Document Type

Article

Publication Date

2025

DOI

10.1371/journal.pone.0319290

Publication Title

PLoS ONE

Volume

20

Issue

2

Pages

e0319290 (1-18)

Abstract

Zika virus (ZIKV) is a mosquito-borne human pathogen that causes mild febrile illness in adults and severe neurological complications and microcephaly in newborns. Studies have reported that ZIKV modulates methylation of human and viral RNA critical for its replication in vertebrate cells. In this study, we show that ZIKV modulates mosquito S-adenosyl methionine (SAMe)-synthase, an enzyme involved in the production of SAMe (methyl donor), and histone methylation for its survival in mosquito cells. Reverse transcription quantitative PCR followed by immunoblotting analysis showed increased amounts of SAMe synthase at both RNA and protein levels, respectively, in C6/36 mosquito cells infected with ZIKV at day 1 post infection (p.i.). Increased levels of SAMe was noted upon ZIKV infection at day 1 p.i in mosquito cells. In addition, increased EZH2 histone methyl transferase-like gene transcripts and methylated histone (H3K27me3) levels were evident in mosquito cells upon ZIKV infection. Exogenous addition of SAMe to mosquito cells showed increased ZIKV loads and EZH2 histone methyl transferase-like gene transcript levels. Furthermore, treatment of mosquito cells with EZH2 inhibitor resulted in reduced histone methylation and ZIKV loads. Collectively, our study provides novel information in understanding the importance of SAMe and histone methylation in the survival of ZIKV in its arthropod vector.

Rights

© 2025 Harrell et al.

This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability

Article states: "All relevant data are within the manuscript and its Supporting Information files."

Original Publication Citation

Harrell, T., Basak, S., Sultana, H., & Neelakanta, G. (2025). Zika virus modulates arthropod histone methylation for its survival in mosquito cells. PLoS One, 20(2), 1-18, Article e0319290. https://doi.org/10.1371/journal.pone.0319290

ORCID

0000-0002-9882-2584 (Harrell)

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