Viral insecticides: Technological innovation, a new blue ocean of future pesticides

Viral Insecticides for Biological Control focuses on the basic as well as applied aspects of viral insecticides, which have the potential to significantly reduce the current reliance on chemical pesticide technology. Compared with traditional chemical insecticides, viral insecticides are highly targeted, environmentally friendly, and have been rapidly developed in the past few years, especially in organic agriculture. What is the current status of the development of viral pesticides, what new products and technologies are there, and how will they develop in the future. To this end, we interviewed several leading companies in virus pesticides. They are Cheng Qingquan, General Manager of Keyun Biotechnology, Philip Kessler,Director International Market Development of Andermatt Biocontrol, Chen Jiao, Wuhan Unioasis Biological Technology Co. Ltd.

Could you give a briefing of the development status and major applications of viral insecticide? 

Cheng Qingquan: At present, viral insecticide around the world is mainly used for control of cotton bollworm, soybean worm, spodoptera frugiperda, codling moth, prodenia litura as well as the resistant beet armyworm and plutella xylostella. Its market share has been growing constantly.

Kessler Philip: We are happy to recognize a general increase of biological plant protection tools in agriculture, particularly of microbial biocontrol technologies. Insect viruses, namely the baculoviruses, have been successfully applied for decades, as their high efficacy and safety has been recognized from early on. Several international biocontrol companies successfully develop and globally market products based on baculoviruses. There are also locally operating companies developing virus-based plant production products. However, the use of insect viruses compared to the overall microbial plant protection market is relatively low, since the use of each product is restricted to a single or relatively few numbers of target insects. If we estimate a yearly annual turnover of 70 m US$ for this product category, this represent only 3 % of the global microbial plant protection market. The market can surely accept many more insect virus products, as they are highly efficient, safe and compatible with many production strategies. The challenge lays in the high investment in registration for products to control single pest species, as it is clearly disproportionate to its market potential. As a consequence, there are very few virus species that have become global success stories like the insect viruses against Cydia pomonella (CpGV) and Helicoveropa armigera (HearNPV). Insect viruses are used in organic crops and conventional IPM strategies to manage MRL and resistance issues. So far virus insecticides find their way in strategies in high value crops such as pome fruit or citrus production, but since some years also in row crops such as cotton, sorghum or soybean. We also should not forget that some insect viruses have been very successfully applied to control important forest pests.

At present, more than 1,670 insect viruses have been discovered in more than 1,100 kinds of insects worldwide, which involve hosts of 43 families in 11 classes. In China, 291 kinds of insect viruses have been discovered. Although the research and development of viral insecticide started quite late, it has moved forward rapidly in recent years. There have been more than 60 kinds of viruses filed in various countries for registration which are now in the process of field trial while more than 30 kinds of viruses have been registered, produced and applied worldwide.

Chen Jia: Since 1993 when HaNPV wettable powder, the first viral insecticide, was granted registration in China, there have been 74 viral biopesticide products being granted registration by 2019, covering mother liquid and formulations. There are 26 HaNPV products, which accounts for the majority of the registrations. There are 12 insect virus varieties, eight of which are registered by Chuqiang Biotechnology, a wholly-owned subsidiary of Wuhan Unioasis Biological Technology. So far, more than 20 virus insecticide products have been registered in the United States, France, Switzerland, Russia, Brazil, Spain, Japan, South Africa, India and Australia. The main insect viruses used for biological control include NPV, PxGV and CPV, which are mainly used for control of plutella xylostella, beet armyworm, cotton bollworm and plusia agnata.

According to the outcome in the eighth report of the International Committee on the Taxonomy of Viruses in 2005, the recognized 5,000 virus species was split into 73 virus families, of which 230 species are insect viruses (definitely pathogenic to insect), being classified and included in the 18 virus families, including rhabdoviridae, roniviridae, biscistravirus, infectious PVA, ascoviridae, baculoviridae, birnaviridae, iridoviridae, metaviridae, nimaviridae, nodamura virus, orthomyxoviridae, parvoviridae, multicomponent virus, polyviridae, pseudoviridae, reoviridae and tetravirus. Insect viruses commonly used in crop control are mainly NPV and GV of baculoviridae, CPV of reoviridae. Viral insecticide has the superior properties of high safety, non-pollution, non-residue and non-resistance, having gradually attracted user’s attention.

Could you tell us about the status of research of viral insecticide (recombination of insect viruses or combined with small amount of chemical pesticide)? 

Cheng Qingquan: There are two kinds of recombination of viral insecticides. The first is the recombination between different insect viruses, including recombination of two or more different kinds of insect viruses. The purpose is to broaden product’s insecticidal spectrum via recombination, such that viral products can be accepted in more market applications. In the process of viral recombination, not only the insecticidal spectrum is expanded, but also some viruses are found to have a synergistic effect against other viruses, which improves the lethality of products and achievement of a better insecticidal effect.

On the other side, in order to improve the effect of control of insect virus on older larva, researches are made into recombination of insect viruses with some chemical pesticides. In this aspect, a breakthrough has been achieved. The method is, during the field spraying, to mix viral insecticidal products with some chemical pesticides for application as in a form of “combo” product. It is found upon application that some chemical pesticides have an obvious synergistic effect against insect viruses, which can speed up the death of insect pests infected with viruses, causing a higher death rate of insect pests. This has significantly increased user's acceptance of this kind of product due to its satisfactory control effect. 

In fact, in terms of chemical pesticides, especially some patented chemical pesticide products, the combined use of insect viruses with chemical pesticides to increase mutual synergy not only reduces the use of chemical pesticides, but also significantly reduces the resistance of insect pests to chemical pesticides, thus extending the product life cycle of chemical pesticides while pesticide residues are greatly reduced.

Chen Jiao: At present, there are two main virus mixture products on the market.

1.  Mixture with Bacillus thuringiensis (B.t)

Mixture products available on the market include EoNPV.Bt, SeNPV.Bt, AcNPV.Bt, HaNPV.Bt, PrGV.Bt and Bt.DCPV, being mostly the registrations of Wuhan Unioasis Biological Technology.

2. Mixture with low toxic or common chemicals (or alternative use) 

Mixture products available on the market include beta-cypermethrin.PINPV SC, phoxim.HaNPV and chlorfluazuron.PINPV SC.

The development trend of viral insecticide shows that the use of single agent is declining, formulation is speeding up, the market demand is growing strongly, NPV becomes dominant, especially the research of mixtures with AcNPV and PINPV, which are relatively more popular applications at present time.

The mixture of insect virus with chemical pesticide below lethal dose can also effectively enhance insecticidal rate, the reason may be that chemical pesticide below lethal dose cannot kill insect pest, but can greatly reduce the immunity of insect pest to increase the probability of infection, thus to achieve synergistic effect.

The purpose of mixture of insect virus with high-efficient and low-toxic chemical pesticide aims mainly to fix the fast-acting and long-lasting issue, reduce the amount of use of chemical pesticide, and gradually solve the problem of pesticide residues.

How much do you know about the insect virus infection-purposed synergetic substance? Can you share the knowledge and the major products on the insect virus infection-purposed synergetic substance?

Cheng Qingquan: The insect virus infection-purposed synergetic substance can destroy the normal physiological state of insect pest, thus lowering the immunocompetence of insect pest, increasing the chance of infection via viral penetration, and accelerating the extension of insect virus inside the insect pest. Hence, the lethality is increased and death rate of insect pest is increased. In particular, the control effect on older insect pests is very obvious.

Chen Jiao: In order to increase the efficiency of insect virus, action can be taken on insect’s infection mechanism and immunologic mechanism in combination with the characteristics of virus itself. Insect viruses mainly infect larva insect midgut tissue, there is a membranous tissue called peritrophin in insect’s midgut. The peritrophin is a reticular structure composed of chitin and protein, where the peritrophin including intestinal mucin and chitin binding protein, are tightly bound to the reticular structure, whilst polysaccharides are filled up in the interspace of the reticular structure to form a semi-permeable membrane with certain pore size. Some factors, which would affect peritrophin, can increase the viral infectivity of pathogenic microorganisms, especially NPV to the insects via interference with the normal formation of peritrophin or by destructing its integrity. In 1959, Tanada reported for the first time the synergism of two kinds of mixed baculoviruses to infect the same host. At present, the ways of synergism include biological synergism and chemical synergism.

1. Biological Synergism 

The active substance of biological synergism is the virus enhancer, which used to be called synergistic factor, viral enhancing factor or enhancing protein. Today it is given a unified name - enhancer, being the recombination of synergistic protein and enzyme as well as baculovirus. There are totally 11 kinds of synergistic proteins, including 2 kinds of EPV, 5 kinds of GV, 2 kinds of NPV and 2 kinds of CPV (data as of 2005). What are included in documentation include baculovirus enhancin, poxvirus fusolin, baculovirus GP37 protein; the use of GV and NPV together is also synergistic. GV enhancer, as a proteolytic enzyme which destructs peritrophin, can increase the pore size of peritrophin and the permeability into NPV. Enzyme synergistic factors include chitinase which is hydrolytically specific to insect chitin and the cathepsin. Baculovirus recombination is a genetic baculovirus recombination to expand its insecticidal spectrum.

Bacillus thuringiensis (B.T) can be mixed with NPV. Compared with insect virus, B.t has low cost and fast effect. When being mixed with insect virus, the insecticidal effect is obviously much improved. This kind of synergism is represented by the registrations of Wuhan Unioasis Biological Technology including EoNPV.B.t SC, HaNPV SC and AcNPV.B.t SC.

2. Chemical Synergistic factors 

Insect growth regulator: chitin synthesized inhibitors (chlorfluazuron, etc.) can inhibit chitin synthesis after insect uptake, thus affecting the structure of peritrophin and accelerating the viral infection on insects. UV protectant: folic acid, ascorbic acid, 2-phenylbenzimidazole-5-sulfonic acid, Congo red, brilliant yellow and acridine yellow. The fluorescent whitening agent OB is synergistic on AcMNPV.

1) Fluorescent whitening agent, according to researches, not only protects insect virus from UV radiation but also enhances NPV infection on hosts. There are few studies made on the synergistic mechanism of fluorescent whitening agent on virus, the research is mostly concentrated on insect midgut.

2) Chemical synergists, such as the added food attractant, can stimulate food uptake, which increases the amount of ingested virus, thus enhancing the insecticidal activity.

What do you think to be the main advantages of viral insecticides? Why? 

Cheng Qingquan: The main advantages of viral insecticides are: (1) targeted insect pest, acting only for control of target insect pest, without hurt to non-target organism such as natural enemies, which is conducive to maintaining an ecological balance and prevent repeated pest-outbreak; (2) insect pest is not apt to be resistant, as insect virus is essentially a kind of microorganism of nucleic acid structure, which can co-evolve with insect pest while the latter has difficulty in producing resistance. Therefore, compared with chemical pesticides, viral insecticides would have more market potentials in respect of resistance management; (3) being safe without residues, as the main components of viral insecticide are natural organisms, and there is no safety interval requirement on the product. Therefore, crops can be harvested on the same day as applications are conducted. As for organic production and green agricultural production, which have residue requirement, viral insecticides are regarded as a green pest control product, which can be used at ease. 

Kessler Philip: Thanks to their specificity, the different baculovirus species are harmless for non-target insects and arthropods. This highly specific use of baculoviruses only controls the target pest insects ensuring there is no effect on non-targets. Therefore, protecting the existing beneficial fauna that can be important to supress outbreaks of secondary pest species. This significantly reduces the overall input of insecticides also against other pests. Baculoviruses have a unique mode of action. The viruses infect and multiply within the insect larvae causing death, the virus can then be transferred to following pest generations and result in a sustainable population reduction of the pest population. Its unique mode of action has the further advantage to address resistance towards other insecticides, or to manage resistance prevention in pest control strategies. The existing virus formulations are easy to use and can be sprayed as any other insecticide. They are compatible with mostly all other active ingredients. We see therefore growing potential to use insect viruses in combined strategies within integrated pest management systems.

Chen Jiao: Compared with other pesticides, viral insecticides have the following advantages:

1. Specificity: the infection mechanism of insect virus requires identification and combination of the cell surface receptor glycoprotein of the host cell via the spike protein on the virus surface, only in this way can the host be infected and only the target host is killed.

2. Higher safety: it is harmless to human and livestock, it does not kill natural enemies and other beneficial insects, does not pollute the environment, and is of great help to protection of the ecological chain.

3. Non-residue: a virus is a protein, without residue on crops.

4. Epidemic: virus can spread horizontally and vertically in pest population, being infectious.

5. The production process is pollution-free and low energy consuming. An insect is a virus synthesis factory.

6. High efficient and long lasting: NPV can remain active in the soil for as long as 5 years. After death, dead and decayed insect bodies will release a large number of viruses in the field, which maintains the viral quantity in the field, hence the number of pesticide application is reduced, and the cost of application and labor is reduced, resulting accordingly in a decreased comprehensive cost.

7. Resistance will not occur easily: virus does not have cell structure and complete enzyme system, the factors which act on metabolic pathways are not affected, and thus resistance will not occur easily. So far, there are has been no report of occurrence of resistance to insect virus. An example is that the human body is not resistant to novel coronavirus and SARS, also without relevant immunity, and no specific medications are available.

We understand that the instability and poor lasting effect of viral insecticides have always been a problem which restricts the promotion of the use of viral insecticides. What do you think of the problem and how would you propose to solve the problem? Do you have any latest products and technologies that can make up for the situation?

Cheng Qingquan: The instability and poor lasting effect are attributed to the reduced activity of the virion under the adverse environmental conditions such as ultraviolet irradiation and high temperature. With regard to this situation, there are solutions in two ways. One way is to add protective agent such as UV protectant to prevent ultraviolet irradiation, so as to improve product performance and property. The other way is to take measures accordingly during the filed application such as the use of insect sex attractant to determine the time of insect infestation, so as to accurately conduct applications. Moreover, pesticide application can be conducted to the greatest extent in cloudy days or evening, such that viruses can play a better role in achieving its best control effect.

Kessler Philip: Viruses can sustainably suppress population in the long term. However, a reduced stability in the field has often been used as an argument against the use of virus products. It was perceived that the main challenge was the reduced viability of virus particles when exposed to UV radiation.  However, insect viruses are no less stable towards UV radiation than most other microorganisms and as an industry we have learned to address these challenges. Advanced knowledge in the production and formulation of insect viruses has increased the resilience of virus particles which results in increased stability and viability after application. Therefore, as an R&D focused company, we not only concentrate on the development of new active ingredients but also on the improvement of production processes and development of stable formulations.  A further key success is the understanding of host-pathogen relationship, where we have learned how to adjust the application of insect viruses in the field to the biology and development of the host. To maximise success, it is crucial to recognize optimal application timings and to avoid unsuitable conditions after application. This can seem quite complicated, so we invest much time with simple training tools that provide robust recommendations for the farmers.  So in conclusion, the progress we have made in stability and sustainability is not only the development of improved product quality and formulations, but also the development of suitable and reasonable application strategies in the field that achieve the best results to gain customers satisfaction.

Chen Jiao: Due to the simple biological structure of insect virus, its tolerance to high temperature and ultraviolet is poor, and it may lose activity in the field. However, the long lasting effect is a major advantage of insect virus, which is not a problem for product promotion, especially after the continuous use of insect virus, the population density of insect pest in the field are greatly reduced. In the later period, the amount of use and the number of applications will continue to decrease year by year.

The issue of instability of viral insecticide in the field can be solved via two approaches:

1. To strengthen the development of viral insecticide formulations

First of all, an anti-UV adjuvant can be added to solve the problem of ultraviolet radiation; some adjuvants to increase adhesion can be added to protect the long lasting effect of insect virus. On the other hand, the retention of the formulations in the field and the stomach toxicity may need to be increased.

Secondly, it can be mixed with B.t to solve the problem of unstable viral activity under different temperature conditions. The viral products registered by the company are mainly mixtures with B.t.

2. To have a prediction and forecast technique to grasp the right timing of viral insecticide application, thus to solve farmer’s problem existing on the timing of applications.

First of all, from ecological perspective, the national policy is changing, where the concept of “pest control with decreased amount of pesticide” is put forward, which is also an opportunity for viral insecticide products. We ought to change our business thinking to fully realize the series of problems caused by chemical pesticide to the natural environment and the threat of pesticide residues to human health. In the meantime, we need to realize that the insect pest management is not just a random fight based on excessive use of pesticide to achieve immediate result for a moment’s comfort, which may cause abused use of chemical pesticide, leading to extermination and extinction of insect pest.

Secondly, in order to fix the issue of instability, the products need to be used in conjunction with the insect population forecast system (insect pest forecast in advance), so as to grasp the right timing of application, which will change farmer’s mistake of “applying pesticide when seeing pest". Because of the special characteristics of viral insecticide, the best time to get pest infected is the peak time of egg hatching and instar 1 - 2, when larvae are at low immunity, which is the period when insect pest is easily infected by virus. Therefore, the application on the right time can improve the insecticidal stability.

Finally, we will strengthen our research and development, and will launch a series of full course solutions via multiple pilot schemes which will constantly optimize our products. Meanwhile, we will strengthen promotion of correct use of viral insecticidal products to gradually narrow the gap between viral insecticide and the common chemical pesticide on the market in terms of pest control effect, especially to solve the problem of chemical pesticide residues via the use of viral insecticide for pest control during crop harvesting. In this way, the benefit to ecology, environment and human health is achieved while pest is controlled.

What are the main viral insecticides available from your company?

Cheng Qingquan: At present, we manufacture products in technical material and formulation which contain cotton bollworm nucleopolyhedrosis virus, beet armyworm nucleopolyhedrosis virus, prodenia litura nucleopolyhedrosis virus, spodoptera frugiperda nucleopolyhedrosis virus, autographa californica nucleopolyhedrosis virus, cabbage moth nucleopolyhedrosis virus and plutella xylostella granulosis virus.

Kessler Philip: Andermatt Biocontrol is proud to develop and offer a large range of different insect viruses in the past 30 years. Our products are now used in a broad range of different crops worldwide. Our subsidiaries Andermatt Biocontrol Suisse and Sylvar Technologies are manufacturing the virus products in Switzerland and in Canada respectively. Initial growth came from the development of Cydia pomonella granulovirus (MADEX) and Adoxophyes orana granulovirus (CAPEX) to control codling moth and summer fruit tortrix respectively, two key pest insects in pome fruit production. Over the years we significantly enlarged our portfolio of Cydia pomonella granulovirus products and pioneered the development of new products based on CpGV to control resistant codling moth population (MADEX PLUS, MADEX MAX, MADEX TOP) or to increase its efficacy against oriental fruit moth (MADEX TWIN). We produce and sell a Cryptophlebia leucotreta granulovirus (CRYPTEX) which has become a standard tool in false codling moth control in Southern Africa. Furthermore, Andermatt Biocontrol Suisse and Sylvar Technologies produce nucleopolyhedroviruses against global pest insects such as Helicoverpa sp., Spodoptera exigua, Spodoptera littorals, Spodoptera frugiperda, Chrysodeixis includens and Trichoplusia ni (HELICOVEX. SPEXIT, LITTOVIR, SPODOVIR, LOOPOVIR, LOOPEX). In addition, Sylvar has successfully engineered virus products to be used against the forest pest insects such as balsam fir sawfly and gypsy moth (ABIETIV, DISPARVIRUS). Our latest success story is TUTAVIR, a baculovirus to control Tuta absoluta, a globally significant tomato pest insect. This new product fills an important gap in existing control strategies against Tuta absoluta, as many other available insecticides show reduced efficacy against this pest. For the development of TUTAVIR, Andermatt Biocontrol has been granted the Bernard Blum Award 2019. Our efforts will not only be focussing on the marketing of single species solutions, but also on addressing the challenges of farmers with pest complexes in various crops. Mixture of viruses and the combination with other active ingredients can offer further flexibilities and options for farmers. The use of insect virus products definitively contributes to a healthier and sustainable food production.

Chen Jiao: At present, our company mainly produces the following products:

This report was originally published in AgroPages' 2020 Biologicals Special. 

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