Mechanisms of reovirus bloodstream dissemination.

Boehme KW, Lai CM, Dermody TS
Adv Virus Res. 2013 87: 1-35

PMID: 23809919 · PMCID: PMC4603565 · DOI:10.1016/B978-0-12-407698-3.00001-6

Many viruses cause disease within an infected host after spread from an initial portal of entry to sites of secondary replication. Viruses can disseminate via the bloodstream or through nerves. Mammalian orthoreoviruses (reoviruses) are neurotropic viruses that use both bloodborne and neural pathways to spread systemically within their hosts to cause disease. Using a robust mouse model and a dynamic reverse genetics system, we have identified a viral receptor and a viral nonstructural protein that are essential for hematogenous reovirus dissemination. Junctional adhesion molecule-A (JAM-A) is a member of the immunoglobulin superfamily expressed in tight junctions and on hematopoietic cells that serves as a receptor for all reovirus serotypes. Expression of JAM-A is required for infection of endothelial cells and development of viremia in mice, suggesting that release of virus into the bloodstream from infected endothelial cells requires JAM-A. Nonstructural protein σ1s is implicated in cell cycle arrest and apoptosis in reovirus-infected cells but is completely dispensable for reovirus replication in cultured cells. Surprisingly, a recombinant σ1s-null reovirus strain fails to spread hematogenously in infected mice, suggesting that σ1s facilitates apoptosis of reovirus-infected intestinal epithelial cells. It is possible that apoptotic bodies formed as a consequence of σ1s expression lead to reovirus uptake by dendritic cells for subsequent delivery to the mesenteric lymph node and the blood. Thus, both host and viral factors are required for efficient hematogenous dissemination of reovirus. Understanding mechanisms of reovirus bloodborne spread may shed light on how microbial pathogens invade the bloodstream to disseminate and cause disease in infected hosts.

Copyright © 2013 Elsevier Inc. All rights reserved.

MeSH Terms (17)

Animals Apoptosis Capsid Proteins Cell Adhesion Molecules Cell Cycle Checkpoints Humans Intestinal Mucosa Intestines Lung Mice Receptors, Cell Surface Receptors, Virus Reoviridae Reoviridae Infections Respiratory Mucosa Viremia Virus Replication

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