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. 1996 Jan;70(1):612–616. doi: 10.1128/jvi.70.1.612-616.1996

The v-erbB oncogene confers enhanced cellular susceptibility to reovirus infection.

J E Strong 1, P W Lee 1
PMCID: PMC189854  PMID: 8523580

Abstract

We have previously demonstrated that two mouse cell lines that are poorly infectible by reovirus become highly susceptible upon transfection with the gene encoding the epidermal growth factor receptor (EGFR) (J. E. Strong, D. Tang, and P. W. K. Lee, Virology 197:405-411, 1993). This enhancement of infection efficiency requires a functional EGFR, since such an enhancement is not observed in cells expressing a mutated (kinase-inactive) EGFR. The additional finding that reovirus is capable of directly binding to the N-terminal ectodomain of the EGFR (D. Tang, J. E. Strong, and P. W. K. Lee, Virology 197:412-414, 1993) has led us to question whether this interaction is required for the activation of a signalling cascade that somehow augments the ensuing infection process. In the present study, we address this question, using cells transfected with the v-erbB oncogene, which encodes a protein structurally related to the EGFR but lacking a large portion of the N-terminal ligand-binding domain. The v-erbB protein also possesses ligand-independent, constitutive tyrosine kinase activity. Control NIH 3T3 cells, which are poorly infectible by reovirus (serotype 3, strain Dearing), and NIH 3T3 cells transfected with the v-erbB oncogene (THC-11) were assayed for their susceptibilities to reovirus infection. Infectivity was determined by immunofluorescent detection of viral proteins, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of radiolabeled cells, and plaque titration. All three assays demonstrated a drastically higher degree of susceptibility to infection in the THC-11 cell line. This enhanced susceptibility was found to be abrogated by treatment of the cells with genistein, an inhibitor of tyrosine protein kinases, but only partially by treatment with daidzein, an inactive analog of genistein. We propose that the mechanism of enhancement of infection efficiency conferred by EGFR and v-erbB is through the opportunistic utilization by the virus of an already activated signal transduction pathway.

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Selected References

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  1. Akiyama T., Ishida J., Nakagawa S., Ogawara H., Watanabe S., Itoh N., Shibuya M., Fukami Y. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem. 1987 Apr 25;262(12):5592–5595. [PubMed] [Google Scholar]
  2. Beug H., Hayman M. J., Raines M. B., Kung H. J., Vennström B. Rous-associated virus 1-induced erythroleukemic cells exhibit a weakly transformed phenotype in vitro and release c-erbB-containing retroviruses unable to transform fibroblasts. J Virol. 1986 Mar;57(3):1127–1138. doi: 10.1128/jvi.57.3.1127-1138.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Choi A. H., Lee P. W. Does the beta-adrenergic receptor function as a reovirus receptor? Virology. 1988 Mar;163(1):191–197. doi: 10.1016/0042-6822(88)90246-2. [DOI] [PubMed] [Google Scholar]
  4. Choi A. H., Paul R. W., Lee P. W. Reovirus binds to multiple plasma membrane proteins of mouse L fibroblasts. Virology. 1990 Sep;178(1):316–320. doi: 10.1016/0042-6822(90)90412-k. [DOI] [PubMed] [Google Scholar]
  5. Choi O. R., Trainor C., Graf T., Beug H., Engel J. D. A single amino acid substitution in v-erbB confers a thermolabile phenotype to ts167 avian erythroblastosis virus-transformed erythroid cells. Mol Cell Biol. 1986 May;6(5):1751–1759. doi: 10.1128/mcb.6.5.1751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cohen S. Purification of the receptor for epidermal growth factor from A-431 cells: its function as a tyrosyl kinase. Methods Enzymol. 1983;99:379–387. doi: 10.1016/0076-6879(83)99074-2. [DOI] [PubMed] [Google Scholar]
  7. Di Fiore P. P., Pierce J. H., Fleming T. P., Hazan R., Ullrich A., King C. R., Schlessinger J., Aaronson S. A. Overexpression of the human EGF receptor confers an EGF-dependent transformed phenotype to NIH 3T3 cells. Cell. 1987 Dec 24;51(6):1063–1070. doi: 10.1016/0092-8674(87)90592-7. [DOI] [PubMed] [Google Scholar]
  8. Downward J., Yarden Y., Mayes E., Scrace G., Totty N., Stockwell P., Ullrich A., Schlessinger J., Waterfield M. D. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature. 1984 Feb 9;307(5951):521–527. doi: 10.1038/307521a0. [DOI] [PubMed] [Google Scholar]
  9. Duncan M. R., Stanish S. M., Cox D. C. Differential sensitivity of normal and transformed human cells to reovirus infection. J Virol. 1978 Nov;28(2):444–449. doi: 10.1128/jvi.28.2.444-449.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dustin M. L., Rothlein R., Bhan A. K., Dinarello C. A., Springer T. A. Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol. 1986 Jul 1;137(1):245–254. [PubMed] [Google Scholar]
  11. Dörig R. E., Marcil A., Chopra A., Richardson C. D. The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell. 1993 Oct 22;75(2):295–305. doi: 10.1016/0092-8674(93)80071-l. [DOI] [PubMed] [Google Scholar]
  12. Freistadt M. S., Kaplan G., Racaniello V. R. Heterogeneous expression of poliovirus receptor-related proteins in human cells and tissues. Mol Cell Biol. 1990 Nov;10(11):5700–5706. doi: 10.1128/mcb.10.11.5700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fung Y. K., Lewis W. G., Crittenden L. B., Kung H. J. Activation of the cellular oncogene c-erbB by LTR insertion: molecular basis for induction of erythroblastosis by avian leukosis virus. Cell. 1983 Jun;33(2):357–368. doi: 10.1016/0092-8674(83)90417-8. [DOI] [PubMed] [Google Scholar]
  14. Galán J. E., Pace J., Hayman M. J. Involvement of the epidermal growth factor receptor in the invasion of cultured mammalian cells by Salmonella typhimurium. Nature. 1992 Jun 18;357(6379):588–589. doi: 10.1038/357588a0. [DOI] [PubMed] [Google Scholar]
  15. Gamett D. C., Tracy S. E., Robinson H. L. Differences in sequences encoding the carboxyl-terminal domain of the epidermal growth factor receptor correlate with differences in the disease potential of viral erbB genes. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6053–6057. doi: 10.1073/pnas.83.16.6053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gentsch J. R., Pacitti A. F. Differential interaction of reovirus type 3 with sialylated receptor components on animal cells. Virology. 1987 Nov;161(1):245–248. doi: 10.1016/0042-6822(87)90192-9. [DOI] [PubMed] [Google Scholar]
  17. Gentsch J. R., Pacitti A. F. Effect of neuraminidase treatment of cells and effect of soluble glycoproteins on type 3 reovirus attachment to murine L cells. J Virol. 1985 Nov;56(2):356–364. doi: 10.1128/jvi.56.2.356-364.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Greve J. M., Davis G., Meyer A. M., Forte C. P., Yost S. C., Marlor C. W., Kamarck M. E., McClelland A. The major human rhinovirus receptor is ICAM-1. Cell. 1989 Mar 10;56(5):839–847. doi: 10.1016/0092-8674(89)90688-0. [DOI] [PubMed] [Google Scholar]
  19. Hashiro G., Loh P. C., Yau J. T. The preferential cytotoxicity of reovirus for certain transformed cell lines. Arch Virol. 1977;54(4):307–315. doi: 10.1007/BF01314776. [DOI] [PubMed] [Google Scholar]
  20. Hu B. R., Yang Y. B., Wieloch T. Depression of neuronal protein synthesis initiation by protein tyrosine kinase inhibitors. J Neurochem. 1993 Nov;61(5):1789–1794. doi: 10.1111/j.1471-4159.1993.tb09817.x. [DOI] [PubMed] [Google Scholar]
  21. Massoglia S., Gray A., Dull T. J., Munemitsu S., Kun H. J., Schlessinger J., Ullrich A. Epidermal growth factor receptor cytoplasmic domain mutations trigger ligand-independent transformation. Mol Cell Biol. 1990 Jun;10(6):3048–3055. doi: 10.1128/mcb.10.6.3048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mendelsohn C., Johnson B., Lionetti K. A., Nobis P., Wimmer E., Racaniello V. R. Transformation of a human poliovirus receptor gene into mouse cells. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7845–7849. doi: 10.1073/pnas.83.20.7845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Miles B. D., Robinson H. L. High-frequency transduction of c-erbB in avian leukosis virus-induced erythroblastosis. J Virol. 1985 May;54(2):295–303. doi: 10.1128/jvi.54.2.295-303.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Naniche D., Varior-Krishnan G., Cervoni F., Wild T. F., Rossi B., Rabourdin-Combe C., Gerlier D. Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus. J Virol. 1993 Oct;67(10):6025–6032. doi: 10.1128/jvi.67.10.6025-6032.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pace J., Hayman M. J., Galán J. E. Signal transduction and invasion of epithelial cells by S. typhimurium. Cell. 1993 Feb 26;72(4):505–514. doi: 10.1016/0092-8674(93)90070-7. [DOI] [PubMed] [Google Scholar]
  26. Pain B., Woods C. M., Saez J., Flickinger T., Raines M., Peyrol S., Moscovici C., Moscovici M. G., Kung H. J., Jurdic P. EGF-R as a hemopoietic growth factor receptor: the c-erbB product is present in chicken erythrocytic progenitors and controls their self-renewal. Cell. 1991 Apr 5;65(1):37–46. doi: 10.1016/0092-8674(91)90405-n. [DOI] [PubMed] [Google Scholar]
  27. Paul R. W., Choi A. H., Lee P. W. The alpha-anomeric form of sialic acid is the minimal receptor determinant recognized by reovirus. Virology. 1989 Sep;172(1):382–385. doi: 10.1016/0042-6822(89)90146-3. [DOI] [PubMed] [Google Scholar]
  28. Raines M. A., Lewis W. G., Crittenden L. B., Kung H. J. c-erbB activation in avian leukosis virus-induced erythroblastosis: clustered integration sites and the arrangement of provirus in the c-erbB alleles. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2287–2291. doi: 10.1073/pnas.82.8.2287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rommelaere J., Cornelis J. J. Antineoplastic activity of parvoviruses. J Virol Methods. 1991 Aug;33(3):233–251. doi: 10.1016/0166-0934(91)90024-t. [DOI] [PubMed] [Google Scholar]
  30. Rosenshine I., Ruschkowski S., Foubister V., Finlay B. B. Salmonella typhimurium invasion of epithelial cells: role of induced host cell tyrosine protein phosphorylation. Infect Immun. 1994 Nov;62(11):4969–4974. doi: 10.1128/iai.62.11.4969-4974.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shu H. K., Pelley R. J., Kung H. J. Dissecting the activating mutations in v-erbB of avian erythroblastosis virus strain R. J Virol. 1991 Nov;65(11):6173–6180. doi: 10.1128/jvi.65.11.6173-6180.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Shu H. K., Pelley R. J., Kung H. J. Tissue-specific transformation by epidermal growth factor receptor: a single point mutation within the ATP-binding pocket of the erbB product increases its intrinsic kinase activity and activates its sarcomagenic potential. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9103–9107. doi: 10.1073/pnas.87.23.9103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Staunton D. E., Merluzzi V. J., Rothlein R., Barton R., Marlin S. D., Springer T. A. A cell adhesion molecule, ICAM-1, is the major surface receptor for rhinoviruses. Cell. 1989 Mar 10;56(5):849–853. doi: 10.1016/0092-8674(89)90689-2. [DOI] [PubMed] [Google Scholar]
  34. Strong J. E., Tang D., Lee P. W. Evidence that the epidermal growth factor receptor on host cells confers reovirus infection efficiency. Virology. 1993 Nov;197(1):405–411. doi: 10.1006/viro.1993.1602. [DOI] [PubMed] [Google Scholar]
  35. Tang D., Strong J. E., Lee P. W. Recognition of the epidermal growth factor receptor by reovirus. Virology. 1993 Nov;197(1):412–414. doi: 10.1006/viro.1993.1603. [DOI] [PubMed] [Google Scholar]
  36. Ullrich A., Coussens L., Hayflick J. S., Dull T. J., Gray A., Tam A. W., Lee J., Yarden Y., Libermann T. A., Schlessinger J. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. 1984 May 31-Jun 6Nature. 309(5967):418–425. doi: 10.1038/309418a0. [DOI] [PubMed] [Google Scholar]
  37. Velu T. J., Beguinot L., Vass W. C., Willingham M. C., Merlino G. T., Pastan I., Lowy D. R. Epidermal-growth-factor-dependent transformation by a human EGF receptor proto-oncogene. Science. 1987 Dec 4;238(4832):1408–1410. doi: 10.1126/science.3500513. [DOI] [PubMed] [Google Scholar]
  38. Yamamoto T., Nishida T., Miyajima N., Kawai S., Ooi T., Toyoshima K. The erbB gene of avian erythroblastosis virus is a member of the src gene family. Cell. 1983 Nov;35(1):71–78. doi: 10.1016/0092-8674(83)90209-x. [DOI] [PubMed] [Google Scholar]
  39. Yura Y., Yoshida H., Sato M. Inhibition of herpes simplex virus replication by genistein, an inhibitor of protein-tyrosine kinase. Arch Virol. 1993;132(3-4):451–461. doi: 10.1007/BF01309554. [DOI] [PubMed] [Google Scholar]

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