Rotavirus

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.

Differential Expression of IgM and IgD Discriminates Two Subpopulations of Human Circulating IgM+IgD+CD27+ B Cells That Differ Phenotypically, Functionally, and Genetically

“…We have confirmed here that RV-B cells are particularly enriched in the IgM hi vs. the IgM lo B cells ( Supplementary Figures 1A-C). While the IGHV1 family is the dominant family used by naïve RV-B cells, the IGHV3 family is dominant in both IgM and class-switched RV-Bmem cells (5,61), which is in agreement with the significant decrease and increase we found in the respective use of IGHV1 and IGHV3 families by IgM hi B cells relative to naïve B cells ( Figure 4A). Since RV replicates in the intestine and given the recent proposal that intestinal MZB cells diversify their Ig repertoire in GALT to later travel, via the blood, to the spleen to fulfill their function (24), it is tempting to speculate that RV selects a subset of IgM hi B cells in the intestine.…”

Multiple Introductions and Antigenic Mismatch with Vaccines May Contribute to Increased Predominance of G12P[8] Rotaviruses in the United States

“…Limited antibody responses to VP4 after vaccination may result in little selective pressure, whereas highly cross-reactive VP7-specific antibodies may negatively select for rotaviruses with homologous VP7 proteins and positively select for antigenic drift and rotaviruses with the most divergent VP7 proteins. However, clear correlates of protection for rotavirus following vaccination have not been well established (19,(68)(69)(70)(71). While protection following vaccination mostly correlates with levels of rotavirus-specific antibodies, the roles of neutralizing antibodies and other factors in mediating protection are less clear, particularly in children.…”