Antagonism to human BST-2/tetherin by Sendai virus glycoproteins

Tetherin is an interferon-inducible factor that restricts viral particle production. We show here that Sendai virus (SeV) induces a drastic decrease in tetherin levels in infected HeLa cells. Using ectopic expression of tetherin in Madin-Darby canine kidney cells, we find that infectious SeV production is sensitive to restriction by tetherin, suggesting that SeV downregulates tetherin to counter this form of cellular restriction. By using radioactive tetherin in pulse-chase experiments, applying conditions that limit protein degradation, and by estimating tetherin mRNA levels, we find that tetherin degradation is the mechanism of downregulation. Suppression of the virus envelope proteins matrix, fusion (F) or haemagglutinin-neuraminidase protein (HN) during the course of infection demonstrates that F and HN, in concert, are responsible for tetherin degradation. The mechanism(s) by which these two viral glycoproteins participate in degrading tetherin remains to be determined.