MxA is an interferon-induced antiviral protein. Viral replication relies on the trafficking machinery of the host cell. Overexpression of MxA was found to perturb trafficking of internalized transferrin resulting in its accumulation in cells. Interestingly, this perturbation of endocytic trafficking was transient-with a maximal effect being seen 5-6 h after transfection. By 12 h after transfection the perturbation of endocytosis was seen to have subsided although MxA protein levels remained elevated even 24 h after transfection. The accumulation of transferrin is due to a block in transferrin recycling. It is further shown that MxA can physically associate with the endocytic protein dynamin, possibly accounting for the observed effect of MxA expression on transferrin endocytosis, These results uncover a hitherto unknown aspect of MxA action on trafficking processes within cells. (C) 2004 Elsevier Inc. All rights reserved.