Identification of a role for nucleolin in rabies virus infection.

Rabies virus replicates in the cytoplasm of host cells, but rabies virus phosphoprotein (P-protein) undergoes active nucleocytoplasmic trafficking. Here we show that the largely nuclear P-protein isoform P3 can localize to nucleoli and forms specific interactions with nucleolin. Importantly, depletion of nucleolin expression inhibits viral protein expression and infectious virus production by infected cells. This provides the first evidence that lyssaviruses interact with nucleolin and that nucleolin is important to lyssavirus infection.

Conservation of a unique mechanism of immune evasion across the Lyssavirus genus.

The evasion of host innate immunity by Rabies virus, the prototype of the genus Lyssavirus, depends on a unique mechanism of selective targeting of interferon-activated STAT proteins by the viral phosphoprotein (P-protein). However, the immune evasion strategies of other lyssaviruses, including several lethal human pathogens, are unresolved. Here, we show that this mechanism is conserved between the most distantly related members of the genus, providing important insights into the pathogenesis and potential therapeutic targeting of lyssaviruses.

Tetraspanin microdomains in immune cell signalling and malignant disease.

A contemporary goal of researchers in leucocyte signalling has been to uncover how cells physically organize and compartmentalize signalling molecules into efficient, regulated signalling networks. This work has revealed important roles of membrane microdomains that are characterized by their distinctive protein and lipid compositions. Recent studies have demonstrated that besides typical cholesterol- and glycosphingolipid-enriched 'rafts', leucocyte membranes are equipped with a different type of microdomain, made up of tetraspanin proteins. Tetraspanin proteins are involved in the organization of tetraspanin-enriched microdomains by virtue of their capacity to specifically associate with key molecules, including integrins, leucocyte receptors and signalling proteins. The aspects of leucocyte function influenced by tetraspanin microdomains include adhesion, proliferation and antigen presentation. However, the mechanisms by which tetraspanin complexes link to intracellular signalling pathways, are still largely unknown. This review discusses how tetraspanin microdomains might function to regulate signalling in lymphoid and myeloid cells, and how they relate to lipid rafts. In addition, we discuss new insights into the role of tetraspanins in malignant disease.