Zika virus infection drives epigenetic modulation of immunity by the histone acetyltransferase CBP of Aedes aegypti

PLoS Negl Trop Dis. 2022 Jun 27;16(6):e0010559. doi: 10.1371/journal.pntd.0010559. eCollection 2022 Jun.


Epigenetic mechanisms are responsible for a wide range of biological phenomena in insects, controlling embryonic development, growth, aging and nutrition. Despite this, the role of epigenetics in shaping insect-pathogen interactions has received little attention. Gene expression in eukaryotes is regulated by histone acetylation/deacetylation, an epigenetic process mediated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, we explored the role of the Aedes aegypti histone acetyltransferase CBP (AaCBP) after infection with Zika virus (ZIKV), focusing on the two main immune tissues, the midgut and fat body. We showed that the expression and activity of AaCBP could be positively modulated by blood meal and ZIKV infection. Nevertheless, Zika-infected mosquitoes that were silenced for AaCBP revealed a significant reduction in the acetylation of H3K27 (CBP target marker), followed by downmodulation of the expression of immune genes, higher titers of ZIKV and lower survival rates. Importantly, in Zika-infected mosquitoes that were treated with sodium butyrate, a histone deacetylase inhibitor, their capacity to fight virus infection was rescued. Our data point to a direct correlation among histone hyperacetylation by AaCBP, upregulation of antimicrobial peptide genes and increased survival of Zika-infected-A. aegypti.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aedes* / genetics
  • Animals
  • Epigenesis, Genetic
  • Histone Acetyltransferases / genetics
  • Histones / genetics
  • Mosquito Vectors
  • Zika Virus Infection*
  • Zika Virus* / physiology


  • Histones
  • Histone Acetyltransferases

Grants and funding

This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (470099/20143) and Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (E-26/202990/2015) to MRF. PLO was supported by Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (573959/2008-0). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.