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Synergistic parasite-pathogen interactions mediated by host immunity can drive the collapse of honeybee colonies.

Nazzi F, Brown SP, Annoscia D, Del Piccolo F, Di Prisco G, Varricchio P, Della Vedova G, Cattonaro F, Caprio E, Pennacchio F - PLoS Pathog. (2012)

Bottom Line: The de-stabilisation of DWV infection is associated with an immunosuppression syndrome, characterized by a strong down-regulation of the transcription factor NF-κB.The centrality of NF-κB in host responses to a range of environmental challenges suggests that this transcription factor can act as a common currency underlying colony collapse that may be triggered by different causes.Our results offer an integrated account for the multifactorial origin of honeybee losses and a new framework for assessing, and possibly mitigating, the impact of environmental challenges on honeybee health.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Scienze Agrarie e Ambientali, Università degli Studi di Udine, Udine, Italy. francesco.nazzi@uniud.it

ABSTRACT
The health of the honeybee and, indirectly, global crop production are threatened by several biotic and abiotic factors, which play a poorly defined role in the induction of widespread colony losses. Recent descriptive studies suggest that colony losses are often related to the interaction between pathogens and other stress factors, including parasites. Through an integrated analysis of the population and molecular changes associated with the collapse of honeybee colonies infested by the parasitic mite Varroa destructor, we show that this parasite can de-stabilise the within-host dynamics of Deformed wing virus (DWV), transforming a cryptic and vertically transmitted virus into a rapidly replicating killer, which attains lethal levels late in the season. The de-stabilisation of DWV infection is associated with an immunosuppression syndrome, characterized by a strong down-regulation of the transcription factor NF-κB. The centrality of NF-κB in host responses to a range of environmental challenges suggests that this transcription factor can act as a common currency underlying colony collapse that may be triggered by different causes. Our results offer an integrated account for the multifactorial origin of honeybee losses and a new framework for assessing, and possibly mitigating, the impact of environmental challenges on honeybee health.

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Schematic diagram of within-host viral copy number (V) and immune currency (I) dynamics.The bold lines represent dynamical processes captured explicitly in equations S4, S5. In this model, the viral population dynamics are governed by two antagonistic processes, replication and control (by the immune system). The immune dynamics are in turn governed by three processes; maintenance (increasing immune stocks), stressors (depleting immune stocks) and a specific impact of virally-mediated immune modification (ranging from excitatory to suppressive). The dotted lines represent processes that are external to the model: 1) over-growth of the virus directly leads to increased bee mortality and collapse of the colony (Figures 1 and 2); 2) despite impending collapse within a focal colony, the virus can escape its host via horizontal transmission facilitated by its mite symbiont [21], [73]; 3) the mite may gain further advantages from its association with an immuno-suppressive virus, as the suppression will further release immunological control of mite feeding; 4) the mite can affect honeybee survival [21].
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ppat-1002735-g007: Schematic diagram of within-host viral copy number (V) and immune currency (I) dynamics.The bold lines represent dynamical processes captured explicitly in equations S4, S5. In this model, the viral population dynamics are governed by two antagonistic processes, replication and control (by the immune system). The immune dynamics are in turn governed by three processes; maintenance (increasing immune stocks), stressors (depleting immune stocks) and a specific impact of virally-mediated immune modification (ranging from excitatory to suppressive). The dotted lines represent processes that are external to the model: 1) over-growth of the virus directly leads to increased bee mortality and collapse of the colony (Figures 1 and 2); 2) despite impending collapse within a focal colony, the virus can escape its host via horizontal transmission facilitated by its mite symbiont [21], [73]; 3) the mite may gain further advantages from its association with an immuno-suppressive virus, as the suppression will further release immunological control of mite feeding; 4) the mite can affect honeybee survival [21].

Mentions: The key immune currency identified by our transcriptome analysis is a member of NF-κB gene family. This gene family not only plays a central role in insect immunity [69], but is also involved in intricate cross-talks with a number of physiological and stress response pathways, conserved across different organisms [55], which are often reciprocally tuned to allow optimal energy allocation between metabolism and immune response, as recently demonstrated in Drosophila[70]; the observed induction of DWV replication in bees exposed to cold stress [50] seems to lend further support to this hypothesis. Therefore, different stress factors impacting immunity and metabolism may compete for the use of NF-κB cellular pools, already reduced by the parasite-pathogen association, promoting intense viral replication in bees harbouring silent infections and subsequent colony collapse (Figure 7). The considerable diversity of stress factors that can interfere with the immune system may partly account for the variety of putative causal agents invoked so far to explain honeybee colony losses, that do not seem to be univocally linked to a specific causative agent.


Synergistic parasite-pathogen interactions mediated by host immunity can drive the collapse of honeybee colonies.

Nazzi F, Brown SP, Annoscia D, Del Piccolo F, Di Prisco G, Varricchio P, Della Vedova G, Cattonaro F, Caprio E, Pennacchio F - PLoS Pathog. (2012)

Schematic diagram of within-host viral copy number (V) and immune currency (I) dynamics.The bold lines represent dynamical processes captured explicitly in equations S4, S5. In this model, the viral population dynamics are governed by two antagonistic processes, replication and control (by the immune system). The immune dynamics are in turn governed by three processes; maintenance (increasing immune stocks), stressors (depleting immune stocks) and a specific impact of virally-mediated immune modification (ranging from excitatory to suppressive). The dotted lines represent processes that are external to the model: 1) over-growth of the virus directly leads to increased bee mortality and collapse of the colony (Figures 1 and 2); 2) despite impending collapse within a focal colony, the virus can escape its host via horizontal transmission facilitated by its mite symbiont [21], [73]; 3) the mite may gain further advantages from its association with an immuno-suppressive virus, as the suppression will further release immunological control of mite feeding; 4) the mite can affect honeybee survival [21].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3375299&req=5

ppat-1002735-g007: Schematic diagram of within-host viral copy number (V) and immune currency (I) dynamics.The bold lines represent dynamical processes captured explicitly in equations S4, S5. In this model, the viral population dynamics are governed by two antagonistic processes, replication and control (by the immune system). The immune dynamics are in turn governed by three processes; maintenance (increasing immune stocks), stressors (depleting immune stocks) and a specific impact of virally-mediated immune modification (ranging from excitatory to suppressive). The dotted lines represent processes that are external to the model: 1) over-growth of the virus directly leads to increased bee mortality and collapse of the colony (Figures 1 and 2); 2) despite impending collapse within a focal colony, the virus can escape its host via horizontal transmission facilitated by its mite symbiont [21], [73]; 3) the mite may gain further advantages from its association with an immuno-suppressive virus, as the suppression will further release immunological control of mite feeding; 4) the mite can affect honeybee survival [21].
Mentions: The key immune currency identified by our transcriptome analysis is a member of NF-κB gene family. This gene family not only plays a central role in insect immunity [69], but is also involved in intricate cross-talks with a number of physiological and stress response pathways, conserved across different organisms [55], which are often reciprocally tuned to allow optimal energy allocation between metabolism and immune response, as recently demonstrated in Drosophila[70]; the observed induction of DWV replication in bees exposed to cold stress [50] seems to lend further support to this hypothesis. Therefore, different stress factors impacting immunity and metabolism may compete for the use of NF-κB cellular pools, already reduced by the parasite-pathogen association, promoting intense viral replication in bees harbouring silent infections and subsequent colony collapse (Figure 7). The considerable diversity of stress factors that can interfere with the immune system may partly account for the variety of putative causal agents invoked so far to explain honeybee colony losses, that do not seem to be univocally linked to a specific causative agent.

Bottom Line: The de-stabilisation of DWV infection is associated with an immunosuppression syndrome, characterized by a strong down-regulation of the transcription factor NF-κB.The centrality of NF-κB in host responses to a range of environmental challenges suggests that this transcription factor can act as a common currency underlying colony collapse that may be triggered by different causes.Our results offer an integrated account for the multifactorial origin of honeybee losses and a new framework for assessing, and possibly mitigating, the impact of environmental challenges on honeybee health.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Scienze Agrarie e Ambientali, Università degli Studi di Udine, Udine, Italy. francesco.nazzi@uniud.it

ABSTRACT
The health of the honeybee and, indirectly, global crop production are threatened by several biotic and abiotic factors, which play a poorly defined role in the induction of widespread colony losses. Recent descriptive studies suggest that colony losses are often related to the interaction between pathogens and other stress factors, including parasites. Through an integrated analysis of the population and molecular changes associated with the collapse of honeybee colonies infested by the parasitic mite Varroa destructor, we show that this parasite can de-stabilise the within-host dynamics of Deformed wing virus (DWV), transforming a cryptic and vertically transmitted virus into a rapidly replicating killer, which attains lethal levels late in the season. The de-stabilisation of DWV infection is associated with an immunosuppression syndrome, characterized by a strong down-regulation of the transcription factor NF-κB. The centrality of NF-κB in host responses to a range of environmental challenges suggests that this transcription factor can act as a common currency underlying colony collapse that may be triggered by different causes. Our results offer an integrated account for the multifactorial origin of honeybee losses and a new framework for assessing, and possibly mitigating, the impact of environmental challenges on honeybee health.

Show MeSH
Related in: MedlinePlus