Inmunomodulación del virus del sarampión (measles virus inmunomodulation)

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expert reviews

in molecular medicine

Measles virus and immunomodulation: molecular bases and perspectives
Sibylle Schneider-Schaulies and Volker ter Meulen
Measles virus (MV) remains among the most potent global pathogens, killing more than 1 million children annually. The virus induces a profound suppression of immune functions that favours theestablishment of, and aggravates the course of, secondary infections. By contrast, MV-specific immune responses are efficiently generated, and these clear the virus from the organism and confer a long-lasting immunity. As sensitisers of pathogen encounter and instructors of the adaptive immune response, professional antigen-presenting cells (APCs) such as dendritic cells play a decisive role in theinduction and quality of the MV-specific immune response. However, key features of immune suppression associated with MV are compatible with interference with APC maturation and function, and subsequent qualitative and quantitative alterations of T-cell activation.
Rated among the ten most frequent and deadly infectious diseases, measles is the most important vaccine-preventable clinical entity. The useof an efficient and safe live vaccine has resulted in the successful elimination of indigenous transmission of measles virus (MV) in the Americas, and has significantly reduced the number and magnitude of epidemics, morbidity and mortality in industrialised countries. There has been no such success in developing countries, where the vast majority of the more than 40 million cases of measles occur,including more than 1 million fatal cases of measles annually. These result from a transient suppression of immune functions by MV that favours the establishment of, and aggravates the course of, secondary infections. In infants under one year of age, maternal antibodies can decrease to levels where they are no longer protective against infection with wild-type measles but still interfere withsuccessful vaccination.

Pathogenesis, immune activation and suppression
Measles is spread by the respiratory route and causes a well-defined disease in seronegative individuals, usually early in childhood. Tissueresident macrophages or dendritic cells (DCs) in the respiratory mucosa may acquire virus directly or from the basolateral side of epithelial cells

Sibylle Schneider-Schaulies(corresponding author) Professor and Lecturer, Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany. Tel: +49 931 201 49895; Fax: +49 931 201 49553; E-mail: s-s-s@vim.uni-wuerzburg.de Volker ter Meulen Professor and Head of Department, Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany.Tel: +49 931 201 49554; Fax: +49 931 201 49553; E-mail: termeulen@vim.uni-wuerzburg.de
Accession information: (02)00469-6a.pdf (short code: txt001ssw); 30 May 2002 ISSN 1462-3994 ©2002 Cambridge University Press

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Measles virus and immunomodulation: molecular bases and perspectives

http://www.expertreviews.org/

expert reviews

in molecular medicine

(Ref. 1). After transport fromthe respiratory tract to the local lymphatic tissues, MV is amplified and spreads by a cell-associated viraemia. MV-specific RNA and proteins can be detected in a minor proportion of lymphocytes and monocytes during, and for a few days after, the measles rash (Refs 2, 3). The rash clearly marks the onset of immune responses as determined by the appearance of virus-specific T cells and antiviralantibodies. Initial immunoglobulin isotypes produced are IgM and IgA, followed later by IgG (mainly IgG1 and IgG4). Plasma IgE levels also rise, but there is no evidence that the IgE contains MV-specific antibody. A marked infiltration of mononuclear cells into local areas of viral replication is seen and virus-specific T cells appear in the blood. Plasma levels of the soluble T-cell surface...