Varroa destructor parasitism has a greater effect on proteome changes than the deformed wing virus and activates TGF-\u03b2 signaling pathways

Tomas Erban,Klara Kadlikova,Bruno Sopko,Karel Harant,Pavel Talacko

doi:10.1038/s41598-019-45764-1

Abstract

Honeybee workers undergo metamorphosis in capped cells for approximately 13 days before adult emergence. During the same period, Varroa mites prick the defenseless host many times. We sought to identify proteome differences between emerging Varroa-parasitized and parasite-free honeybees showing the presence or absence of clinical signs of deformed wing virus (DWV) in the capped cells. A label-free proteomic analysis utilizing nanoLC coupled with an Orbitrap Fusion Tribrid mass spectrometer provided a quantitative comparison of 2316 protein hits. Redundancy analysis (RDA) showed that the combination of Varroa parasitism and DWV clinical signs caused proteome changes that occurred in the same direction as those of Varroa alone and were approximately two-fold higher. Furthermore, proteome changes associated with DWV signs alone were positioned above Varroa in the RDA. Multiple markers indicate that Varroa activates TGF-β-induced pathways to suppress wound healing and the immune response and that the collective action of stressors intensifies these effects. Furthermore, we indicate JAK/STAT hyperactivation, p53-BCL-6 feedback loop disruption, Wnt pathway activation, Wnt/Hippo crosstalk disruption, and NF-κB and JAK/STAT signaling conflict in the Varroa–honeybee–DWV interaction. These results illustrate the higher effect of Varroa than of DWV at the time of emergence. Markers for future research are provided.

Highlights

Since Varroa destructor (Anderson & Trueman, 2000) shifted from the eastern honeybee, Apis cerana Fabricius, 1793, to the western honeybee, Apis mellifera Linnaeus, 1758, this mite has become one of the most important factors in colony loss, and Varroa parasitism is strongly connected to viral transmission within and between colonies
This study provides the basis for understanding the effects of Varroa parasitism, including deformed wing virus (DWV), over metamorphosis in capped cells at the molecular level
We suggest the interesting idea that the marker tprx1/BCL-6c represses BCL-655, thereby facilitating the activity of Stat5B, but the function of the putative BCL-6c must be investigated in future analyses

Summary

Introduction

Since Varroa destructor (Anderson & Trueman, 2000) shifted from the eastern honeybee, Apis cerana Fabricius, 1793, to the western honeybee, Apis mellifera Linnaeus, 1758, this mite has become one of the most important factors in colony loss, and Varroa parasitism is strongly connected to viral transmission within and between colonies. Diverse pathogenic viruses have been identified in honeybees, the most common and most well-studied is the deformed wing virus (DWV), for which increases in load with mite infestation have been thoroughly documented in honeybee colonies. The impact of the mite on the bee should be more substantial at the time of adult emergence than in the red/purple-eye pupa stage. It can be proposed that the principle mechanisms underlying the Varroa–honeybee–DWV interaction should be similar to those established for tick–host–pathogen interactions Both ticks and pathogens manipulate their hosts, but their mutual impact results in both conflict and cooperation[19]. The molecular mechanisms that provide evidence of the Varroa–honeybee–DWV interaction are puzzling compared to those in the tick–host–pathogen interaction

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Results