Dissection of two modes of IE1 sub-nuclear localization in baculovirus-infected cells

• We screened a chemical library with a recombinant baculovirus.
• An inhibitor of baculovirus-IE1 focus formation, dBIQdO, was identified.
• dBIQdO reduces viral titers following infection at a low MOI.
• dBIQdO revealed that IE1 foci are not essential for virogenic-stroma formation.

Prior to viral DNA replication, baculovirus IE1 exhibits a focal distribution within the cell nucleus. During DNA replication, the IE1 foci apparently expand and develop into a virus replication center called the virogenic stroma (VS). In our search for chemical compounds capable of modulating Bombyx mori nucleopolyhedrovirus (BmNPV: a prototype of baculovirus) replication, we found an inhibitor (dBIQdO) of IE1 focus formation. VS formation, however, was not affected, suggesting that IE1 foci are not essential for VS formation and that IE1 possesses two independent mechanisms for sub-nuclear localization. In addition to inhibition of IE1 focus formation, dBIQdO also reduced viral titers following infection at a low MOI. Comparison of the effects of three chemicals, dBIQdO, aphidicolin and caffeine, on IE1 localization allowed us to detect a shift from focal distribution to VS localization, suggesting that IE1 foci are disassembled prior to VS formation.