How Neonicotinoids Promote Deformed Wing Virus And Impair Immunity In Honey Bees

This is a summary of an important scientific study by Di Prisco et al examining how low doses of neonicotinoids impair immunity to diseases and viruses such as DWV, in honey bees:

"Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees."

Di Prisco G, Cavaliere V, Annoscia D, et al. Proc Natl Acad Sci U S A. 2013;110(46):18466-71. (Ref 1).

Key Points

  • Honey bees are exposed to a range of stress factors, which acting together, may cause honey bee colony losses that are often associated with a high level of infectious micro-organisms that cause disease (pathogens).
  • Neonicotinoid insecticides have been reported to enhance the impact of pathogens, although how the immune system is altered to enable this to happen, is unclear.
  • In this study, the scientists identify and describe the molecular mechanism (the way) through which the neonicotinoid clothianidin impedes the insect immune response, thus enabling viral pathogens to multiply in honey bees that have a covert infection.

    (A covert infection is one that is present, but not showing symptoms or hampering the host in any way, such that it is not noticeable and the host can function as normal).


But wait!

"If the disease is already in a creature's body, surely it's only a matter of time before they begin to show signs of disease, and possibly die?"

Answer:

Actually, no, this is not correct.  All creatures can carry diseases, viruses and bacteria that have the potential to cause real harm and even death, and yet the symptoms of the disease never become apparent.

Here is a comment from a paper published by the esteemed biological research journal, The Royal Society Publishing:

"it is estimated that one-third of the human population is infected with Mycobacterium tuberculosis (Dye et al. 1999); however, only 5–10% of these infections cause overt disease within the first 2 years. Many individuals that have a covert infection will never express the overt, active TB infection that causes disease and has the potential for horizontal transmission (WHO Report 2005)." 

(Ref 2).

Important Background 

In order to understand this paper, a little simplified background information is worth including, so here goes.

Important Proteins

The bodies of insects produce a number of different protein molecules, each performing its own important role.  Protein molecules are receptors, meaning they receive and respond to signals and/or stresses outside the cell itself.

One protein complex called NF-kB is very important for causing immune responses to stresses, such as harmful bacteria and viruses.  In other words, this protein is a receptor that responds to harmful bacteria and viruses, so it is very important for the insect’s ability to fight off diseases.  

Nevertheless, if an insect’s response is too sensitive to stressors, then this is actually harmful to the insect – it could actually over-react to beneficial gut (stomach) bacteria that the insect needs to keep it healthy.  So, to keep the amount of NF-kB receptors in check, the insect’s body produces another protein, called LRR (which stands for Lutein Rich Repeat). 

However, if the insect has too many LRR receptors, then it will over-regulate the amount of NF-kB in the insect’s body, such that it cannot produce enough NF-kB to fight off diseases and viruses that are harmful.

So you can see that insects (including honey bees) need the correct balance of these 2 proteins in order to have a healthy immune system that fights off diseases and viruses whilst allowing beneficial gut bacteria to thrive:

  • one called NF-kB, and another called LRR.


Experiment Results


So what did the scientists find when honey bees were exposed to a sub-lethal dose of the neonicotinoid clothianidin? 

(Note: A sub-lethal dose is an amount that will not immediately cause death.  However, sub-lethal doses can have subtle effects that ultimately harm and eventually cause death).

Summary

The scientists found that exposure to the neonicotinoid clothianidin resulted in an imbalance of the 2 important proteins so that: 

  • The bee has too many LRR receptors, resulting in a negative impact on NF-kB – the protein responsible for immune responses to pathogens.  
  • The honey bee’s anti-viral defences are therefore impaired so that the bee is now vulnerable to multiplication of viruses and disease.
  • In the study, this resulted in a multiplication of Deformed Wing Virus (DWV) infection in the honey bees, where previously only a covert infection of the virus had been present.

  • The scientists also performed this experiment with the organophosphate chlorpyriphos, and found that the chemical had no significant impact on the proteins.
  • The scientists fed the honey bees with sub-lethal doses of neonicotinoid to match concentrations and contamination levels that would match field conditions, ranging from 0.1 to 10 ppb (parts per billion).  Interestingly, they found that neonicotinoids (clothianidin and imidacloprid) were active in promoting the multiplication and proliferation of Deformed Wing virus.  The scientists make the point that infections were induced in a similar way (immunosuppression) by the neonicotinoid imidacloprid.

Conclusions

  • In causing viruses to multiply, the subtle effects of very low-dose neonicotinoids, might also be negative in the natural environment.
  • Covert infection of DWV is an extremely frequent occurrence in a large number of apiaries all over the world.  Given this fact, the scientists state that using their proposed honey bee stress models, it is possible to predict that neonicotinoids may promote the proliferation of DWV in bees bearing covert infections.  

Quote:

"The occurrence at sublethal doses of this insecticide-induced viral proliferation suggests that the studied neonicotinoids might have a negative effect at the field level."

Other Observations

In the paper, the scientists refer to a number of other studies, worthy of mention here, considering their potential impact on proteins that play an important part in immunity:

  • Mediterranean Mussel
    Ecotoxicological studies have reported that exposure of Mytilusg    allo provincialis (meditaerranean mussel) to sublethal doses of the neonicotinoid insecticide thiacloprid affects proteins important for immune function. 
  • Common Fruit Fly
    In this experiment concerning the larvae of the common fruit fly, Drosophila melanogaster, scientists were interested in what would happen to the levels of the protein NF-kB (the one responsible for immune responses) when exposed to standard dose LD50) of clothianidin. 

They found that the percentage of fruit fly larvae showing an intense response to immune challenge, was significantly lower in larvae exposed to clothianidin, than in the control group. 

In other words, larvae that had been exposed to the neonicotinoid, were not producing so much of the protein NF-kB, which is important for fighting diseases and pathogens.

Again, no such impact on the disease fighting protein was exhibited when the larvae were exposed to the organophosphate chlorpyriphos.


Comments

  • This is yet another scientific paper highlighting the dangers of neonicotinoids to invertebrates.  
  • Neonicotinoids are also implicated in the proliferation of nosema in bees.
  • Potentially, neonicotinoids could hamper the ability of bees to deal with Varroa mite.
  • The studies on mussels and fruit flies may highlight the dangers of neonicotinoids to other invertebrates including thosse in aquatic environments. 

References

1. Di Prisco G, Cavaliere V, Annoscia D, et al. "Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees."  Proc Natl Acad Sci U S A. 2013;110(46):18466-71.

2. The evolution of covert, silent infection as a parasite strategy Ian Sorrell , Andrew White , Amy B. Pedersen , Rosemary S. Hails , and Mike Boots .  Published:11 March