This work focused on immunohistochemistry markers of acute viral infections. Viral infected cells were detected by in situ based methods (reovirus, rabies virus) or cytologic changes (human papillomavirus, molloscum contagiosum virus, herpes simplex virus). Two proteins involved in nuclear trafficking, importin-β and exportin5, were detected in the infected cells for each virus and not in the control tissues. A wide variety of other proteins, including caspase-3, and bcl-2 family members (bcl2, bclX, MCL1, BAK, BAX, BIM, BAD) showed wide variations in expression among the different viral infections. Specificity of the importin-β and exportin-5 signals varied greatly with different commercially available peroxidase conjugates. It is concluded that immunohistochemistry detection of importin-β and exportin-5 may be useful markers of acute viral infection, which suggests that increased nuclear trafficking may be an important concomitant of viral proliferation.