Altered histone modifications in Aedes aegypti midguts following Rift Valley fever virus exposure.

When arthropod-borne viruses (arboviruses) are delivered to vector mosquitoes in infectious bloodmeals, viral components interact with host proteins to hijack cells and initiate replication. The extent to which arbovirus infection alters mosquito host transcriptional regulatory processes is currently unknown. We hypothesized that histone modifications would be altered in mosquitoes exposed to Rift Valley fever virus (RVFV MP12). H3K27ac and H3K9me3 marks were interrogated using CUT&RUN in a mosquito species that has a predicted dissemination barrier, Aedes aegypti. Global H3K27ac peaks showed progressive depletion over time compared to bloodfed controls. Gene set enrichment analysis revealed that immune response transcripts were enriched at 1 and 3 days post-feeding (dpf). For virus-exposed samples, the highest proportion of DEGs proximal to histone marks occurred with depletion of repressive H3K9me3 peaks at 3 dpf. Associated DEGs included transcription factors, secondary messengers and processes affecting cell polarization. Analysis of midguts after a non-infectious bloodmeal versus sugar-fed controls revealed global changes to H3K27ac and H3K9me3 marks, as well. Differential H3K27ac marks were proximal to one quarter of all DEGs at 1 dpf, consistent with an important role of H3K27ac in bloodmeal digestion. Together, these results demonstrate that H3K27ac and H3K9me3 patterns are altered upon virus exposure in a complex interplay that could be due to viral manipulation or host defense.