1887

Abstract

CD46 (membrane cofactor protein; MCP) is a molecule that functions as either a complement-regulatory protein (CRP) or a receptor for some pathogens, including human herpesvirus 6. DNA microarray analysis suggested that the expression of CD46 was upregulated in T cells infected with human herpesvirus 7 (HHV-7). Northen and Western blot analyses supported this result at both the transcriptional and translational levels. Flow-cytometric analysis revealed that upregulation of CD46 occurred at a late stage of infection in both SupT1 cells and primary CD4 T cells, and also that expression of another CRP, CD59, was increased at a late stage of infection. Whether these CRPs actually function in HHV-7-infected cells was addressed and it was found that HHV-7-infected cells were more resistant to complement-dependent cytotoxicity than were uninfected cells. This study is the first report demonstrating that HHV-7 infection causes elevation of the CRPs CD46 and CD59, which may be a possible mechanism for HHV-7 to evade humoral immunity via complement.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.82394-0
2007-05-01
2021-01-23
Loading full text...

Full text loading...

/deliver/fulltext/jgv/88/5/1415.html?itemId=/content/journal/jgv/10.1099/vir.0.82394-0&mimeType=html&fmt=ahah

References

  1. Berneman Z. N., Ablashi D. V., Li G., Eger-Fletcher M., Reitz M. S. Jr, Hung C. L., Brus I., Komaroff A. L., Gallo R. C. 1992; Human herpesvirus 7 is a T-lymphotropic virus and is related to, but significantly different from, human herpesvirus 6 and human cytomegalovirus. Proc Natl Acad Sci U S A 89:10552–10556 [CrossRef]
    [Google Scholar]
  2. Devaux P., Christiansen D., Fontaine M., Gerlier D. 1999; Control of C3b and C5b deposition by CD46 (membrane cofactor protein) after alternative but not classical complement activation. Eur J Immunol 29:815–822 [CrossRef]
    [Google Scholar]
  3. Dorig R. E., Marcil A., Chopra A., Richardson C. D. 1993; The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell 75:295–305 [CrossRef]
    [Google Scholar]
  4. Foa-Tomasi L., Avitabile E., Ke L., Campadelli-Fiume G. 1994; Polyvalent and monoclonal antibodies identify major immunogenic proteins specific for human herpesvirus 7-infected cells and have weak cross-reactivity with human herpesvirus 6. J Gen Virol 75:2719–2727 [CrossRef]
    [Google Scholar]
  5. Fodor W. L., Rollins S. A., Bianco-Caron S., Rother R. P., Guilmette E. R., Burton W. V., Albrecht J. C., Fleckenstein B., Squinto S. P. 1995; The complement control protein homolog of herpesvirus saimiri regulates serum complement by inhibiting C3 convertase activity. J Virol 69:3889–3892
    [Google Scholar]
  6. Frenkel N., Schirmer E. C., Wyatt L. S., Katsafanas G., Roffman E., Danovich R. M., June C. H. 1990; Isolation of a new herpesvirus from human CD4+ T cells. Proc Natl Acad Sci U S A 87:748–752 [CrossRef]
    [Google Scholar]
  7. Friedman H. M., Cohen G. H., Eisenberg R. J., Seidel C. A., Cines D. B. 1984; Glycoprotein C of herpes simplex virus 1 acts as a receptor for the C3b complement component on infected cells. Nature 309:633–635 [CrossRef]
    [Google Scholar]
  8. Gaggar A., Shayakhmetov D. M., Lieber A. 2003; CD46 is a cellular receptor for group B adenoviruses. Nat Med 9:1408–1412 [CrossRef]
    [Google Scholar]
  9. Kallstrom H., Liszewski M. K., Atkinson J. P., Jonsson A. B. 1997; Membrane cofactor protein (MCP or CD46) is a cellular pilus receptor for pathogenic Neisseria. Mol Microbiol 25:639–647 [CrossRef]
    [Google Scholar]
  10. Kapadia S. B., Molina H., van Berkel V., Speck S. H., Virgin H. W. IV 1999; Murine gammaherpesvirus 68 encodes a functional regulator of complement activation. J Virol 73:7658–7670
    [Google Scholar]
  11. Kemper C., Chan A. C., Green J. M., Brett K. A., Murphy K. M., Atkinson J. P. 2003; Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype. Nature 421:388–392 [CrossRef]
    [Google Scholar]
  12. Kojima A., Iwata K., Seya T., Matsumoto M., Ariga H., Atkinson J. P., Nagasawa S. 1993; Membrane cofactor protein (CD46) protects cells predominantly from alternative complement pathway-mediated C3-fragment deposition and cytolysis. J Immunol 151:1519–1527
    [Google Scholar]
  13. Liszewski M. K., Atkinson J. P. 1996; Membrane cofactor protein (MCP; CD46). Isoforms differ in protection against the classical pathway of complement. J Immunol 156:4415–4421
    [Google Scholar]
  14. Loor F. 1984; Ligand-induced patching and capping of surface immunoglobulins. Methods Enzymol 108:371–385
    [Google Scholar]
  15. Loveland B. E., Johnstone R. W., Russell S. M., Thorley B. R., McKenzie I. F. 1993; Different membrane cofactor protein (CD46) isoforms protect transfected cells against antibody and complement mediated lysis. Transpl Immunol 1:101–108 [CrossRef]
    [Google Scholar]
  16. Lusso P., Secchiero P., Crowley R. W., Garzino-Demo A., Berneman Z. N., Gallo R. C. 1994; CD4 is a critical component of the receptor for human herpesvirus 7: interference with human immunodeficiency virus. Proc Natl Acad Sci U S A 91:3872–3876 [CrossRef]
    [Google Scholar]
  17. McNearney T. A., Odell C., Holers V. M., Spear P. G., Atkinson J. P. 1987; Herpes simplex virus glycoproteins gC-1 and gC-2 bind to the third component of complement and provide protection against complement-mediated neutralization of viral infectivity. J Exp Med 166:1525–1535 [CrossRef]
    [Google Scholar]
  18. Miyagawa S., Shirakura R., Iwata K., Nakata S., Matsumiya G., Izutani H., Matsuda H., Terado A., Matsumoto M. other authors 1994; Effects of transfected complement regulatory proteins, MCP, DAF, and MCP/DAE hybrid, on complement-mediated swine endothelial cell lysis. Transplantation 58:834–840 [CrossRef]
    [Google Scholar]
  19. Nakagawa N., Mukai T., Sakamoto J., Hata A., Okuno T., Takeda K., Yamanishi K. 1997; Antigenic analysis of human herpesvirus 7 (HHV-7) and HHV-6 using immune sera and monoclonal antibodies against HHV-7. J Gen Virol 78:1131–1137
    [Google Scholar]
  20. Naniche D., Varior-Krishnan G., Cervoni F., Wild T. F., Rossi B., Rabourdin-Combe C., Gerlier D. 1993; Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus. J Virol 67:6025–6032
    [Google Scholar]
  21. Nicholas J. 1996; Determination and analysis of the complete nucleotide sequence of human herpesvirus. J Virol 70:5975–5989
    [Google Scholar]
  22. Nomura M., Kurita-Taniguchi M., Kondo K., Inoue N., Matsumoto M., Yamanishi K., Okabe M., Seya T. 2002; Mechanism of host cell protection from complement in murine cytomegalovirus (CMV) infection: identification of a CMV-responsive element in the CD46 promoter region. Eur J Immunol 32:2954–2964 [CrossRef]
    [Google Scholar]
  23. Oglesby T. J., Allen C. J., Liszewski M. K., White D. J., Atkinson J. P. 1992; Membrane cofactor protein (CD46) protects cells from complement-mediated attack by an intrinsic mechanism. J Exp Med 175:1547–1551 [CrossRef]
    [Google Scholar]
  24. Okada N., Liszewski M. K., Atkinson J. P., Caparon M. 1995; Membrane cofactor protein (CD46) is a keratinocyte receptor for the M protein of the group A streptococcus. Proc Natl Acad Sci U S A 92:2489–2493 [CrossRef]
    [Google Scholar]
  25. Price J. D., Schaumburg J., Sandin C., Atkinson J. P., Lindahl G., Kemper C. 2005; Induction of a regulatory phenotype in human CD4+ T cells by streptococcal M protein. J Immunol 175:677–684 [CrossRef]
    [Google Scholar]
  26. Sadaoka T., Yamanishi K., Mori Y. 2006; Human herpesvirus 7 U47 gene products are glycoproteins expressed in virions and associate with glycoprotein H. J Gen Virol 87:501–508 [CrossRef]
    [Google Scholar]
  27. Santoro F., Kennedy P. E., Locatelli G., Malnati M. S., Berger E. A., Lusso P. 1999; CD46 is a cellular receptor for human herpesvirus 6. Cell 99:817–827 [CrossRef]
    [Google Scholar]
  28. Segerman A., Atkinson J. P., Marttila M., Dennerquist V., Wadell G., Arnberg N. 2003; Adenovirus type 11 uses CD46 as a cellular receptor. J Virol 77:9183–9191 [CrossRef]
    [Google Scholar]
  29. Seya T., Hara T., Matsumoto M., Akedo H. 1990; Quantitative analysis of membrane cofactor protein (MCP) of complement. High expression of MCP on human leukemia cell lines, which is down-regulated during cell differentiation. J Immunol 145:238–245
    [Google Scholar]
  30. Seya T., Okada M., Matsumoto M., Hong K. S., Kinoshita T., Atkinson J. P. 1991; Preferential inactivation of the C5 convertase of the alternative complement pathway by factor I and membrane cofactor protein (MCP). Mol Immunol 28:1137–1147 [CrossRef]
    [Google Scholar]
  31. Spiller O. B., Morgan B. P., Tufaro F., Devine D. V. 1996; Altered expression of host-encoded complement regulators on human cytomegalovirus-infected cells. Eur J Immunol 26:1532–1538 [CrossRef]
    [Google Scholar]
  32. Spiller O. B., Robinson M., O'Donnell E., Milligan S., Morgan B. P., Davison A. J., Blackbourn D. J. 2003; Complement regulation by Kaposi's sarcoma-associated herpesvirus ORF4 protein. J Virol 77:592–599 [CrossRef]
    [Google Scholar]
  33. Takeda K., Haque M., Nagoshi E., Takemoto M., Shimamoto T., Yoneda Y., Yamanishi K. 2000; Characterization of human herpesvirus 7 U27 gene product and identification of its nuclear localization signal. Virology 272:394–401 [CrossRef]
    [Google Scholar]
  34. Takemoto M., Shimamoto T., Isegawa Y., Yamanishi K. 2001; The R3 region, one of three major repetitive regions of human herpesvirus 6, is a strong enhancer of immediate-early gene U95. J Virol 75:10149–10160 [CrossRef]
    [Google Scholar]
  35. Tanaka K., Kondo T., Torigoe S., Okada S., Mukai T., Yamanishi K. 1994; Human herpesvirus 7: another causal agent for roseola (exanthem subitum). J Pediatr 125:1–5 [CrossRef]
    [Google Scholar]
  36. Tanaka-Taya K., Kondo T., Mukai T., Miyoshi H., Yamamoto Y., Okada S., Yamanishi K. 1996; Seroepidemiological study of human herpesvirus-6 and -7 in children of different ages and detection of these two viruses in throat swabs by polymerase chain reaction. J Med Virol 48:88–94 [CrossRef]
    [Google Scholar]
  37. Wyatt L. S., Rodriguez W. J., Balachandran N., Frenkel N. 1991; Human herpesvirus 7: antigenic properties and prevalence in children and adults. J Virol 65:6260–6265
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.82394-0
Loading
/content/journal/jgv/10.1099/vir.0.82394-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error