Inhibition of melanization activation by Serpin-5 and Serpin-9 promotes nucleopolyhedrovirus infection in cotton bollworm Helicoverpa armigera

One of important insect defense mechanisms is melanization, which are mediated by clip domain serine protease (cSP) cascades and regulated by Serpins. In vitro, activation of melanization can efficiently kill Nucleopolyhedrovirus (NPV). However, quantitative proteomics revealed that the infection of NPV in cotton bollworm Helicoverpa armigera suppressed protein levels of melanization components in the host hemolymph. It also reduced the prophenoloxidase (PPO) activity. In contrast, Serpin-9 and -5 were sequentially up-regulated. Serpin-5 and -9 induced by NPV infection play important roles in regulate host melanization by directly inhibiting their target proteases cSP4 and cSP6 respectively. Furthermore, Serpin-5 or -9 depleted insects exhibited high PO activities and show resistance to NPV infection. Together, our results characterized melanization cascade in H. armigera, and suggests that natural insect virus NPV has evolved a distinct strategy to suppress host immune system. This finding may be exploited to design more potent viruses against agricultural pests.