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Natural Insect Virus Baculovirus has Evolved a Distinct Strategy to Suppress the Host Immune System

Dec 15, 2017     Email"> PrintText Size

Melanization is one of important modules in insect defense system. It consists of a cascade of clip-domain serine proteases (cSPs) that converts the zymogen prophenoloxidase (PPO) to active phenoloxidase (PO), which is negatively regulated by serpins. PO then catalyses the formation of melanin that physically encapsulates certain pathogens.

Parasites and bacteria have evolved to produce specific proteins or antibiotic to suppress the melanization response of host insects for survival. However, the mechanisms by which virus persists in the face of the insect melanization are poorly understood. 

In a present study by cooperation with research group led by Prof. ZOU Zhen in Institute of Zoology of the Chinese Academy of Sciences, the research group led by Prof. HU Zhihong in Wuhan Institute of Virology showed that a DNA virus baculovirus infection of the cotton bollworm, Helicoverpa armigera, reduced the levels of most cascade members in the host hemolymph and PO activity. 

By contrast, serpin-9 and serpin-5 were sequentially upregulated after the viral infection. Their results also revealed that melanization kills baculovirus in vitro.

Serpin-5 and serpin-9 regulate melanization by directly inhibiting their target proteases cSP4 and cSP6, respectively and cSP6 activates PPO purified from hemolymph. Moreover, serpin-5/9-depleted insects showed resistance to baculovirus infection.  

In summary, their findings have enriched the understanding of molecular mechanisms by which pathogens suppress the melanization response of host insect for survival. The scientists envision a mechanism whereby baculovirus overcomes host melanization.

The viral infection induces the level of serpin-5 and serpin-9 in hemolymph. Serpin-5 specifically inhibits cSP4, and serpin-9 inhibits cSP6 and cSP29, resulting in a dramatic decline of PO activity to suppress the virucidal capacity of host melanization.  

This mechanism, which involves baculovirus induced serpin-5 and serpin-9 and then inactivates the host immune system, suggests that these two negative regulators of immune response are important for baculovirus infection in insects. These findings improve our understanding of the interaction between HearNPV and its co-evolutionary host H. armigera.  

The results have been published in PLoS Pathogens entitled "Inhibition of melanization by serpin-5 and serpin-9 promotes baculovirus infection in cotton bollworm Helicoverpa armigera".  

This work was supported by grants from Strategic Priority Research Program of the Chinese Academy of Science, National Key Plan for Scientific Research and Development of China, National Natural Science Foundation of China, Key research project of frontier science of Chinese Academy of Sciences, and Open Research Fund Program of State Key Laboratory of Integrated Pest Management.

 

Proposed model for regulation of PPO activation cascade in H. armigera during baculovirus infection. (Image by HU Zhihong) 

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(Editor: ZHANG Nannan)

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HU Zhihong

Wuhan Institute of Virology

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E-mail: huzh@wh.iov.cn

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