Download PDF
Thromb Haemost 2009; 102(06): 1050-1056
DOI: 10.1160/TH09-03-0202
Theme Issue Article
Schattauer GmbH

Systemic spread of measles virus: Overcoming the epithelial and endothelial barriers

Martin Ludlow
1   Department of Molecular Virology, School of Medicine, Dentistry and Biomedical Sciences, The Queen’s University of Belfast, Belfast, UK
,
Ingrid Allen
1   Department of Molecular Virology, School of Medicine, Dentistry and Biomedical Sciences, The Queen’s University of Belfast, Belfast, UK
,
Jürgen Schneider-Schaulies
2   Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany
› Author Affiliations
Further Information

Publication History

Received: 06 June 2009

Accepted after revision: 19 June 2009

Publication Date:
28 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

As the major entry receptor, signalling lymphocytic activation molecule (SLAM, CD150) essentially determines the tropism of measles virus (MV) for immune cells. This receptor is of considerable importance for the induction of immunomodulation and -suppression, and for the systemic spread of MV to organs including secondary lymphoid tissues, the skin, the respiratory tract, and the brain predominantly via infected cells of the immune system. But how does the virus cross the epithelial barrier during initiation of the infection, the blood organ barriers formed by endothelial cells, and the epithelial barrier from within, when virus will be released from the host? Additional unknown receptor(s) on CD150-negative epithelial and endothelial cells have been postulated. However, it has also been postulated (and demonstrated in macaques) that the initial infection is independent from usage of this receptor, and that the first target cells appear to be CD150-positive cells in the epithelium. For later stages of the infection, for virus release from the host, it is claimed that this unknown receptor on epithelial cells is required for crossing the barrier from within. The endothelial cell barrier must be crossed from the apical (luminal) to the basolateral (abluminal) side to carry the infection to organs and the skin. However, infected leukocytes are impaired in several functions including transmigration through endothelial cells. The infection may spread via cell contact-mediated infection of endothelial cells and basolateral virus release, or via migration of infected leukocytes.

Keywords

Viral infection - cerebrovascular disease - receptors
 

  • References

  • 1 WHO. Progress in global measles control and mortality reduction, 2000–2007. Wkly Epidemiol Rec 2008; 83: 441-448.
    PubMedGoogle Scholar
  • 2 Katz M. Clinical spectrum of measles. In: lBilleter MA, ter Meulen v. editors. Measles Virus. Berlin, Heidelberg, New York: Springer-Verlag; 1995: 1-12.
    Google Scholar
  • 3 von Pirquet C. Das Verhalten der kutanen Tuberkulin-Reaktion während der Masern. Dt Med Wochenschr 1908; 34: 1297-1300.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Borrow P, Oldstone MBA. Measles virus-mononu-clear cell interactions. In: Billeter MA, ter Meulen V. editors. Measles Virus. Berlin, Heidelberg, New York: Springer-Verlag; 1995: 85-100.
    Google Scholar
  • 5 Griffin DE. Immune responses during measles virus infection. In: Billeter MA, ter Meulen V. editors. Measles Virus. Berlin, Heidelberg, New York: Springer-Verlag; 1995: 117-134.
    Google Scholar
  • 6 Schneider-Schaulies J, ter Meulen V, Schneider-Schaulies S. Measles virus interactions with cellular receptors: Consequences for viral pathogenesis. J Neurovirol 2001; 07: 391-399.
    CrossrefPubMedGoogle Scholar
  • 7 Okada H, Kobune F, Sato TA. et al. Extensive lymphopenia due to apoptosis of uninfected lymphocytes in acute measles patients. Arch Virol 2000; 145: 905-920.
    CrossrefPubMedGoogle Scholar
  • 8 Okada H, Sato T, Katayama A. et al. Comparative analysis of host responses related to immunosuppression between measles patients and vaccine recipients with live attenuated measles vaccines. Arch Virol 2001; 146: 859-874.
    CrossrefPubMedGoogle Scholar
  • 9 Arneborn P, Biberfeld G. T-lymphocyte subpopulations in relation to immunosuppression in measles and varicella. Infection and Immunity 1983; 39: 29-37.
    PubMedGoogle Scholar
  • 10 Ryon JJ, Moss WJ, Monze M. et al. Functional and phenotypic changes in circulating lymphocytes from hospitalized zambian children with measles. Clin Diagn Lab Immunol 2002; 09: 994-1003.
    PubMedGoogle Scholar
  • 11 Fugier-Vivier I, Servet-Delprat C, Rivailler P. et al. Measles virus suppresses cell-mediated immunity by interfering with the survival and functions of dendritic and T cells. J Exp Med 1997; 186: 813-823.
    CrossrefPubMedGoogle Scholar
  • 12 Grosjean I, Caux C, Bella C. et al. Measles virus infects human dendritic cells and blocks their allostimulatory properties for CD4+ T cells. J Exp Med 1997; 186: 801-812.
    CrossrefPubMedGoogle Scholar
  • 13 Servet-Delprat C, Vidalain PO, Azocar O. et al. Consequences of Fas-mediated human dendritic cell apoptosis induced by measles virus. J Virol 2000; 74: 4387-4393.
    CrossrefPubMedGoogle Scholar
  • 14 Vidalain PO, Azocar O, Lamouille B. et al. Measles virus induces functional TRAIL production by human dendritic cells. J Virol 2000; 74: 556-559.
    CrossrefPubMedGoogle Scholar
  • 15 Vidalain PO, Azocar O, Rabourdin-Combe C. et al. Measles virus-infected dendritic cells develop immunosuppressive and cytotoxic activities. Immunobiology 2001; 204: 629-638.
    CrossrefPubMedGoogle Scholar
  • 16 Nanan R, Chittka B, Hadam M. et al. Measles virus infection causes transient depletion of activated T cells from peripheral circulation. J Clin Virol 1999; 12: 201-210.
    CrossrefPubMedGoogle Scholar
  • 17 Bellini WJ, Rota JS, Lowe LE. et al. Subacute sclerosing panencephalitis: More cases of this fatal disease are prevented by measles immunization than previously recognized. J Infect Dis 2005; 192: 1686-1693.
    CrossrefPubMedGoogle Scholar
  • 18 Weissbrich B, Schneider-Schaulies J, ter Meulen V. Measles and its neurological complications. New York: Marcel Dekker; 2003
    Google Scholar
  • 19 Cathomen T, Naim HY, Cattaneo R. Measles viruses with altered envelope protein cytoplasmic tails gain cell fusion competence. J Virol 1998; 72: 1224-1234.
    PubMedGoogle Scholar
  • 20 Cathomen T, Mrkic B, Spehner D. et al. A matrixless measles virus is infectious and elicits extensive cell fusion: consequences for propagation in the brain. EMBO J 1998; 17: 3899-3908.
    CrossrefPubMedGoogle Scholar
  • 21 Pohl C, Duprex WP, Krohne G. et al. Measles virus M and F proteins associate with detergent-resistant membrane fractions and promote formation of viruslike particles. J Gen Virol 2007; 88: 1243-1250.
    CrossrefPubMedGoogle Scholar
  • 22 Reuter T, Weissbrich B, Schneider-Schaulies S. et al. RNA interference with measles virus N-, P-, and L-mRNAs efficiently prevents, and with matrix protein-mRNA enjances viral transcription. J Virol 2006; 80: 5951-5957.
    CrossrefPubMedGoogle Scholar
  • 23 Colf LA, Juo ZS, Garcia KC. Structure of the measles virus hemagglutinin. Nat Struct Mol Biol 2007; 14: 1227-1228.
    CrossrefPubMedGoogle Scholar
  • 24 Hashiguchi T, Kajikawa M, Maita N. et al. Crystal structure of measles virus hemagglutinin provides insight into effective vaccines. Proc Natl Acad Sci U S A 2007; 104: 19535-19540.
    CrossrefPubMedGoogle Scholar
  • 25 Dörig RE, Marcil A, Chopra A. et al. The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell 1993; 75: 295-305.
    CrossrefPubMedGoogle Scholar
  • 26 Naniche D, Varior-Krishnan G, Cervoni F. et al. Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus. J Virol 1993; 67: 6025-6032.
    PubMedGoogle Scholar
  • 27 Schneider-Schaulies J, Schnorr JJ, Brinckmann U. et al. Receptor usage and differential downregulation of CD46 by measles virus wild-type and vaccine strains. Proc Natl Acad Sci U S A 1995; 92: 3943-3947.
    CrossrefPubMedGoogle Scholar
  • 28 Schnorr JJ, Dunster LM, Nanan R. et al. Measles virus-induced down-regulation of CD46 is associated with enhanced sensitivity to complement-mediated lysis of infected cells. Eur J Immunol 1995; 25: 976-984.
    CrossrefPubMedGoogle Scholar
  • 29 Erlenhoefer C, Wurzer WJ, Löffler S. et al. CD150 (SLAM) is a receptor for measles virus, but is not involved in viral contact-mediated proliferation inhibition. J Virol 2001; 75: 4499-4505.
    CrossrefPubMedGoogle Scholar
  • 30 Hsu EC, Iorio C, Sarangi F. et al. CDw150(SLAM) is a receptor for a lymphotropic strain of measles virus and may account for the immunosuppressive properties of this virus. Virology 2001; 279: 9-21.
    CrossrefPubMedGoogle Scholar
  • 31 Tatsuo H, Ono N, Tanaka K. et al. SLAM (CDw150) is a cellular receptor for measles virus. Nature 2000; 406: 893-897.
    CrossrefPubMedGoogle Scholar
  • 32 Tatsuo H, Ono N, Yanagi Y. Morbilliviruses use signalling lymphocyte activation molecules (CD150) as cellular receptors. J Virol 2001; 75: 5842-5850.
    CrossrefPubMedGoogle Scholar
  • 33 Ono N, Tatsuo H, Tanaka K. et al. V domain of human SLAM (CDw150) is essential for its function as a measles virus receptor. J Virol 2001; 75: 1594-1600.
    CrossrefPubMedGoogle Scholar
  • 34 Yanagi Y, Takeda M, Ohno S. Measles virus: cellular receptors, tropism and pathogenesis. J Gen Virol 2006; 87: 2767-2779.
    CrossrefPubMedGoogle Scholar
  • 35 Baron MD. Wild-type Rinderpest virus uses SLAM (CD150) as its receptor. J Gen Virol 2005; 86: 1753-1757.
    CrossrefPubMedGoogle Scholar
  • 36 Tatsuo H, Yanagi Y. The morbillivirus receptor SLAM (CD150). Microbiol Immunol 2002; 46: 135-142.
    CrossrefPubMedGoogle Scholar
  • 37 Browning MB, Woodliff JE, Konkol MC. et al. The T cell activation marker CD150 can be used to identify alloantigen-activated CD4+25+ regulatory T cells. Cell Immunol 2004; 227: 129-139.
    CrossrefPubMedGoogle Scholar
  • 38 Aversa G, Chang C-CJ, Carballido JM. Engagement of the signalling lymphocytic activation molecule (SLAM) on activated T cells results in IL-2-indepen- dent, cyclosporin A-sensitive T cell proliferation and IFN-gamma production. J Immunol 1997; 158: 4036-4044.
    PubMedGoogle Scholar
  • 39 Condack C, Grivel JC, Devaux P. et al. Measles virus vaccine attenuation: suboptimal infection of lymphatic tissue and tropism alteration. J Infect Dis 2007; 196: 541-549.
    CrossrefPubMedGoogle Scholar
  • 40 de Swart RL, Ludlow M, de Witte L. et al. Predominant Infection of CD150(+) Lymphocytes and Dendritic Cells during Measles Virus Infection of Macaques. PLoS Pathog 2007; 03: e178.
    CrossrefPubMedGoogle Scholar
  • 41 Esolen LM, Ward BJ, Moench TR. et al. Infection of moncytes during measles. J Infect Dis 1993; 168: 47-52.
    CrossrefPubMedGoogle Scholar
  • 42 Minagawa H, Tanaka K, Ono N. et al. Induction of the measles virus receptor SLAM (CD150) on monocytes. J Gen Virol 2001; 82: 2913-2917.
    CrossrefPubMedGoogle Scholar
  • 43 Kruse M, Meinl E, Henning G. et al. Signaling lymphocytic activation molecule is expressed on mature CD83+ dendritic cells and is up-regulated by IL-1b. J Immunol 2001; 167: 1989-1995.
    CrossrefPubMedGoogle Scholar
  • 44 Welstead GG, Hsu EC, Iorio C. et al. Mechanism of CD150 (SLAM) down regulation from the host cell surface by measles virus hemagglutinin protein. J Virol 2004; 78: 9666-9674.
    CrossrefPubMedGoogle Scholar
  • 45 Mikhalp SV, Shlapatska LM, Berdowa AG. et al. CDw150 associates with Src-homology 2-containing inositol phosphatase and modulates CD95-mediated apoptosis. J Immunol 1999; 162: 5719-5727.
    PubMedGoogle Scholar
  • 46 Cocks BG, Chang C-CJ, Carballido JM. et al. A novel receptor involved in T-cell activation. Nature 1995; 376: 260-263.
    CrossrefPubMedGoogle Scholar
  • 47 Engel P, Eck MJ, Terhost C. The SAP and SLAM families in immune response and X-linked lymphoproliferative disease. Nat Rev Immunol 2003; 03: 813-821.
    CrossrefPubMedGoogle Scholar
  • 48 Sidorenko SP, Clark EA. The dual-function CD150 receptor subfamily: the viral attraction. Nat Immunol 2003; 04: 19-24.
    CrossrefPubMedGoogle Scholar
  • 49 Wang N, Satoskar A, Faubion W. et al. The cell surface recepor SLAM controls T cell and macrophage functions. J Exp Med 2004; 199: 1255-1264.
    CrossrefPubMedGoogle Scholar
  • 50 Andres O, Obojes K, Kim KS. et al. CD46- and CD150-independent endothelial cell infection with wild-type measles viruses. J Gen Virol 2003; 84: 1189-1197.
    CrossrefPubMedGoogle Scholar
  • 51 Takeuchi K, Miyajima N, Nagata N. et al. Wild-type measles virus induces large syncytium formation in primary human small airway epithelial cells by a SLAM(CD150)-independent mechanism. Virus Res 2003; 94: 11-16.
    CrossrefPubMedGoogle Scholar
  • 52 Takeda M, Tahara M, Hashiguchi T. et al. A human lung carcinoma cell line supports efficient measles virus growth and syncytium formation via a SLAMand CD46-independent mechanism. J Virol 2007; 81: 12091-12096.
    CrossrefPubMedGoogle Scholar
  • 53 Dunster LM, Schneider-Schaulies J, Loffler S. et al. Moesin: a cell membrane protein linked with susceptibility to measles virus infection. Virology 1994; 198: 265-274.
    CrossrefPubMedGoogle Scholar
  • 54 Harrowe G, Sudduth-Klinger J, Payan DG. Measles virus-substance P receptor interaction: Jurkat lymphocytes transfected with substance P receptor cDNA enhance measles virus fusion and replication. Cell Mol Neurobiol 1992; 12: 397-409.
    CrossrefPubMedGoogle Scholar
  • 55 Bieback K, Lien E, Klagge I. et al. The hemagglutinin protein of wild-type measles virus activates Toll-like receptor 2 signaling. J Virol 2002; 76: 8729-8736.
    CrossrefPubMedGoogle Scholar
  • 56 Ravanel K, Castelle C, Defrance T. et al. Measles virus nucleocapsid protein binds to FcgammaRII and inhibits human B cell antibody production. J Exp Med 1997; 186: 269-278.
    CrossrefPubMedGoogle Scholar
  • 57 de Witte L, Abt M, Schneider-Schaulies S. et al. Measles virus targets DC-SIGN to enhance dendritic cell infection. J Virol 2006; 80: 3477-3486.
    CrossrefPubMedGoogle Scholar
  • 58 de Witte L, de Vries RD, van der Vlist M. et al. DCSIGN and CD150 have distinct roles in transmission of measles virus from dendritic cells to T-lymphocytes. PLoS Pathog 2008; 04: e1000049.
    CrossrefPubMedGoogle Scholar
  • 59 Tahara M, Takeda M, Shirogane Y. et al. Measles virus infects both polarized epithelial and immune cells by using distinctive receptor-binding sites on its hemagglutinin. J Virol 2008; 82: 4630-4637.
    CrossrefPubMedGoogle Scholar
  • 60 Leonard VH, Sinn PL, Hodge G. et al. Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed. J Clin Invest 2008; 118: 2448-2458.
    PubMedGoogle Scholar
  • 61 Forthal DN, Aarnaes S, Blanding J. et al. Degree and length of viremia in adults with measles. J Infect Dis 1992; 166: 421-424.
    CrossrefPubMedGoogle Scholar
  • 62 Schneider-Schaulies S, Kreth HW, Hofmann G. et al. Expression of measles virus RNA in peripheral blood mononuclear cells of patients with measles, SSPE, and autoimmune diseases. Virology 1991; 182: 703-711.
    CrossrefPubMedGoogle Scholar
  • 63 von Messling V, Milosevic D, Cattaneo R. Tropism illuminated: lymphocyte-based pathways blazed by lethal morbillivirus through the host immune system. Proc Natl Acad Sci U S A 2004; 101: 14216-14221.
    CrossrefPubMedGoogle Scholar
  • 64 Niewiesk S, Eisenhuth I, Fooks A. et al. Measles virus-induced immune suppression in the cotton rat (Sigmodon hispidus) model depends on viral glycoproteins. J Virol 1997; 71: 7214-7219.
    PubMedGoogle Scholar
  • 65 Pfeuffer J, Püschel K, ter Meulen V. et al. Extent of measles virus spread and immune suppression differentiates between wild-type and vaccine strains in the cotton rat model (sigmodon hispidus). J Virol 2003; 77: 150-158.
    CrossrefPubMedGoogle Scholar
  • 66 Wyde PR, Ambrosi MW, Voss TG. et al. Measles virus replication in lungs of hispid cotton rats after intranasal inoculation. Proc Soc Exp Biol Med 1992; 201: 80-87.
    CrossrefPubMedGoogle Scholar
  • 67 Hahm B, Arbour N, Oldstone MB. Measles virus interacts with human SLAM receptor on dendritic cells to cause immunosuppression. Virology 2004; 323: 292-302.
    CrossrefPubMedGoogle Scholar
  • 68 Hahm B, Cho JH, Oldstone MB. Measles virusdendritic cell interaction via SLAM inhibits innate immunity: selective signaling through TLR4 but not other TLRs mediates suppression of IL-12 synthesis. Virology 2007; 358: 251-257.
    CrossrefPubMedGoogle Scholar
  • 69 Haines DM, Martin KM, Chelack BJ. et al. Immunohistochemical detection of canine distemper virus in haired skin, nasal mucosa, and footpad epithelium: a method for antemortem diagnosis of infection. J Vet Diagn Invest 1999; 11: 396-399.
    CrossrefPubMedGoogle Scholar
  • 70 Kimura A, Tosaka K, Nakao T. Measles rash I. Light and electron microscopicstudy of skin eruptions. Archives of Virol 1975; 47: 295-307.
    PubMedGoogle Scholar
  • 71 Cosby SL, Brankin B. Measles virus infection of cerebral endothelial cells and effect on their adhesive properties. Veterinary Microbiology 1995; 44: 135-139.
    CrossrefPubMedGoogle Scholar
  • 72 Fournier JG, Tardieu M, Lebon P. et al. Detection of measles virus RNA in lymphocytes from peripheralblood and brain perivascular infiltrates of patients with subacute sclerosing panencephalitis. N Engl J Med 1985; 313: 910-915.
    CrossrefPubMedGoogle Scholar
  • 73 McQuaid S, Kirk J, Zhou AL. et al. Measles virus infection of cells in perivascular infiltrates in the brain in subacute sclerosing panencephalitis: confirmation by non-radioactive in situ hybridization, immunocytochemistry and electron microscopy. Acta Neuropathol 1993; 85: 154-158.
    PubMedGoogle Scholar
  • 74 Scheifele DW, Forbes CE. Prolonged giant cell excretion in severe African measles. Pediatrics 1972; 50: 867-873.
    PubMedGoogle Scholar
  • 75 Moench TR, Griffin DE, Obriecht CR. et al. Acute measles in patients with and without neurological involvement: distribution of measles virus antigen and RNA. J Infect Dis 1988; 158: 433-442.
    CrossrefPubMedGoogle Scholar
  • 76 Esolen LM, Takahashi K, Johnson RT. et al. Brain endothelial cell infection in children with acute fatal measles. J Clin Invest 1995; 96: 2478-2481.
    CrossrefPubMedGoogle Scholar
  • 77 Allen IV, McQuaid S, McMahon J. et al. The significance of measles virus antigen and genome distribution in the CNS in SSPE for mechanisms of viral spread and demyelination. J Neuropathol Exp Neurol 1996; 55: 471-480.
    CrossrefPubMedGoogle Scholar
  • 78 Isaacson SH, Asher DM, Godec MS. et al. Widespread, restricted low-level measles virus infection of brain in a case of subacute sclerosing panencephalitis. Acta Neuropathol 1996; 91: 135-139.
    CrossrefPubMedGoogle Scholar
  • 79 Kirk J, Zhou AL, McQuaid S. et al. Cerebral endothelial cell infection by measles virus in subacute sclerosing panencephalitis: ultrastructural and in situ hybridization evidence. Neuropathol Appl Neurobiol 1991; 17: 289-297.
    CrossrefPubMedGoogle Scholar
  • 80 Dittmar S, Harms H, Runkler N. et al. Measles virus-induced block of transendothelial migration of T lymphocytes and infection-mediated virus spread across endothelial cell barriers. J Virol 2008; 82: 11273-11282.
    CrossrefPubMedGoogle Scholar
  • 81 Oldstone MBA, Dales S, Tishon A. et al. A role for dual hits in causation of subacute sclerosing panencephalitis. J Exp Med 2005; 202: 1185-1190.
    CrossrefPubMedGoogle Scholar