P (SP). In addition, the oligopeptide Z-D-Phe-L-Phe-Gly, also homologous to F and SP, inhibits MV fusion with target cells. These observations raise the question of whether MV uses the SP receptor (SPR) during a specific phase of its infectious cycle. In this report, we examine the structural and functional consequences of this interaction and show, using cross-linking studies, that MV and SP specifically bind to a 52-58-kD protein, previously reported to comprise the SPR on human IM-9 lymphoblasts. Moreover, bound MV and SP are shown to reciprocally displace each other from these cells. In addition, we demonstrate that anti-SP antisera inhibits the cell-to-cell spread of MV, and that SP blocks MV fusion with target cells. These results indicate the presence of MV-SPR interactions during viral fusion, and suggest possible novel mechanisms for viral entry into cells.

Full text

PDF
1324

Images in this article

1325Image
on p.1325

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blumenthal R., Bali-Puri A., Walter A., Covell D., Eidelman O. pH-dependent fusion of vesicular stomatitis virus with Vero cells. Measurement by dequenching of octadecyl rhodamine fluorescence. J Biol Chem. 1987 Oct 5;262(28):13614–13619. [PubMed] [Google Scholar]
  2. Co M. S., Gaulton G. N., Tominaga A., Homcy C. J., Fields B. N., Greene M. I. Structural similarities between the mammalian beta-adrenergic and reovirus type 3 receptors. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5315–5318. doi: 10.1073/pnas.82.16.5315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Eppstein D. A., Marsh Y. V., Schreiber A. B., Newman S. R., Todaro G. J., Nestor J. J., Jr Epidermal growth factor receptor occupancy inhibits vaccinia virus infection. Nature. 1985 Dec 19;318(6047):663–665. doi: 10.1038/318663a0. [DOI] [PubMed] [Google Scholar]
  4. Fingeroth J. D., Weis J. J., Tedder T. F., Strominger J. L., Biro P. A., Fearon D. T. Epstein-Barr virus receptor of human B lymphocytes is the C3d receptor CR2. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4510–4514. doi: 10.1073/pnas.81.14.4510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Krah D. L., Choppin P. W. Mice immunized with measles virus develop antibodies to a cell surface receptor for binding virus. J Virol. 1988 May;62(5):1565–1572. doi: 10.1128/jvi.62.5.1565-1572.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  7. Lentz T. L., Burrage T. G., Smith A. L., Crick J., Tignor G. H. Is the acetylcholine receptor a rabies virus receptor? Science. 1982 Jan 8;215(4529):182–184. doi: 10.1126/science.7053569. [DOI] [PubMed] [Google Scholar]
  8. McDougal J. S., Mawle A., Cort S. P., Nicholson J. K., Cross G. D., Scheppler-Campbell J. A., Hicks D., Sligh J. Cellular tropism of the human retrovirus HTLV-III/LAV. I. Role of T cell activation and expression of the T4 antigen. J Immunol. 1985 Nov;135(5):3151–3162. [PubMed] [Google Scholar]
  9. McGillis J. P., Organist M. L., Payan D. G. Immunoaffinity purification of membrane protein constituents of the IM-9 lymphoblast receptor for substance P. Anal Biochem. 1987 Aug 1;164(2):502–513. doi: 10.1016/0003-2697(87)90525-2. [DOI] [PubMed] [Google Scholar]
  10. McGrath M., Witte O., Pincus T., Weissman I. L. Retrovirus purification: method that conserves envelope glycoprotein and maximizes infectivity. J Virol. 1978 Mar;25(3):923–927. doi: 10.1128/jvi.25.3.923-927.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mountcastle W. E., Choppin P. W. A comparison of the polypeptides of four measles virus strains. Virology. 1977 May 15;78(2):463–474. doi: 10.1016/0042-6822(77)90123-4. [DOI] [PubMed] [Google Scholar]
  12. Organist M. L., Harvey J. P., McGillis J. P., Payan D. G. Processing of the human IM-9 lymphoblast substance P receptor. Biosynthetic and degradation studies using a monoclonal anti-receptor antibody. Biochem Biophys Res Commun. 1988 Feb 29;151(1):535–541. doi: 10.1016/0006-291x(88)90627-4. [DOI] [PubMed] [Google Scholar]
  13. Payan D. G., McGillis J. P., Organist M. L. Binding characteristics and affinity labeling of protein constituents of the human IM-9 lymphoblast receptor for substance P. J Biol Chem. 1986 Oct 25;261(30):14321–14329. [PubMed] [Google Scholar]
  14. Richardson C. D., Choppin P. W. Oligopeptides that specifically inhibit membrane fusion by paramyxoviruses: studies on the site of action. Virology. 1983 Dec;131(2):518–532. doi: 10.1016/0042-6822(83)90517-2. [DOI] [PubMed] [Google Scholar]
  15. Richardson C. D., Scheid A., Choppin P. W. Specific inhibition of paramyxovirus and myxovirus replication by oligopeptides with amino acid sequences similar to those at the N-termini of the F1 or HA2 viral polypeptides. Virology. 1980 Aug;105(1):205–222. doi: 10.1016/0042-6822(80)90168-3. [DOI] [PubMed] [Google Scholar]
  16. Saban R., Dick E. C., Fishleder R. I., Buckner C. K. Enhancement by parainfluenza 3 infection of contractile responses to substance P and capsaicin in airway smooth muscle from the guinea pig. Am Rev Respir Dis. 1987 Sep;136(3):586–591. doi: 10.1164/ajrccm/136.3.586. [DOI] [PubMed] [Google Scholar]
  17. Scheid A., Choppin P. W. Two disulfide-linked polypeptide chains constitute the active F protein of paramyxoviruses. Virology. 1977 Jul 1;80(1):54–66. doi: 10.1016/0042-6822(77)90380-4. [DOI] [PubMed] [Google Scholar]
  18. Schroeder C. Substance P, a neuropeptide, inhibits measles virus replication in cell culture. Acta Virol. 1986 Sep;30(5):432–435. [PubMed] [Google Scholar]
  19. Varsanyi T. M., Utter G., Norrby E. Purification, morphology and antigenic characterization of measles virus envelope components. J Gen Virol. 1984 Feb;65(Pt 2):355–366. doi: 10.1099/0022-1317-65-2-355. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES