Trichosanthin (TCS) is a type I ribosome-inactivating protein that inhibits the replication of both human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 1 (HSV-1) The mechanism of inhibition is not clear This investigation explored the effects of TCS on the stages of HSV-1 infection in Hep-2 cells from attachment to release We demonstrated that TCS reduced HSV-1 antigen and DNA content and interfered with viral replication as early as 3-15 h after infection TCS had no effect on HSV-1 attachment penetration or immediate-early gene expression However the expression of early and late genes and virion release were diminished In summary this study demonstrates that TCS primarily affects HSV-1 replication in Hep-2 cells during the early to late infection period (C) 2010 Elsevier Inc All rights reserved