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  • Authors: Manuel A. Franco1, Harry B. Greenberg2
  • Editors: James E. Crowe Jr.4, Diana Boraschi5, Rino Rappuoli6
    Affiliations: 1: Facultad de Ciencias y Medicina, Pontificia Universidad Javeriana, Bogotá, Colombia; 2: Departments of Medicine and Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305; 3: Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304; 4: Vanderbilt University School of Medicine, Nashville, TN; 5: National Research Council, Pisa, Italy; 6: Novartis Vaccines, Siena, Italy
  • Source: microbiolspec December 2013 vol. 1 no. 2 doi:10.1128/microbiolspec.AID-0011-2013
  • Received 23 February 2013 Accepted 08 July 2013 Published 20 December 2013
  • Correspondence: Manuel A. Franco, mafranco@javeriana.edu.co
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  • Abstract:

    Rotaviruses (RV) are ubiquitous, highly infectious, segmented double-stranded RNA genome viruses of importance in public health because of the severe acute gastroenteritis they cause in young children and many animal species. They are very well adapted to their host, with symptomatic and asymptomatic reinfections being virtually universal during the first 3 years of life. Antibodies are the major arm of the immune system responsible for protecting infants from RV reinfection. The relationship between the virus and the B cells (Bc) that produce these antibodies is complex and incompletely understood: most blood-circulating Bc that express RV-specific immunoglobulin (Ig) on their surface (RV-Ig) are naive Bc and recognize the intermediate capsid viral protein VP6 with low affinity. When compared to non-antigen-specific Bc, RV-Bc are enriched in CD27 memory Bc (mBc) that express IgM. The Ig genes used by naive RV-Bc are different than those expressed by RV-mBc, suggesting that the latter do not primarily develop from the former. Although RV predominantly infects mature villus enterocytes, an acute systemic viremia also occurs and RV-Bc can be thought of as belonging to either the intestinal or systemic immune compartments. Serotype-specific or heterotypic RV antibodies appear to mediate protection by multiple mechanisms, including intracellular and extracellular homotypic and heterotypic neutralization. Passive administration of RV-Ig can be used either prophylactically or therapeutically. A better understanding of the Bc response generated against RV will improve our capacity to identify improved correlates of protection for RV vaccines.

  • Citation: Franco M, Greenberg H. 2013. Rotavirus. Microbiol Spectrum 1(2):AID-0011-2013. doi:10.1128/microbiolspec.AID-0011-2013.

Key Concept Ranking

Immune Systems
Segmented Double-Stranded RNA
Peyer's Patches
Enzyme-Linked Immunospot Assay


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Image of FIGURE 1

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Flow cytometry experiment to characterize and compare RV-Bc to total Bc subsets (from reference 11 with modifications). Top row plots illustrate the Bc subsets considered. Middle row dot plots are gated on total CD20 Bc. Bottom row plots are gated on CD20 Bc that bind fluorescent RV VLPs (RV-Bc). As a first step in this analysis, Bc are evaluated for the expression of IgD and CD27 (left dot plots). IgD CD27 Bc are naive cells, and IgD CD27 (IgM, IgG, or IgA) are a low-frequency subset of mBc. The CD27 Bc of the left panels are further analyzed for the expression of IgD and IgM (right dot plots). IgM IgD cells are classical switched mBc; IgM IgD cells are called IgM-only mBc and resemble in many ways the switched mBc. IgD IgM cells are a poorly characterized subset of mBc. Double-positive IgM IgD mBc are a heterogeneous population of mBc; in the present experiment, they are further subdivided into IgM IgD (a phenotype that resembles marginal zone Bc) and IgM IgD. doi:10.1128/microbiolspec.AID-0011-2013.f1

Source: microbiolspec December 2013 vol. 1 no. 2 doi:10.1128/microbiolspec.AID-0011-2013
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Distribution of RV-Bc 9 months after primary oral infection of mice in selected organs (data from experiments reported in reference 25 ). The top panel shows numbers of IgG and IgA RV ASC per mouse, in different organs, evaluated by enzyme-linked immunospot assay. The middle panel shows numbers of RV-mBc (small IgD Bc) that bind RV VLPs per mouse, in different organs, evaluated by flow cytometry. The bottom panel shows the same data as the second panel but expressed as RV-mBc per 10 cells of the respective organ. LN, lymph node; LP, lamina propria. doi:10.1128/microbiolspec.AID-0011-2013.f2

Source: microbiolspec December 2013 vol. 1 no. 2 doi:10.1128/microbiolspec.AID-0011-2013
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Expression of the integrin α4β7 (the intestinal homing receptor) and CCR9 (chemokine receptor 9 whose ligand, TECK or CCL25, is selectively expressed in the small intestine) on RV-Bc (Bc that bind fluorescent RV VLPs) in children with acute (left dot plot)- or convalescent (right dot plot)-phase RV infection. The figure is from reference 14 , with modifications. doi:10.1128/microbiolspec.AID-0011-2013.f3

Source: microbiolspec December 2013 vol. 1 no. 2 doi:10.1128/microbiolspec.AID-0011-2013
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Blood-circulating Bc subsets in healthy adults and their enrichment or not in RV-Bc

Source: microbiolspec December 2013 vol. 1 no. 2 doi:10.1128/microbiolspec.AID-0011-2013

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