Rotavirus: to the gut and beyond!

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Abstract
Rotavirus causes severe gastroenteritis in children. A principle of rotavirus pathogenesis has been that the infection remains localized to epithelial cells in the small intestine. This dogma was challenged by recent findings of rotavirus in the serum of experimentally infected animals and children with diarrhea. Repeated associations of rotavirus infections with a wide range of nongastroenteric clinical manifestations in humans were considered spurious because of lack of proof that rotavirus escaped the intestine. New data outlined in this review, however, show that rotavirus routinely infects systemically and highlight controversies and future research questions. Rotavirus antigens (antigenemia), RNA, or infectious virus (viremia) has been demonstrated in the serum and many extraintestinal tissues in all experimental animal models. Rotavirus antigens and RNA have been detected in the sera of children with rotavirus diarrhea. The tissues and cell types that support rotavirus replication outside the intestine and the consequences of extraintestinal reservoirs of infection are beginning to be examined. Rotavirus infection is systemic, with an acute active viremia and extraintestinal replication. The impact of systemic rotavirus on disease burden remains to be determined.