Transcriptomic and Epigenomic Dynamics of Honey Bees in Response to Lethal Viral Infection

Abstract

Honey bees (Apis mellifera L.) suffer from many brood pathogens, including viruses. Despite considerable research, the molecular responses and dynamics of honey bee pupae to viral pathogens remain poorly understood. Israeli Acute Paralysis Virus (IAPV) is emerging as a model virus since its association with severe colony losses. Using worker pupae, we studied the transcriptomic and methylomic consequences of IAPV infection over three distinct time points after inoculation. Contrasts of gene expression and 5 mC DNA methylation profiles between IAPV-infected and control individuals at these time points-corresponding to the pre-replicative (5 h), replicative (20 h), and terminal (48 h) phase of infection-indicate that profound immune responses and distinct manipulation of host molecular processes accompany the lethal progression of this virus. We identify the temporal dynamics of the transcriptomic response to with more genes differentially expressed in the replicative and terminal phases than in the prereplicative phase. However, the number of differentially methylated regions decreased dramatically from the pre-replicative to the replicative and terminal phase. Several cellular pathways experienced hyper-and hypo-methylation in the pre-replicative phase and later dramatically increased in gene expression at the terminal phase, including the MAPK, Jak-STAT, Hippo, mTOR, TGF-beta signaling pathways, ubiquitin mediated proteolysis, and spliceosome. These affected biological functions suggest that adaptive host responses to combat the virus are mixed with viral manipulations of the host to increase its own reproduction, all of which are involved in anti-viral immune response, cell growth, and proliferation. Comparative genomic analyses with other studies of viral infections of honey bees and fruit flies indicated that similar immune pathways are shared. Our results further suggest that dynamic DNA methylation responds to viral infections quickly, regulating subsequent gene activities. Our study provides new insights of molecular mechanisms involved in epigenetic that can serve as foundation for the long-term goal to develop anti-viral strategies for honey bees, the most important commercial pollinator.

Phenotypic Plasticity: What Has DNA Methylation Got to Do with It?

“…DNA methylation may also mark a sub-set of genes allowing them to be 'poised' for later gene expression, as has been documented for a histone modification in the honeybee [70]. Two recent studies in honeybees have hinted that changes in DNA methylation may precede changes in gene expression [68,71]; although, neither showed a direct or causal association between differences in DNA methylation and differences of gene expression.…”

“…While studies of genome-wide DNA methylation patterns have not indicated a key role in regulating developmental plasticity, many studies have shown that DNA methylation in insects changes under a variety of environmental conditions, such as parasitism [87], photoperiod [88] and immune challenges, e.g., [71].…”

Peptidoglycan recognition protein S2 is crucial for activation the Toll pathway against Israeli acute paralysis virus infection in honey bee Apis mellifera

“…For example, most of up-and downstream genes of the [19]. Also transcriptomic analyses from Li-Byarlay et al have suggested that the Toll/Imd pathway was significantly enriched in IAPVinfected pupae [20]. However, Chen et al found that multiple immune biological pathways were significantly up-regulated, especially Jak-STAT pathway [17], which was no different in brood but significantly invoked in adult bees.…”

Caste- and sex-specific DNA methylation in a bumblebee is associated with codon degeneracy

“…Genes which show parent-of-origin expression have been identified in two social insect species to date, B. terrestris (Marshall et al ., 2020b) and A. mellifera (Wu et al ., 2020). Whilst a direct link between parent-of-origin DNA methylation and parent-of-origin expression has not been found in the honeybee (Wu et al ., 2020; Smith et al ., 2020), it is possible parent-of-origin DNA methylation may mediate imprinted genes in a trans- or temporal-acting fashion (Xu et al ., 2021; Li-Byarlay et al ., 2020). For example, in mammals DNA methylation can act to silence an imprinting control element, which when normally expressed would silence nearby genes (Barlow, 2011).…”