Dengue Virus Exploits the Host TRNA Epitranscriptome to Promote Viral Replication

Overview

Journal bioRxiv

Date 2023 Nov 21

PMID 37986976

Authors

Cheryl Chan

Newman Siu Kwan Sze

Yuka Suzuki

Takayuki Ohira

Tsutomu Suzuki

Thomas J Begley

Peter C Dedon

Affiliations

Soon will be listed here.

Abstract

The 40-50 RNA modifications of the epitranscriptome regulate posttranscriptional gene expression. Here we show that flaviviruses hijack the host tRNA epitranscriptome to promote expression of pro-viral proteins, with tRNA-modifying ALKBH1 acting as a host restriction factor in dengue virus infection. Early in the infection of human Huh-7 cells, ALKBH1 and its tRNA products 5-formylcytidine (fC) and 2'--methyl-5-formylcytidine (fCm) were reduced. ALKBH1 knockdown mimicked viral infection, but caused increased viral NS3 protein levels during infection, while ALKBH1 overexpression reduced NS3 levels and viral replication, and increased fC and fCm. Viral NS5, but not host FTSJ1, increased fCm levels late in infection. Consistent with reports of impaired decoding of leucine UUA codon by fCm-modified tRNA, ALKBH1 knockdown induced translation of UUA-deficient transcripts, most having pro-viral functions. Our findings support a dynamic ALKBH1/fCm axis during dengue infection, with virally-induced remodeling of the proteome by tRNA reprogramming and codon-biased translation.

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