The human polyomavirus, JCV, uses serotonin receptors to infect cells

The human polyomavirus, JCV, causes the fatal demyelinating disease progressive multifocal leukoencephalopathy in immunocompromised patients. We found that the serotonergic receptor 5HT2AR could act as the cellular receptor for JCV on human glial cells. The 5HT2Areceptor antagonists inhibited JCV infection, and monoclonal antibodies directed at 5HT2Areceptors blocked infection of glial cells by JCV, but not by SV40. Transfection of 5HT2Areceptor–negative HeLa cells with a 5HT2A receptor rescued virus infection, and this infection was blocked by antibody to the 5HT2A receptor. A tagged 5HT2A receptor colocalized with labeled JCV in an endosomal compartment following internalization. Serotonin receptor antagonists may thus be useful in the treatment of progressive multifocal leukoencephalopathy

Recombinant human activated protein C inhibits integrin-mediated neutrophil migration

Integrin-mediated cell migration is central to many biologic and pathologic processes. During inflammation, tissue injury results from excessive infiltration and sequestration of activated leukocytes. Recombinant human activated protein C (rhAPC) has been shown to protect patients with severe sepsis, although the mechanism underlying this protective effect remains unclear. Here, we show that rhAPC directly binds to β1 and β3 integrins and inhibits neutrophil migration, both in vitro and in vivo. We found that human APC possesses an Arg-Gly-Asp (RGD) sequence, which is critical for the inhibition. Mutation of this sequence abolished both integrin binding and inhibition of neutrophil migration. In addition, treatment of septic mice with a RGD peptide recapitulated the beneficial effects of rhAPC on survival. Thus, we conclude that leukocyte integrins are novel cellular receptors for rhAPC and the interaction decreases neutrophil recruitment into tissues, providing a potential mechanism by which rhAPC may protect against sepsis